Podcasts about Trypanosoma

TWiP explains a study which finds that tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei, then remembers our departed colleague Dickson Despommier. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Click arrow to play Download TWiP #254 (88 MB .mp3, 61 minutes) Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Tissue spaces are reservoirs of antigenic diversity for T. brucei (Nature) Understanding trypanosome antigenic variation (Emerg Top Life Sci) Tissue resident T. brucei (PLoS Path) Hero – Dickson Despommier Despommier Photo Art Parasitology Course (YouTube) Become a patron of TWiP  Send your questions and comments to twip@microbe.tv Music by Ronald Jenkees TWiP explains a study which finds that tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei, then remembers our departed colleague Dickson Despommier. Hosts: Vincent Racaniello, Daniel Griffin, and Christina Naula Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Tissue spaces are reservoirs of antigenic diversity for T. brucei (Nature) Understanding trypanosome antigenic variation (Emerg Top Life Sci) Tissue resident T. brucei (PLoS Path) Hero – Dickson Despommier Despommier Photo Art Parasitology Course (YouTube) Become a patron of TWiP  Send your questions and comments to twip@microbe.tv Music by Ronald Jenkees

Lauren and JJ welcome veterinary neurologist Dr. Jill Narak to the podcast to discuss brain-eating and brain-hijacking (zombie!) diseases. Resources: * IMDB entry for The Return of the Living Dead (1985), directed by Dan O'Bannon: https://www.imdb.com/title/tt0089907/ * Behavior-altering parasites, Wikipedia, accessed 10/26/24: https://en.m.wikipedia.org/wiki/Behavior-alteringparasite * Naegleria fowleri infection, Centers for Disease Control, accessed 10/26/24: https://www.cdc.gov/naegleria/about/index.html * Transmissible spongiform encephalopathies, National Institute of Neurological Disorders and Stroke, accessed 10/26/24: https://www.cdc.gov/naegleria/about/index.html * Echinococcosis, Centers for Disease Control, accessed 10/26/24: https://www.cdc.gov/naegleria/about/index.html * Siyadatpanah, A., et al. Cerebral cystic echinococcosis (2020). Case reports in infectious diseases. https://pmc.ncbi.nlm.nih.gov/articles/PMC7066420/ * Heyward, G. The zombie fungus from 'The Last of Us' is real - but not nearly as deadly (2023), NPR, last accessed 10/26/24: https://www.npr.org/2023/01/30/1151868673/the-last-of-us-cordyceps-zombie-fungus-real# * Flegr, J. Effects of _Toxoplasma on human behavior (2007). Schizophrenia bulletin, 33(3): 757-760. https://pmc.ncbi.nlm.nih.gov/articles/PMC2526142/ * Adebiyi, O. E., et al. Neurocognitive domains and neuropathological changes in experimental infection with Trypanosoma brucei brucei in Wister rats (2021). Heliyon, 7(11). https://pmc.ncbi.nlm.nih.gov/articles/PMC8571699/ * Alvarado-Esquivel. Toxocara infection in psychiatric inpatients: A case control seroprevalence study (2013). PLoS One, 8(4). https://pmc.ncbi.nlm.nih.gov/articles/PMC3633879/ * Horsehair worm. The Wildlife Trusts, accessed 10/26/24. https://www.wildlifetrusts.org/wildlife-explorer/marine/worms/horsehair-worm# * Gasque, S. N., et al. Where the baculoviruses lead, the caterpillars follow: baculovirus-induced alterations in caterpillar behavior (2019). Current opinion in insect science, 33: 30-36. https://www.sciencedirect.com/science/article/abs/pii/S2214574518300841# * Clinical Overview of Rabies, Centers for Disease Control, accessed 10/26/24: https://www.cdc.gov/rabies/hcp/clinical-overview/index.html * Zombie, Wikipedia, accessed 10/26/24: https://en.wikipedia.org/wiki/Zombie Special Guest: Jill Narak.

Estamos ON! No episódio #94 do CienciON, mergulhamos fundo na Doença de Chagas com o Professor João Henrique Ghilardi Lago (UFABC), um expert que vai descomplicar tudo sobre essa doença negligenciada, mas que afeta milhões de pessoas na América Latina. Se você quer entender os desafios da prevenção, diagnóstico e tratamento dessa doença, este episódio é para você! CienciON #94: Série “É doença demais” – Doença de Chagas Este episódio faz parte da série "É Doença Demais", onde discutimos doenças que têm um grande impacto na saúde pública, mas que muitas vezes não recebem a atenção devida. CienciON#94: Doença de Chagas Roteiro de: Giuliana Moreira Celestino (UFABC) Convidado: Prof. João Henrique Ghilardi Lago (UFABC), que vai explorar desde a biologia do Trypanosoma cruzi, o parasita causador da doença, até as estratégias atuais para controle e tratamento. Edição de áudio: André Luis Penha da Silva (UFABC), garantindo que cada detalhe da nossa conversa chegue até você com a melhor qualidade. Participantes: Prof. Pedro Autreto (UFABC) Revisão: Prof. Pedro Autreto e Prof. João Henrique Ghilardi Lago (UFABC), para garantir a precisão e clareza das informações apresentadas. Edição de arte (capa): Prof. Pedro Autreto, criando uma identidade visual que capta a essência do episódio. Divulgação e mídias: Giuliana Moreira Celestino (UFABC), responsável por conectar este conteúdo com você através das redes sociais e outros canais. Coordenação Geral: Prof. Pedro Autreto (UFABC), unindo todos os elementos para entregar um episódio informativo e envolvente. Agradecimentos: Pró-Reitoria de Extensão e Cultura (PROEC) da UFABC pelo apoio contínuo na disseminação do conhecimento. #CienciON #DoençaDeChagas #UFABC #SaúdePública #CiênciaParaTodos #Educação #ExtensãoUniversitária #DivulgaçãoCientífica #Pesquisa #Conhecimento #Podcast #DoençasNegligenciadas #TrypanosomaCruzi #Prevenção #Tratamento

Michael Barrett joins TWiP to discuss progress in the elimination of human African trypanosomiasis caused by Trypanosoma brucei gambiense. Hosts: Daniel Griffin, Dickson Despommier and Christina Naula Guest: Michael Barrett Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode Join the MicrobeTV Discord server Elimination of human African trypanosomiasis (PLoS NTD) Hero: David Livingstone Become a patron of TWiP  Send your guesses to twip@microbe.tv with TWiP 237 in the subject line Send your questions and comments to twip@microbe.tv Music by Ronald Jenkees

Bell2Bell's latest podcast features Dr. Marshal Lemerani, Program Manager for the Malawi Ministry of Health and Howard Weisman, CEO of PaxMedica (NASDAQ: PXMD), a biopharmaceutical company dedicated to advancing treatments for neurological disorders, which takes center stage in the episode. During this insightful conversation, Howard Weisman, CEO of PaxMedica, and Dr. Marshal Lemerani, Program Manager at the Malawi Ministry of Health, joined host Stuart Smith to discuss the urgent request for medical assistance from Malawi and PaxMedica's swift response. The podcast sheds light on PaxMedica's commitment to addressing the critical shortage of medications required to combat the life-threatening sleeping sickness crisis in Malawi. Weisman highlights the pressing need for IV suramin (PAX-101), a crucial medication in treating Trypanosoma brucei rhodesiense Human African trypanosomiasis (TBr HAT), and PaxMedica's immediate action plan to aid. Lemerani shares insights into the challenges faced by healthcare professionals in Malawi and expresses gratitude for PaxMedica's support in this dire situation. To listen to the full podcast and learn more about PaxMedica's response to the urgent medical situation in Malawi, visit https://podcast.bell2bell.com. The latest installment of The Bell2Bell Podcast continues to reinforce IBN's commitment to the expansion of its robust network of brands, client partners, followers, and the growing IBN Podcast Series. For more than 18 years, IBN has leveraged this commitment to provide unparalleled distribution and corporate messaging solutions to 500+ public and private companies.

Bell2Bell's latest podcast features Dr. Marshal Lemerani, Program Manager for the Malawi Ministry of Health and Howard Weisman, CEO of PaxMedica (NASDAQ: PXMD), a biopharmaceutical company dedicated to advancing treatments for neurological disorders, which takes center stage in the episode. During this insightful conversation, Howard Weisman, CEO of PaxMedica, and Dr. Marshal Lemerani, Program Manager at the Malawi Ministry of Health, joined host Stuart Smith to discuss the urgent request for medical assistance from Malawi and PaxMedica's swift response. The podcast sheds light on PaxMedica's commitment to addressing the critical shortage of medications required to combat the life-threatening sleeping sickness crisis in Malawi. Weisman highlights the pressing need for IV suramin (PAX-101), a crucial medication in treating Trypanosoma brucei rhodesiense Human African trypanosomiasis (TBr HAT), and PaxMedica's immediate action plan to aid. Lemerani shares insights into the challenges faced by healthcare professionals in Malawi and expresses gratitude for PaxMedica's support in this dire situation. To listen to the full podcast and learn more about PaxMedica's response to the urgent medical situation in Malawi, visit https://podcast.bell2bell.com. The latest installment of The Bell2Bell Podcast continues to reinforce IBN's commitment to the expansion of its robust network of brands, client partners, followers, and the growing IBN Podcast Series. For more than 18 years, IBN has leveraged this commitment to provide unparalleled distribution and corporate messaging solutions to 500+ public and private companies.  

Professor Koos van der Hoeven spreekt met professor Piet Borst naar aanleiding van de toekenning aan hem van de Lasker-Koshland Special Achievement Award in Medical Science. Aan bod komen onder andere zijn onderzoek naar Trypanosoma, multiple-drugresistentie, zijn functie als wetenschappelijk directeur bij het Antoni van Leeuwenhoek waar hij tot op heden actief is en de doorbraken in het onderzoek naar kanker. En tot slot ook nog een woord over de Nederlandse Vereniging tegen de kwakzalverij.

Michelle and Alexander join TWiP to solve their case of the 36 Year Old Male with shortness of breath, stinging pain in the extremities, fatigue, abdominal cramps, and bowel irregularities, and discuss host cell invasion by Trypanosoma cruzi. Hosts: Vincent Racaniello, Dickson Despommier, Daniel Griffin, and Christina Naula Guests: Michelle Naegeli and Alexander Grieb Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Links for this episode cAMP-dependent invasion by Trypanosoma cruzi (PLoS NTDS) Letters read on TWiP 220 Become a patron of TWiP Case Study for TWiP 221 This is the case of a  man in his 50s, with no remarkable prior medical history, who received care at a hospital in northern California, USA, after experiencing a generalized seizure. Magnetic resonance imaging (MRI) demonstrated a solitary left temporal lobe T2 hyperintensity with gadolinium rim enhancement and surrounding edema. After receiving treatment with dexamethasone and levetiracetam, he was transferred to an academic medical center. Examination by neurology consultants noted disorientation, inattention, moderate aphasia (difficulty communicating), and mild right hemiparesis. Cerebrospinal fluid (CSF) testing revealed increased nucleated cells up to 80/UL (60% lymphocytes, 17% neutrophils, 23% monocytes), protein concentration 38 mg/dL, and glucose concentration 100 mg/dL.  They proceed to do a brain biopsy from the left temporal lobe lesion with cultures from the brain biopsy sample that did not grow bacteria, fungi, or mycobacteria. They performed metagenomic next-generation sequencing (mNGS) on a CSF sample and sent brain biopsy samples for universal broad-range PCR amplicon sequencing (uPCR) for bacteria, fungi, Mycobacterium tuberculosis, and nontuberculous mycobacteria. which is preliminarily reported as showing well-formed granulomata with acute inflammation. Rereview of neuropathology raised concern for certain round infectious forms that are about 50um in size with some surrounding clearing and a dark area within these forms. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.07.548172v1?rss=1 Authors: Darden, C., Donkor, J. E., Korolkova, O., Khan Barozai, M. Y., Chaudhuri, M. Abstract: Nuclear-encoded mitochondrial proteins are correctly translocated to their proper sub-mitochondrial destination using location specific mitochondrial targeting signals (MTSs) and via multi-protein import machineries (translocases) in the outer and inner mitochondrial membranes (TOM and TIMs, respectively). However, MTSs of multi-pass Tims are less defined. Here we report the characterization of the MTSs of Trypanosoma brucei Tim17 (TbTim17), an essential component of the most divergent TIM complex. TbTim17 possesses a characteristic secondary structure including four predicted transmembrane (TM) domains in the center with hydrophilic N- and C- termini. After examining mitochondrial localization of various deletion and site-directed mutants of TbTim17 in T. brucei using subcellular fractionation and confocal microscopy we located at least two internal signals, 1) within TM1 (31-50 AAs) and 2) TM4 + Loop 3 (120-136 AAs). Both signals are required for proper targeting and integration of TbTim17 in the membrane. Furthermore, a positively charged residue (K122) is critical for mitochondrial localization of TbTim17. This is the first report of characterizing the internal mitochondrial targeting signals (ITS) for a multipass inner membrane protein in a divergent eukaryote, like T. brucei. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

En la Universidad Nacional de San Luis avanzan en una investigación cuyo objetivo es crear un prototipo de vacuna contra el Chagas. Es un proyecto multidisciplinario de expertos de diversos países que trabajan en lograr desarrollos contra la enfermedad causada por el parásito Trypanosoma cruzi encontrado en las heces de la vinchuca. Lo explica la Dra. María Marta Branda, investigadora del Conicet, docente universitaria y científica UNSL.

This month on Episode 48 of Discover CircRes, host Cynthia St. Hilaire highlights three original research articles featured in the April 28th issue of Circulation Research. This Episode also includes a discussion between Dr Mina Chung, Dr DeLisa Fairweather and Dr Milka Koupenova, who all contributed to manuscripts to the May 12th Compendium on Covid-19 and the Cardiovascular System.     Article highlights:   Heijman, et al. Mechanisms of Enhanced SK-Channel Current in AF   Chen, et al. IL-37 Attenuates Platelet Activation   Enzan, et al. ZBP1 Protects Against Myocardial Inflammation   Compendium on Covid-19 and the Cardiovascular System.   Cindy St. Hilaire: Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. Today, I'm going to be highlighting articles from our April 28th and May 12th issues of Circulation Research. I'm also going to have a chat with Dr Mina Chung, Dr DeLisa Fairweather and Dr Milka Koupenova, who all contributed to articles in the May 12th COVID Compendium. But before we have that interview, let's first talk about some highlights.   The first article I want to present is titled Enhanced Calcium-Dependent SK-Channel Gating and Membrane Trafficking in Human Atrial Fibrillation. This article is coming from the University of Essen by Heijman and Zhou, et al. Atrial fibrillation is one of the most common forms of heart arrhythmia in humans and is characterized by irregular, often rapid heartbeats that can cause palpitations, dizziness and extreme fatigue. Atrial fibrillation can increase a person's risk of heart failure, and though treatments exist such as beta blockers, blood thinners and antiarrhythmia medications, they can have limited efficacy and side effects. A new family of drugs in development are those blocking small-conductance calcium-activated potassium channels called SK channels, which exhibit increased activity in animal models of AF and suppression of which attenuates the arrhythmia. In humans however, the relationship between SK channels and atrial fibrillation is less clear, at least in terms of SK channel mRNA levels. Because mRNA might not reflect actual channel activity, this group looked at just that and they found indeed that channel activity was increased in cardiomyocytes from atrial fibrillation patients compared to those from controls even though the mRNA and protein levels themselves were similar. The altered currents were instead due to changes in SK channel trafficking and membrane targeting. By confirming that SK channels play a role in human atrial fibrillation, this work supports the pursuit of SK channel inhibitors as possible new atrial fibrillation treatments.   The next article I want to present is titled IL-37 Attenuates Platelet Activation and Thrombosis Through IL-1R8 Pathway. This article comes from Fudan University by Chen and Hong, et al. Thrombus formation followed by the rupture of a coronary plaque is a major pathophysiological step in the development of a myocardial infarction. Understanding the endogenous antithrombotic factors at play could provide insights and opportunities for developing treatments. With this in mind, Chen and Hong, et al. investigated the role of interleukin-1 receptor 8, or IL-1R8, which suppresses platelet aggregation in mice, and of IL-37, a newly discovered human interleukin that forms a complex with IL-1R8 and is found at increased levels in the blood of patients with myocardial infarction. Indeed, the amount of IL-37 in myocardial infarction patients negatively correlates with platelet aggregation. They also show that treatment of human platelets in vitro with IL-37 suppresses the cell's aggregation and does so in a concentration-dependent manner. Moreover, injection of the protein into the veins of mice inhibits thrombus development and better preserves heart function even after myocardial infarction. Such effects were not seen in mice lacking IL-1R8. This suggests IL-37's antithrombotic action depends on its interaction with the receptor. Together, the results suggest IL-37 could be developed as a antithrombotic agent for use in MI patients or indeed perhaps other thrombotic conditions.   The last article I want to present before our interview is titled ZBP1 Protects Against Mitochondrial DNA-Induced Myocardial Inflammation in Failing Hearts. This article is coming from Kyushu University and is by Enzan, et al. Myocardial inflammation is a key factor in the pathological progression of heart failure and occurs when damaged mitochondria within the stricken cardiomyocyte release their DNA, triggering an innate inflammatory reaction. In a variety of cells, DNA sensors such as Z-DNA-binding protein 1 or ZBP1 are responsible for such mitochondrial DNA-induced inflammation. In theory then, it's conceivable that therapeutic suppression of ZBP1 might reduce myocardial inflammation in heart failure and preserve function. But as Enzan and colleagues have now discovered to their surprise, mice lacking ZBP1 exhibited worse, not better heart inflammation and more failure after induced myocardial infarction. Indeed, the test animals' hearts had increased infiltration of immune cells, production of inflammatory cytokines and fibrosis together with decreased function compared with the hearts of mice with normal ZBP1 levels. Experiments in rodent cardiomyocytes further confirmed that loss of ZBP1 exacerbated mitochondrial DNA-induced inflammatory cytokine production while overexpression of ZBP1 had the opposite effect. While the reason behind ZBP1's opposing roles in different cells is not yet clear, the finding suggests that boosting ZBP1 activity in the heart might be a strategy for mitigating heart inflammation after infarction.   Cindy St. Hilaire:         The May 12th issue of Circulation Research is our COVID compendium, which consists of a series of 10 reviews on all angles of COVID-19 as it relates to cardiovascular health and disease. Today, three of the authors of the articles in this series are here with me. Dr Mina Chung is a professor of medicine at the Cleveland Clinic. She and Dr Tamanna Singh and their colleagues wrote the article, A Post Pandemic Enigma: The Cardiovascular Impact of Post-Acute Sequelae of SARS-CoV-2. Dr DeLisa Fairweather, professor of medicine, immunology and clinical and translational science at the Mayo Clinic, and she and her colleagues penned the article, COVID-19 Myocarditis and Pericarditis. Dr Milka Koupenova is an assistant professor of medicine at the UMass Chan School of Medical and she led the group writing the article, Platelets and SARS-CoV-2 During COVID-19: Immunity, Thrombosis, and Beyond. Thank you all for joining me today.   DeLisa Fairweather:    Thank you so much for having us.   Mina Chung:   Thank you.   Milka Koupenova:       Thank you for having us, Cindy.   Cindy St. Hilaire:         In addition to these three articles, we have another seven that are on all different aspects of COVID. Dr Messinger's group wrote the article, Interaction of COVID-19 With Common Cardiovascular Disorders. Emily Tsai covered cell-specific mechanisms in the heart of COVID-19 patients. Mark Chappell and colleagues wrote about the renin-angiotensin system and sex differences in COVID-19. Michael Bristow covered vaccination-associated myocarditis and myocardial injury. Jow Loacalzo and colleagues covered repurposing drugs for the treatment of COVID-19 and its cardiovascular manifestations. Dr Stephen Holby covered multimodality cardiac imaging in COVID, and Arun Sharma covered microfluidic organ chips in stem cell models in the fight against COVID-19.   Cindy St. Hilaire          As of today, worldwide, there have been over six hundred million individuals infected with the virus and more than six and a half million have died from COVID-19. In the US, we are about a sixth of all of those deaths. Obviously now we're in 2023, the numbers of individuals getting infected and dying are much, much lower. As my husband read to me this morning, one doctor in Boston was quoted saying, "People are still getting wicked sick." In 75% of deaths, people have had underlying conditions and cardiovascular disease is found in about 60% of all those deaths. In the introduction to the compendium, you mentioned that the remarkable COVID-19 rapid response initiative released by the AHA, which again is the parent organization of Circ Research and this podcast, if I were to guess when that rapid response initiative started, I would've guessed well into the pandemic, but it was actually March 26th, 2020. I know in Pittsburgh, our labs have barely shut down. So how soon after we knew of SARS-CoV-2 and COVID, how soon after that did we know that there were cardiovascular complications?   Mina Chung:               I think we saw cardiovascular complications happening pretty early. We saw troponin increases very early. It was really amazing what AHA did in terms of this rapid response grant mechanism. You mentioned that the RFA was announced, first of all, putting it together by March 26th when we were just shutting down in March was pretty incredible to get even the RFA out. Then the grants were supposed to be submitted by April 6th and there were 750 grants that were put together and submitted. They were all reviewed within 10 days from 150 volunteer reviewers. The notices were distributed April 23rd, less than a month out.   Cindy St. Hilaire:         Amazing.   Mina Chung:               So this is an amazing, you're right, paradigm for grant requests and submissions and reviews.   DeLisa Fairweather:    For myocarditis, reports of that occurred almost immediately coming out of China, so it was incredibly rapid.   Cindy St. Hilaire:         Yeah, and that was a perfect lead up to my next question. Was myocarditis, I guess, the first link or the first clue that this was not just going to be a respiratory infection?   DeLisa Fairweather:    I think myocarditis appearing very early, especially it has a history both of being induced by viruses, but being strongly an autoimmune disease, the combination of both of those, I think, started to hint that something different was going to happen, although a lot of people probably didn't realize the significance of that right away.   Cindy St. Hilaire:         What other disease states, I guess I'm thinking viruses, but anything, what causes myocarditis and pericarditis normally and how unique is it that we are seeing this as a sequelae of COVID?   DeLisa Fairweather:    I think it's not surprising that we find it. Viruses around the world are the primary cause of myocarditis, although in South America, it's the parasite Trypanosoma cruzi. Really, many viruses that also we think target mitochondria, including SARS-CoV-2, have an important role in driving myocarditis. Also, we know that SARS-CoV-1 and MERS also reported myocarditis in those previous infections. We knew about it beforehand that they could cause myocarditis.   Cindy St. Hilaire:        Is it presenting differently in a COVID patient than say those South American patients with the... I forget the name of the organism you said, but does it come quickly or get worse quickly or is it all once you get it, it's the same progression?   DeLisa Fairweather:    Yeah. That's a good question. Basically, what we find is that no matter what the viral infection is, that myocarditis really appears for signs and symptoms and how we treat it identically and we see that with COVID-19. So that really isn't any different.   Cindy St. Hilaire:         Another huge observation that we noticed in COVID-19 patients, which was the increased risk of thrombic outcomes in the patients. Dr Koupenova, Milka, you are a world expert in platelets and viruses and so you and your team were leading the writing of that article. My guess is knowing what you know about platelets and viruses, this wasn't so surprising to you, but could you at least tell us the state of the field in terms of what we knew about viruses and platelets before COVID, before Feb 2020?   Milka Koupenova:       Before Feb 2020, we actually knew that influenza gets inside in platelets. It leads to not directly prothrombotic events, but it would lead to release of complement 3 from them. That complement 3 would actually increase the immunothrombosis by pushing neutrophils to release their DNA, forming aggregates. In cases when you have compromised endothelium and people with underlying conditions, you would expect certain thrombotic outcomes. That, we actually published 2019 and then 2020 hit. The difference between influenza and SARS-CoV-2, they're different viruses. They carry their genome in a different RNA strand. I remember thinking perhaps viruses are getting inside in platelets, but perhaps they do not. So we went through surprising discoveries that it seemed like it is another RNA virus. It also got into platelets. It was a bit hard to tweak things surrounding BSL-3 to tell you if the response was the same. It is still not very clear how much SARS or rather what receptor, particularly when it gets inside would induce an immune response. There are some literature showing the MDA5, but not for sure, may be responsible. But what we found is that once it gets in platelets, it just induces this profound activation of programmed cell death pathways and release of extracellular vesicles and all these prothrombotic, procoagulant form of content that can induce damage around, because platelets are everywhere. So that how it started in 2019 and surprisingly progressed to 2021 or 2020 without the plan of really studying this virus.   Cindy St. Hilaire:         How similar and how different is what you observe in platelets infected, obviously in the lab, so I know it's not exactly the same, but how similar and how different is it between the flu? Do you know all the differences yet?   Milka Koupenova:       No offense here, they don't get infected.   Cindy St. Hilaire:         Okay.   Milka Koupenova:       Done the proper research. The virus does not impact platelets, but induces the response.   Cindy St. Hilaire:         Okay.   Milka Koupenova:       That goes back to sensing mechanism. Thank goodness platelets don't get infected because we would be in a particularly bad situation, but they remove the infectious virus from the plasma from what we can see with function.   Cindy St. Hilaire:         Got it. So they're helping the cleanup process and in that cleaning up is where the virus within them activates. That is a really complicated mechanism.    Milka Koupenova:       Oh, they're sensing it in some form to alert the environment. It's hard to say how similar and how different they are unless you study them hint by hint next to each other. All I can tell is that particularly with SARS-C, you definitely see a lot more various kinds of extracellular vesicles coming out of them that you don't see the same way or rather through the same proportion with influenza. But what that means in how platelet activates the immune system with one versus the other, and that goes back to the prothrombotic mechanisms. That is exactly what needs to be studied and that was the call for this COVID compendium is to point out how much we have done as a team. As scientists who put heads together, as Mina said, superfast response, it's an amazing going back and looking at what happened to think of what we achieved. There is so much more, so much more that we do not understand how one contributes to all of these profound responses in the organs themselves, such as myocarditis. We see it's important and that will be the problem that we're dealing from here on trying to figure it out and then long COVID, right?   Cindy St. Hilaire:         Yeah. Related to what you just said about the mechanism, this cleanup by the platelets or the act of cleaning up helps trigger their activation, is that partly why the antiplatelet and anticoagulant therapies failed in patients? Can you speculate on that? I know the jury's still out and there's a lot of work to be done, but is that part of why those therapies weren't beneficial?   Milka Koupenova:       The answer to that in my personally biased opinion is yes. Clearly, the antiplatelet therapies couldn't really control the classical activation of a platelet. So what I think we need to do from here on is to look at things that we don't understand that non-classically contribute to the thrombotic response downstream. If we manage to control the immune response in some way or the inflammation of the infection or how a platelet responds to a virus, then perhaps we can ameliorate a little bit of the downstream prothrombotic effect. So it's a lot more for us to trickle down and to understand in my personal opinion.   DeLisa Fairweather:    There is one thing that was really remarkable to me in hearing your experience, Milka, is that I had developed an autoimmune viral model of myocarditis in mice during my postdoc. So I've been studying that for the last 20 years. What is unique about that model is rather than using an adjuvant, we use a mild viral infection so it doesn't take very much virus at all going to the heart to induce it. I also, more recently, started studying extracellular vesicles really as a therapy, and in doing that, inadvertently found out that actually, the model that I'd created where we passage the virus through the heart to induce this autoimmune model, we were actually injecting extracellular vesicles into the mice and that's what was really driving the disease. This is really brought out. So from early days, I did my postdoc with Dr Noel Rose. If you've heard of him, he came up with the idea of autoimmune disease in the '50s. We had always, in that environment, really believed that viruses were triggering autoimmune disease and yet it took COVID before we could really prove that because no one could identify them. Here we have an example and I think the incidence rates with COVID were so high for myocarditis because for the first time, we had distinguished symptoms of patients going to the doctor right at the beginning of their infection having an actual test to examine the virus, knowing whether it's present or not, whether PCR or antibody test, and then being able to see when myocarditis happened.   Cindy St. Hilaire:         Yeah. I think one thing we can all appreciate now is just some of the basic biology we've learned on the backend of this. Actually, those last comments really led well to the article that your team led, Dr Chung, about what we call long COVID, which I guess I didn't realize has an actual name, post-acute sequelae of SARS-CoV-2 or PASC is the now more formal name for long COVID. But what is it? We hinted at it that there's these bits about autoimmune and things like that. What counts as long COVID?   Mina Chung:   Yeah. Our article was led by Tamanna Singh. She did a fantastic job of putting this together. We've had, and others, theorized that the huge palette of symptoms that you can experience post-COVID, they can affect all these organ systems with brain fog, these atypical chest pains, postural orthostatic tachycardia, a lot of palpitations, atrial fibrillation, many weakness and fatigue. To us, really, you can get GI symptoms. We've been very interested in, is this an autoimmune phenomenon directed against nerves and all those things. It's also very interesting because many of the non-COVID syndromes that existed pre-COVID like POTS and chronic fatigue syndrome and a lot of other syndromes are associated with autoantibodies. So that is a very interesting area to explore. Is there a persistence of viral fragments. Is there autoimmunity? Is it also a component of persistence of the damage from the initial infection? So it's an area that still needs a lot of work and a lot of work is going into it, but this is like a post or inter pandemic of itself, so hopefully we'll get more insights into that.   Cindy St. Hilaire:         Yeah, it's really interesting. I have a friend who has very debilitating long COVID and one of her doctors had said, "If I didn't know any better, I would just describe this as a autoimmune type X." What do we know, I guess, about the current hypothesis of the pathogenesis of PASC? Are there any prevailing theories right now as to why it's occurring? Is the virus still active or is it these domino effects that are leading to multi-organ collapse of some sort?   Mina Chung:   Yeah. In some people, persistent viral particles can be identified for months, but whether or not that's what's triggering it, it's hard to know. We see more autoimmune disease that's been reported and various antibodies being reported. So those are clearly processes to be investigated. The microthrombosis is still up there in terms of potentially playing a role in long COVID.   Milka Koupenova:       Mina, you probably know better because you see patients, but to all I have been exposed to, long COVID does not really have a homogeneous symptom presentation and then a few theories as to what may be going on in these patients. Not everybody has a microthrombosis. Not everybody have a D-dimer elevated, but some people do. Some people have, as you pointed out, these spectacularly profound brain fog. People can't function. It's probably your friend, Cindy, right?   Cindy St. Hilaire:         Yeah.   Milka Koupenova:       So one of the theories that I have been, from a viral perspective, very interested in is that a lot of the symptoms in certain individuals such as fatigue, brain fog, sensitivity to light and skin can very well be explained by a flare-up of Epstein-Barr virus that may be what SARS-CoV-2 somehow is inducing. I don't know, DeLisa, what your experience with long COVID is as a scientist. I hope only. But I would like to hear your perspective too because it's so heterogeneous and it is amazing what happens.   DeLisa Fairweather:    I have a very interesting perspective from a number of different directions. One, as I mentioned before, my long history with Dr Rose and I've written many articles theorizing how viruses could cause autoimmune disease. This has grown and really, I think this has been extremely revealing during COVID for many of those theories. One thing that I write about in the review for this article is that mast cells, from all the research I've done with myocarditis in our model, mast cells are central to what is driving everything. We show they're the first innate immune cell acting as an antigen-presenting cell, completely driving the response in a susceptible pattern. One of the things that's very important in autoimmune disease is both sex and race. I'd say one of the big weaknesses we have in myocarditis pre-COVID and post-COVID has been ignoring what's going on with race. In the United States, myocarditis is 90%, 95% white men that are under 50 years of age and most of the cases are under 40 or some of the ones really associated with sudden cardiac death are under 30. So it's very specific. I've been studying sex and race differences and we see those exact differences in our animal models. In animal models, whether you're susceptible or not depends on how many mast cells you have. Well, I've proposed from the beginning, looking, I've written a lot of different sex difference reviews looking at viruses and autoimmune disease with different autoimmune diseases and hypothesizing and really seeing that mast cells do a lot of the things we're talking about. They have all of the receptors, the whole group of them that have been related to SARS-CoV-2 so they can be activated or stimulated by the virus itself. They act as a antigen-presenting cell. They're critical in the complement pathway as well as macrophages. We see the dominant immune phenotype really being macrophages. Mast cells just are usually not counted anywhere. And of course, these receptors, a lot of them have to do with enzymes and things that are all related to mast cells pathways. Then how they activate the immune response and lead it towards the pathway that leads to chronic autoimmune disease with increased autoantibodies in females, mast cells are very different by sex. This has to do also when we talked in the Review about myocarditis and pericarditis. It's both those appearing. Although clinically, we have really boxed them as separate things, because there is some definite clinical pericarditis phenotypes that are different, myocarditis in animal models is always myopericarditis. It always then, in that outer pericardial areas where mast cells sit, they sit around the vascular area in most concentrated. So when they degranulate, we see inflammation coming in the vessel, but really concentrated with fibrosis there and along the pericardium. So that's very typical of what's going on. When we shift anything that shifts that, it changes whether you have more pericarditis or less pericarditis and the vascular inflammation by altering anything that affects the mast cells. I talk a little bit about in the review, I think there's only been a few recent things looking at it in COVID, but I think mast cells and certain susceptibility to autoimmune diseases that occur more often in women can really predispose.We need to pay more attention to mast cells and what they might indicate for all these pathways.   Milka Koupenova:       I think we should study the platelet mast cell access at this point.   DeLisa Fairweather:    Yes.   Milka Koupenova:       Because as you're talking about these sex differences, which is spectacular, these things to me are so mind-boggling how one, the infection itself would be more prevalent in men, but then long COVID is more prevalent in women. All of these things and why we understand so very little, what we found about a few years ago in the Framingham Heart Study in the platelets from those people is that all toll-like receptors are expressed at the higher level in women and they associate with different things between men and female. For instance, toll-like receptors in women will associate more with a prothrombotic response while in male with pro-inflammatory response. I think they grossly underestimate the amount of our sex differences from cell to cell.   DeLisa Fairweather:    It is, yeah.   Mina Chung:   One other thing that I learned about the sex differences from this compendium is Mark Chappell also notes, you mentioned TLR and TLR7 and ACE2 are X chromosome in an area that he says escapes X-linked inactivation. So it could very well be involved in further.   DeLisa Fairweather: Further, yeah. And ACE2 is expressed more highly in male cells for what's been researched because of the sex difference in COVID, both the COVID infection   Cindy St. Hilaire:         So a variety of organ systems are impacted in patients with PASC, also referred to as long COVID, the lungs, the heart, the pancreas, the GI system, pretty much any system, the brain, nervous system. We've just been talking about the mast cell impact. I was really thinking in my head, well, the one thing that connects all of it is the vasculature. I'm a vascular biologist, so I have certain biases, I'm sure, but how much of the sequelae that we see is a function of vascular phenotypes?       Milka Koupenova:       I do think the vasculature is super important. It's clear that not all endothelial cells, for instance, will pick up the virus and respond to it. That's why you have this patchy breakage when you look at autopsies. Hence, platelets will respond according to what's local. That's why you find these micro thrombotic events at certain places. Why does it happen in each organ? How does the virus get to each organ to respond? Or is it just inflammation, but why is it in specific places? That's what we don't understand. That's where we need to go. Perhaps, as DeLisa points out, perhaps it's a lot more complicated than how we traditionally think of thrombosis. Actually, my personal bias, again 100% sure that it is a lot more complicated than the traditional mechanisms that we have understood, and that's where the immune system comes and autoimmunity perhaps stems from and they probably speak to each other, right? It's not just one thing.   DeLisa Fairweather:    Yeah. I think really, EVs are bringing lots of understanding. A lot of things we used to just think were maybe free-floating and the serum are inside EVs. I think that the immune response is perhaps even more specific than we ever thought and more regulated than we ever understood.   When an EV comes through a cardiomyocyte, whether it's from the mitochondria or through a lysosome, is part of what goes into its outer membrane, something that tells the immune system that that came from the heart, so it knows to go. This will solve a lot of our questions with autoimmune disease if it's very specific like that. It doesn't just have to be the release of free-floating cardiac myosin. We know cardiac myosin is the driver of the autoimmune response in myocarditis, but they're probably  much more fine-tuned.   Cindy St. Hilaire:         Yeah. I just would love to end with hearing from each of you. You each have your own domain of specialty. If I gave you a massive pot of money, what would be the question you would want to tackle? What's the gap you would love to answer?   Milka Koupenova:       We still don't understand specifically what kind of vesicles are coming out, what are their contents in addition to those vesicles. We don't understand. When it comes to platelets, what comes from their granules? We see these breakages of the membrane. Those are non-granule proteins, and non-granule proteins, they serve as dangerous associated molecular pattern signals and can be profoundly inflammatory to the surrounding environment, can be procoagulant. What are those? How are they affecting the surrounding environment? Ultimately, why is there a microthrombi? Why is there not a profound thrombosis everywhere? Thank goodness there isn't, but why isn't? That's what I would do with my money.   DeLisa Fairweather:    I think I would do something very similar. All of our research in our animal model, on the one side, we are looking in this viral myocarditis animal model and finding the EVs that come from that are driving myocarditis. On the other hand, we're using EVs that come from healthy human plasma or fat, and we're seeing a profound downregulation of everything if you give it early and we're trying to see how late you can give it and still get an effect. So looking at those and really understanding the components in the context of COVID and COVID vaccines to understand those components, I really think that's the future of where we're going to find what's causing disease and also how we can find therapies. They may be able to reverse this.   Mina Chung:   Yeah, I'm interested very much in the autoimmunity and the autoantibodies that are    and how they may react with those microthrombi. Perhaps there's autoantibodies within a lot of that material. We're looking at using human and pluripotent stem cell-derived cell models to study the effects of those. That is what I would use our money for.   Cindy St. Hilaire:        Well, Dr Mina Chung, Dr DeLisa Fairweather, Dr Milka Koupenova, thank you all so much for joining me today and talking about not only the articles that you wrote and with your colleagues, but also other articles in this amazing compendium. I do think this is one of the first all-encompassing compendiums or group of articles that focus specifically on COVID and cardiovascular disease. So thank you all so much.   Mina Chung:   Thank you.   DeLisa Fairweather:    Thank you.   Milka Koupenova:       You're welcome.   Cindy St. Hilaire:         That's it for highlights from the April 28th and May 12th issues of Circulation Research. Thank you for listening. Please check out the CircRes Facebook page and follow us on Twitter and Instagram with the handle @circres and #DiscoverCircRes. Thank you to our guests, Dr Mina Chung, Dr DeLisa Fairweather and Dr Milka Koupenova. This podcast is produced by Ishara Ratnayaka, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy text for the highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, your on-the-go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2023. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, visit ahajournals.org.    

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.06.531305v1?rss=1 Authors: Bregy, I., Radecke, J., Noga, A., van den Hoek, H., Kern, M., Haenni, B., Engel, B. D., Siebert, C. A., Ishikawa, T., Zuber, B., Ochsenreiter, T. Abstract: In contrast to many eukaryotic organisms, trypanosomes only contain a single mitochondrion per cell. Within that singular mitochondrion, the protist carries a single mitochondrial genome that consists of a complex DNA network, the kinetoplast DNA (kDNA). Segregation of the replicated kDNA is coordinated by the basal body of the cell's single flagellum. The tripartite attachment complex (TAC) forms a physical connection between the proximal end of the basal body and the kDNA. This allows anchoring of the kDNA throughout the cell cycle and couples kDNA segregation with the separation of the basal bodies prior to cell division. Over the past years, several components of the TAC have been identified. To shed light on the structure of the cytoplasmic part of the TAC (known as the exclusion zone), we performed cryo-electron tomography on whole cells. This allowed us to acquire three-dimensional high-resolution images of the exclusion zone in situ. We observed that the exclusion zone filaments offer great mechanical flexibility for basal body movement. We measured the dimensions of the individual structural elements of the area, as well as the overall orientation and positioning of the basal bodies towards the mitochondrial kDNA pocket. Using a combination of experimental data and modelling, we generated a structural model of the exclusion zone protein p197. Our findings suggest that the majority of p197 consists of a string of spectrin-like repeats. We propose that these structural units provide the architecture of a molecular spring and that they are required in the TAC to withstand the mechanical forces generated through basal body repositioning events during kDNA segregation and motility of the organism. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.27.530371v1?rss=1 Authors: Candray, K., Nakagama, Y., Masamichi, I., Nakagama, S., Tshibangu-Kabamba, E., Takeda, N., Sugiura, Y., Nitahara, Y., Michimuko-Nagahara, Y., Kaku, N., Onizuka, Y., Arias, C.-E., Mejia, M., Alas, K., Pena, S., Maejima, Y., Komuro, I., Nakajima-Shimada, J., Kido, Y. Abstract: Chagas disease can lead to life-threatening cardiac manifestations that occur more frequently in geographic areas more prevalent with the TcI/II circulating genetic strains. To elucidate the differential transcriptomic signatures of the cardiomyocyte resulting from infection with TcI/II or TcVI T. cruzi strains and explore their relationships with pathogenesis, HL-1 rodent cardiomyocytes were infected with TcI/II or TcVI T. cruzi trypomastigotes. RNA was isolated serially post-infection for microarray analysis. Enrichment analyses of differentially expressed genes (fold-change greater than or equal to 2 or less than or equal to 0.5) highlighted the over-represented biological pathways. We found that Oxidative stress-related GO terms, 'Hypertrophy model', 'Apoptosis', and 'MAPK signaling' pathways (all with p less than 0.01) were upregulated. 'Glutathione and one-carbon metabolism' pathway, and 'Cellular nitrogen compound metabolic process' GO term (all with p less than 0.001) were upregulated exclusively in the cardiomyocytes infected with the TcI/II strains. Upregulation in the oxidative stress-related and hypertrophic responses are shared hallmarks with viral myocarditis, another inflammatory cardiac pathology. Nitrogen metabolism upregulation and Glutathione metabolism imbalance may implicate the relation of nitrosative stress and poor oxygen radicals scavenging in the unique pathophysiology of chagasic cardiomyopathy development. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

A leishamniose é uma doença de grande importância na medicina veterinária e Saúde Pública, causada pelo protozoário do gênero Leishmania spp, é considerada uma zoonose, causando sofrimento não só para seres humanos, mas também para os cães. Para responder às dúvidas mais comuns sobre esse tema, convidamos o Prof. Dr. Arlei Marcii, graduado em Ciências Biológicas Modalidade Médica pela Universidade Bandeirante de São Paulo, atua na linha de pesquisa de Doenças Parasitárias, Infecciosas e Zoonoses com ênfase em parasitas do gênero Trypanosoma e Leishmania.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.22.521263v1?rss=1 Authors: Albisetti, A. C., Douglas, R. L., Welch, M. D. Abstract: Trypanosoma brucei, the causative agent of African sleeping sickness, uses its flagellum for movement, cell division, and signaling. The flagellum is anchored to the cell body membrane via the flagellar attachment zone (FAZ), a complex of proteins, filaments, and microtubules that spans two membranes with elements on both flagellum and cell body sides. How FAZ components are carried into place to form this complex is poorly understood. Here, we show that the trypanosome-specific kinesin KIN-E is required for building the FAZ in bloodstream-form parasites. KIN-E is localized along the flagellum with a concentration at its distal tip. Depletion of KIN-E by RNAi rapidly inhibits flagellum attachment and leads to cell death. A detailed analysis reveals that KIN-E depletion phenotypes include failure in cytokinesis completion, kinetoplast DNA mis-segregation, and transport vesicle accumulation. Together with previously published results in procyclic form parasites, these data suggest KIN-E plays a critical role in FAZ assembly in T. brucei. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

On episode #17 of the Infectious Disease Puscast, Daniel and Sara review the infectious disease literature for the previous two weeks, 11/24/22 – 12/8/22. Hosts: Daniel Griffin and Sara Dong Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of Puscast! Links for this episode Antiretroviral drugs for treatment and prevention of HIV infection in adults (JAMA) Outcomes of short versus long duration of antibiotic therapy for residual osteomyelitis in diabetic foot infection (Journal of Antimicrobial Chemotherapy) Rectal culture-based versus empirical antibiotic prophylaxis to prevent infectious complications in men undergoing transrectal prostate biopsy (CID) Outbreak of Burkholderia stabilis infections associated with contaminated nonsterile multiuse ultrasound gel (CDC) Factors associated with receiving longer than recommended therapy among culture-negative pulmonary tuberculosis patients (OFID) Seasonality of healthcare-associated Stenotrophomonas maltophilia (ASHE) Rezafungin versus caspofungin for treatment of candidaemia and invasive candidiasis (The Lancet) Characteristics of antifungal utilization for hospitalized children in the United States (ASHE) Cutaneous blastomycosis presenting as a nonhealing wound (NIH) Evaluation of the diagnostic accuracy and clinical utility of fungla profile (OFID) Parasitic infection increases risk-taking in a social, intermediate host carnivore (Nature) Efficacy and safety of acoziborole in patients with human African trypanosomiasis caused by Trypanosoma brucei gambiense (The Lancet) Simple nodular cutaneous Leishmaniasis caused by Autochthonous Leishmania orientalis (AJTMH) Emerging and Reemerging Infectious Diseases (NEJM) Music is by Ronald Jenkees

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.23.517661v1?rss=1 Authors: Won, M. M., Krüger, T., Engstler, M., Burleigh, B. A. Abstract: Throughout its complex life cycle, the uniflagellate parasitic protist, Trypanosoma cruzi, adapts to different host environments by transitioning between elongated motile extracellular forms and non-motile intracellular amastigote forms that replicate in the cytoplasm of mammalian host cells. Despite their name, intracellular T. cruzi amastigotes retain a short flagellum that extends beyond the opening of the flagellar pocket with access to the extracellular milieu. Contrary to the long-held view that the T. cruzi amastigote flagellum is inert, we now report that this organelle is motile and displays quasiperiodic beating inside mammalian host cells. Kymograph analysis determined an average flagellar beat frequency of ~0.7 Hz for intracellular amastigotes. Similar beat frequencies were measured in extracellular amastigotes following their isolation from host cells. Inhibitor studies reveal roles for parasite mitochondrial respiration and intracellular calcium availability in modulating flagellar beat in T. cruzi amastigotes. Together, these findings demonstrate that flagellar motility is an intrinsic property of T. cruzi amastigotes and suggest that this organelle may play an active role in the parasite infection process. To our knowledge, this is the first record of an intracellular eukaryotic flagellum beating within another eukaryotic cell. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

On episode #15 of the Infectious Disease Puscast, Daniel and Sara review the infectious disease literature for the previous two weeks, 10/27/22 – 9/9/22. Hosts: Daniel Griffin and Sara Dong Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of Puscast! Links for this episode Clinical presentation and severity of adenovirus detection alone vs adenovirus co-detection with other respiratory viruses in US children (JPID) Effectiveness of different antimicrobial strategies for staphylococcal prosthetic joint infection (OFID) Clinical impact of ceftriaxone resistance in E. coli bloodstream infections (OFID)  Adjunctive Gentamicin and Rifampin in staphylococcal prosthetic valve Endocarditis (OFID) Diagnostic performance of physician gestalt for bacteremia in patients in the process of being admitted with suspected infection (OFID) Effectiveness of quinolone prophylaxis in pediatric acute leukemia and hematopoietic stem cell transplantation (OFID) Risk factors for Vancomycin drug reaction with Eosinophilia and Systemic symptoms syndrome (JAMA) Prospective evaluation of the fungitell 1>3 beta-d-glucan assay as a diagnostic tool for invasive fungal disease (Wiley) Safety and efficacy of a monoclonal antibody against malaria in Mali (NEJM) Hospitalizations associated with strongyloidiasis in the United States (CID)  Prophylactic benznidazole treatment fails to prevent Trypanosoma cruzi infection in dogs (PLOS NTD) Baker's dozen of top antimicrobial stewardship intervention publications for hospitalized patients (OFID) Baker's dozen of top antimicrobial stewardship intervention publications in non-hospital care settings in 2021 (OFID) Medical student debt and the US ID workforce (CID) Music is by Ronald Jenkees

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.11.516029v1?rss=1 Authors: Shimogawa, M. M., Wijono, A. S., Wang, H., Sha, J., Szombathy, N., Vadakkan, S., Pelayo, P., Jonnalagadda, K., Wohlschlegel, J. A., Zhou, Z. H., Hill, K. Abstract: Eukaryotic motile cilia/flagella are conserved organelles important for cell propulsion and fluid flow, typically built around a "9+2" axoneme of nine doublet microtubules (DMTs) encircling a central pair of singlet microtubules. The DMT lumen is lined with an interconnected network of microtubule inner proteins (MIPs), some conserved and others lineage-specific. MIPs augment the tubulin lattice of the DMT, directly impacting stability, fine structure, and motility, thus providing an important source of lineage-specific adaptations. Trypanosoma brucei is a flagellated eukaryotic pathogen with distinctive motility that is critical for pathogen transmission and pathogenesis. Prior studies revealed lineage-specific T. brucei MIPs, but their identities are unknown. To identify T. brucei MIPs, we examined flagellum structure and composition following knockdown of FAP106, a conserved MIP at the inner junction (IJ) connecting A- and B-microtubules of the DMT. FAP106 knockdown resulted in short flagella and defective parasite motility, supporting a role for MIPs in T. brucei flagellum stability and motility. Cryogenic electron tomography (cryoET) and quantitative proteomics identified several conserved MIPs and lineage-specific MIP structures and MIP candidate proteins (MCs) that depend on FAP106 for stable assembly. We further demonstrate by knockdown and fitting AlphaFold models to cryoET maps that one of these, MC8, is a newly identified lineage-specific MIP required for normal parasite motility. This work provides an important advance toward elucidating the order of assembly of MIPs at the cilium inner junction and identifies trypanosome proteins specific to these deadly pathogens that represent targets to consider for therapeutic intervention. SIGNIFICANCE STATEMENTMotility characteristics of cilia/flagella differ dramatically between species to accommodate organism-specific motility needs. Recently discovered microtubule inner proteins (MIPs) inside microtubules are thought to contribute to species-specific motility characteristics but are largely uncharacterized. The flagellated parasite, Trypanosoma brucei, exhibits many unique motility features considered important for moving through host tissues to cause disease, but identities of parasite-specific MIPs are unknown. Here, we combine structural biology, mutant analysis, and quantitative proteomics to identify lineage-specific MIPs in T. brucei. We demonstrate that the conserved MIP, FAP106, is required for motility and stable assembly of several other MIPs, including trypanosome-specific MIPs required for motility. Our studies advance fundamental understanding of MIP assembly mechanisms, while identifying parasite-specific proteins as potential targets for therapeutic intervention. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

¿Usted ha escuchado hablar del mal de Chagas? ¿Sabía que es una enfermedad olvidada y desatendida? Aunque afecta a entre unas 6 y 7 millones de personas en el mundo, tiene esta connotación porque lo hace principalmente en poblaciones de bajos recursos y con un acceso limitado a servicios de salud. El parásito que la produce, el Trypanosoma cruzi (tripa no se asoma en la cruz), puede pasar años e incluso décadas antes de manifestarse en síntomas que, en el peor de los casos, afectan el corazón y otros órganos. Este es un contenido patrocinado por la Iniciativa Medicamentos para Enfermedades Olvidadas (DNDi por sus siglas en inglés), una organización que trabaja en la investigación y el desarrollo de medicamentos para atender a este tipo de enfermedades. Si le gusta lo que hacemos, considere compartir nuestro contenido y apoyarnos en patreon.com/shotsdeciencia

This monster is somewhat missed named. The only kissing it does is biting you near your mouth and pooping on your face at night. The kissing bug also spreads a deadly parasitic disease prevalent in south and central America. The microbes, named "Trypanosoma cruzi" crawl in through the bite wound left by the kissing bug, or through your mouth when you scratch and spread the feces. Kissing bugs are gross and dangerous because the parasite they carry causes "Chagas disease" which can scar your heart tissue. Chagas disease can go unnoticed for years... Do you have kissing bugs in your walls? Today we learn 5 Gross Kissing Bug Facts. This is a "Square YouTube Short". Subscribe to Animal Science TV for full-screen, full-length videos all about animals! https://www.youtube.com/AnimalScienceTV https://www.patreon.com/AnimalScienceTV https://www.AnimalScienceTV.com https://www.facebook.com/AnimalScienceTV https://twitter.com/AnimalScienceTV Special thanks to my current Patreons: Lab Assistants: The Borbs Research Associates: Susie, Julie Acepilot, GotMountains Lead Scientists: Lisa, Alex, Emily, Sarah, Bianco Artistica, Epsilon is Greater Than #shorts #kissingbug #kissingbugs Specific Credits: https://animalsciencetv.com/credits-and-attributions-2022/

Chagas disease is also known as “American Trypanosomiasis.” It's caused by a blood parasite called Trypanosoma cruzi, which is transmitted by kissing bugs. Chagas disease affects people as well as dogs and other animals. On today's show, we are going to focus on Chagas in dogs. Joining me today to discuss this topic is Carlos Rodriguez, Carlos is the serology section head at the Texas A&M Veterinary Medical Diagnostic Lab.

88: Pt. 2 Solutions for Shedding from the Quantum Realm - Kurt Johnson & Taser Wraye on Spirit Centered Business Bralynn, Kurt & Taser continue the discussion from Pt. 1. In case you missed it, visit SpiritCenteredBusiness.com/podcast to catch up. TOPICS:- It's all about the blood- How graphene oxide affects the body- Symptoms of graphene oxide poisoning- Biome Upgrade (Bi-Up) reverses negative responses in the body- How Bi-Up deconstructs the self-replication process- Communicating with fungus- Hydras and how they affect the cells- God downloaded the way to give new direction to spike proteins- Hydras are formulated in labs and given job descriptions- Symptoms from the injection ingredients- The Bi-Up products and directions- The good news: going back to our original design GOLDEN NUGGETS:1) Hemoglobin in healthy red blood cells that are round and carry a negative charge on the outside of the membrane. Normally each cell flows through the vascular system with no problem. When graphene oxide is introduced to the body via the injection, it gets into the red blood cells and they lose their negative charge and become positivly charged. This causes the red blood cells to clump and to clot which causes a problem with the flow of the blood.2) Graphene oxide produces tubules in the blood and begins to replicate itself. As it gets bigger they can't get through the capillary system where the blood flows from the arteries to the veins and back to the heart. This becomes life threatening.3) For the body's protection the hemoglobin tries to intake as much graphene oxide in the blood as it can to protect and maintain life. 4) A few symptoms from the effects of the injection are: Blood clots in the brain and in the heart, shortness of breath, feeling tired, rashes, headaches, and irregular menstrual cycles.5) There are parasites formulated in a lab, such as Trypanosoma, in the implant as well. This one's job is to grow and replicate itself like the spike proteins do. The parasite's food source is protein. Part of the download Taser received from God gave him the way to reverse the directives and change the assignment of the parasites so the immune system can locate the invaders and the parasites would now eat the spike protein instead. This means no more replication in the cell, so no more clotting and it can now exit the body. 6) Hydra Linnaeus is a parasite created in the lab and it is designed to make changes in the DNA. They are double celled organisms that grow large enough to be seen with the naked eye.. They multiply rapidly in the body when they come into contact with graphene oxide. 7) Spike proteins stop the body's natural and normal DNA repair. (It was proven on October 13, 2021 that spike protein causes DNA damage.) Normal spike protein has a connection site on the membrane of the cell to release certain information into the cell and then it gets replicated and the spike falls off. They have engineered the implant to cause the spike to remain and lock into the membrane and continue its activity. The ridges the spike has can slice the red blood cells that are going by and the cell will then leak its contents and this causes more damage. This is why it was so important and amazing that God gave the directive to be able to reverse this assignment and get the parasite to eat these spike proteins and remove them from the body. 8) Fungus plays a key role in the functionality of the Biome Upgrade product because fungus is one of the oldest living organisms on the planet, and it's job is to break down and deconstruct things, while being extremely adaptive to its environment. Biome Upgrade (Bi-Up) Product:Bi-Up is designed to upgrade your immune system so it can be alerted to invaders in the bio-weapon that have been designed to slip past the immune system undetected and destroy organs, such as reproductive organs and the heart. There are two Bi-Up products, one for those susceptible to shedding, and one for those who have been implanted and now want to heal themselves and stop being a weapon to others. Each has 2 components: One is the dermal spray you use on your neck and upper chest area where the thymus gland is located. The other one is to be used orally. Simply pump it into your mouth and swish it around for a minute before swallowing, which allows it to get into your system quickly. The two products used together are like a double punch to the Biome. For those warding off shedding, use this for 3 months. And for those already implanted, use for 6 months. Both are used 5 days on and two off. The two days off we recommend if possible to fast so the body can have a break as it is removing the excess toxins from the body. Use your discretion on how you choose to fast and how many times during the program. Bi-Up is formulated using many equations, directives, communicating through frequency and intention in the quantum realm along with working with the fungi in the body. Because frequency and intention are critical to the efficacy of the product, there is a 30-minute “Activation” video that you may use as well. QUOTES:- Leviticus 17:11 “For the life of the flesh is in the blood”…- God always allows a way to turn around the bad for the good if we are open.- We blow the shofar frequency over all of our products. We feel like it releases the frequency of God's breath into our products. RESEARCH: NOTE from Bralynn: I strongly urge you to do your own research. Look at the source of funding for the research - who is behind it. Follow the money. Don't take anything at face value. Dig. Pray about it, use common sense, and always pay attention to a check in your spirit about any info you hear. I haven't vetted every source listed. These may provide a starting point for your own study, and for drawing your own conclusions.Dr. Brian Bridle the Viral Immunologist and Associate Professor at the University of Guelph speaks out: (32-min long version) https://www.facebook.com/watch/?extid=CL-UNK-UNK-UNK-IOS_GK0T-GK1C&v=4476495142430002Graphene oxide found in injected and non-injected patients: https://www.heartpublications.co.uk Dr. Ariyana Love hydras, mRNA, and gene therapy: https://tokentube.net/v/2167616390/-81---Dr--Ariyana-love- Dr. Daniel Negase helping people to open their eyes: https://www.bitchute.com/video/VAm0QaweaN4vDr. Ariyana Love: What is in the jab: https://www.redvoicemedia.com/2021Dr Zelenko explains the bioweapon: https://rumble.com/vogp3p-dr.-zelenkoDr. Ariyana Love: Hydras and Parasites: https://www.redvoicemedia.com/2021/10/doctorIs Covid 19 a bio-weapon: Dr Richard Fleming: https://thehighwire.com/videos/is-covid-19-a-bio-weaponMom blames Pfizer vaccine on her 16 year old son's death: https://www.redvoicemedia.com/2021/10/healthy-16-year-old-boy Dr Zelenko, protect the kids: https://www.redvoicemedia.com/2021/10/dr-zelenko-drops-atomic-bomb-where-did-the-influenza-go/Dr. John Cambell speaks to a vax-injured mountain bike racer: https://www.redvoicemedia.com/video/2021/10/covid-vaccine-injury Dangerous spike proteins: and the complications: https://www.redvoicemedia.com/video/2021/10/spiked- Dr. Peter McCullough, exposing the corruption on medical tyranny: https://www.redvoicemedia.com/video/2021/11/dr-peter-mccullough-issues-emergency-warning-vaccine-created-spike-protein Dr. Bryam Bridle, censorship and smear campaigns on Doctors and Scientists: https://www.bitchute.com/video/gNT9nW6mmkVO Dr. Zelenko: Jabs are premeditated murder: https://www.redvoicemedia.com/video/2021/11/video-covid-jabs-are-premeditated Hydra Linnaeus found in the vaccine: NOTE from Bralynn: The info is interesting, but the guy speaking is not identified, so that always makes me question it. Just a heads up. https://www.bitchute.com/video/PrWRZOeQMBzF/?list Professor Sucharit Bhakdi, proof that puts an end to Sars-CoV-2 narrative: https://odysee.com/@OracleFilms:1/Dr.-Sucharit-Bhakdi-Oracle-Films-Message-HD:1?r=EPrs4aBK5AuJKJCNxG9kGHS96ytPAvbbLINKS:- Get all 3 parts of this series, and become a member to buy the Biome Upgrade solution: http://SpiritCenteredBusiness.com/spray - Join the Ekklesia for Business: SCB Activation Group- Spirit realm Activations for your Business: https://spiritcenteredbusiness.com/coaching- Join the SCB Tribe: http://facebook.com/groups/scbtribe- Design your Leveraged, Scalable & Sustainable business model from Heaven's blueprint and bring the Transformation in the world you and your business were destined to create. Schedule a FREE Discovery call with Bralynn: http://Bralynn.appointlet.com/s/discovery

El calentamiento del planeta y las fuertes sequías están provocando que en regiones cercanas a los polos se estén registrando enfermedades que son más propicias de las regiones tropicales. En el mundo hay entre 6 y 7 millones de personas infectadas por el Trypanosoma cruzi, el parásito causante de la enfermedad de Chagas, la mayoría de ellas en América Latina. Hablamos de ello con el doctor Juan Diego Maya, director del Instituto de Ciencias Biomédicas de la Universidad de Medicina de la Universidad de Chile, que dirige también una investigación y un ensayo clínico para atajar el Mal de Chagas, de difícil curación. Escuchar audio

Please join author Maria Nunes and Associate Editor Ntobeko Ntusi as they discuss the article “Incidence and Predictors of Progression to Chaga Cardiomyopathy: Long-Term Follow-Up of Trypanosoma cruzi-Seropositive Individuals.” Dr. Carolyn Lam:             Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley:           And I'm Dr. Greg Hundley, Associate Editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Well Carolyn, this feature this week, we're going to talk about Chagas disease and we have some really important long-term, really for the first time, observational data and a cohort that's been followed in Brazil. And it's just a wonderful discussion from a team that's been working very hard in this area over an extended period of time. But before we get to that, how about we grab a cup of coffee and get started on some of the other articles in this issue? Would you like to go first? Dr. Carolyn Lam:             I would. And with your coffee, I would like to tell you about non-combustible nicotine or tobacco products. Fancy a smoke with your coffee? Well, you know that those are novel forms of nicotine consumption composed of things like nicotine vaping products that vaporize the nicotine-containing fluids and heated tobacco products that really heat the tobacco products without combustion. Now, these have recently gained popularity because they're portrayed as being safer modes of smoking compared with the traditional combustible cigarettes. However, their associations with subsequent cardiovascular disease risks are still unclear. So Greg, here's today's quiz. Gosh, I miss our quizzes. What do you think? Are they safer or are they not? Dr. Greg Hundley:           Oh, Carolyn, you're catching me on this and I never know which way to go, but I'm going to guess not. How about you tell us? Dr. Carolyn Lam:             Well, the paper will tell us, and this is from co-corresponding authors Dr. Lee from Seoul National University Bundang Hospital and Dr. Park from Seoul National University College of Medicine and their colleagues. And they basically studied more than 5,000,000 adult men who underwent health screening examinations during both a first and second phase of health screening periods from the Korean National Health Insurance Service Database spanning 2014 to 2018. Initial combustible cigarette smokers who subsequently quit that cigarette smoking and converted to a non-combustible nicotine or tobacco product use was associated with a lower incident cardiovascular disease risk compared to those who continue the combustible cigarette use. However, compared with combustible cigarette quitting without using these non-combustible substitutes, those who ceased smoking but continued with the non-combustible products was associated with a higher cardiovascular disease risk. So the take home message is although the non-combustible nicotine or tobacco products may be associated with a lower cardiovascular disease risk compared with continued combustible cigarette smoking, those who quit without using these substitutes may benefit the most in reducing the risk of developing future cardiovascular disease events. And this is discussed in a wonderful editorial by Dr. Auer, Diethelm and Berthet. Dr. Greg Hundley:           Very nice, Carolyn. Great presentation and really new information in this space. Well, my paper comes from the world of preclinical science and it involves long noncoding RNAs. And Carolyn, they are important regulators of biological processes involved in vascular tissue homeostasis and cardiovascular disease development. And so, the current study, led by Professor Lars Maegdefessel from Karolinska Institute, assessed the functional contribution of the long noncoding RNAs myocardial infarction associated transcripts and their relationship to atherosclerosis and carotid artery disease. Dr. Carolyn Lam:             Hmm, interesting. They are the rage, these lncRNAs. So what did they find, Greg? Dr. Greg Hundley:           Right, Carolyn. So long noncoding RNAs possess key regulatory functions directly interacting and mediating expression and functionality of proteins, other RNAs, as well as DNA. Next, the long noncoding RNA myocardial infarction associated transcript plays a key role during atherosclerotic plaque development and lesion destabilization. Its expression becomes highly increased in high risk patients with vulnerable plaques. And so, Carolyn, the take home therapeutic targeting of the long noncoding RNA myocardial infarction associated transcript, using antisense oligonucleotides, well that offers novel treatment options for patients with advanced atherosclerosis in the carotid arteries that are at risk of stroke. Dr. Carolyn Lam:             Oh, very interesting. So from the preclinical world back to the clinical world with an important clinical trial. Now, we know that percutaneous closure of the left atrial appendage is an alternative to chronic oral anticoagulation to reduce stroke risk in patients with nonvalvular atrial fibrillation. The Amplatzer Amulet Left Atrial Appendage Occluder IDE trial, called the Amulet IDE trial, was designed to evaluate the safety and effectiveness of the dual seal mechanism of the Amulet left atrial appendage occluder compared with the WATCHMAN device. And here, 1,878 patients with nonvalvular atrial fibrillation at increased risk of stroke were randomly assigned to undergo percutaneous implantation of a left atrial appendage occluder with the Amulet occluder or a WATCHMAN device. And the primary end points included safety, which was a composite of procedure-related complications all cause death or major bleeding at 12 months, and effectiveness, which was a composite of ischemic stroke or systemic embolism at 18 months. They also looked at the rate of left atrial appendage occlusion at 45 days. And this paper is from Dr. Lakkireddy and colleagues from Kansas City Heart Rhythm Institute. Dr. Greg Hundley:           Well Carolyn, these devices, they are really being heavily tested in patients with atrial fibrillation. So what did they find? Dr. Carolyn Lam:             The Amulet occluder was non-inferior with respect to safety and effectiveness compared to the WATCHMAN device, and superior with respect to left atrial appendage occlusion; however, procedure-related complications were higher with the Amulet occluder, largely related, perhaps, to more frequent pericardial effusion and device embolization. And the authors noted that the procedure-related complications decreased with operator experience; however, I think all of this still needs to be further investigated. Well, those were really nice original papers, but let's also discuss what else there is in today's issue. There is an exchange of letters between Drs. Mueller and Allen regarding the article “Diagnostic Performance of High Sensitivity Cardiac Troponin T Strategies and Clinical Variables in a Multisite U.S. Cohort.” There's a perspective piece by Dr. Olson, “Toward CRISPR Therapies for Cardiomyopathies.” Dr. Greg Hundley:           And Carolyn, I've got a research letter from Professor Layland entitled “Colchicine in Patients with Acute Coronary Syndromes: Two Year Follow Up of the Australian COPS Randomized Clinical Trial.” Well, what a great set of papers that we've discussed. Now, let's get on to that feature discussion and learn a little bit more about the longitudinal history and progression of cardiovascular disease and patients with Chagas disease. Dr. Carolyn Lam:             Yay. Let's go, Greg. Dr. Greg Hundley:           Well, listeners, we are here for our feature discussion today and a very exciting one we have, pertaining to Chagas disease. And we have with us today Dr. Maria Nunes from Belo Horizonte, Brazil, and also one of our Associate Editors, Dr. Ntobeko Ntusi from Cape Town, South Africa. Welcome to you both. And Maria, we'll start with you. Could you describe for us some of the background information pertaining to your study and what was the hypothesis that you wanted to address? Dr. Maria Nunes:             Yes, thank you for these opportunities. My main hypothesis is that Chagas disease is the major cause of dilated cardiomyopathy in endemic areas. So we selected patients without cardiomyopathy at baseline to see if the Trypanosoma cruzi seropositivity is a predictor of further developing of cardiomyopathy. Dr. Greg Hundley:           Very nice. And so tell us, how did you construct this study? What was your design? And then also, maybe describe for us how you selected the participants for this study. Dr. Maria Nunes:             We selected the participants from two blood donor centers. One in Sao Paulo and one in Montes Claros, which is north of Minas Gerais State. We select blood donors because it's the way that we have Chagas disease's screening tests. And in asymptomatic patients, usually at the hospital, patients comes to us with heart failure or a kind of symptoms related to Chagas disease. Our main goals in this study is to select healthy participants based on the screen test of Trypanosoma cruzi. So the population was blood donors selected from two centers. Dr. Greg Hundley:           Very good. And then again, your study design. So did you follow these two groups of individuals longitudinally over time, and for how long? Dr. Maria Nunes:             Yes, we have different visits of this study with the patients initially was selected at first in 1996 and 2002. At this time, they don't have cardiovascular exams. And our study actually is starting 2008 to 2010, and we select all these patients with all comprehensive cardiovascular evaluation with the clinical examination, echocardiogram and electrocardiogram, and then just the baseline for our patient population. And we follow them 10 years on average until 2018, 2019. Dr. Greg Hundley:           Very nice. So it sounded like from individuals in two regions of Brazil, identified those through screening of the blood, and I guess these were blood donors, and then performed a series of cardiovascular exams 2008 to 2010 and followed them for the next 10 years. And you're going to tell us about the results that occurred 2018 to 2019. And so what were those results? Dr. Maria Nunes:             We found that Trypanosoma cruzi seropositive is a risk factor for developing cardiomyopathy. Nowadays, this is still a risk factor, seropositive without cardiomyopathy at baseline has two times higher risk of developing cardiomyopathy compared to the seronegative controls. And we have also detected that the parasite load or the level of parasite in the blood expressed by antibodies against Trypanosoma cruzi is an important risk factor for disease progression. That means some patients have Chagas disease, but the level of antibodies is not too high. These patients go well. And other hand, the patients with high level antibodies means the parasite load may be higher too. This is the high risk of disease progression to cardiomyopathy or of dying too. Dr. Greg Hundley:           Very nice. And were there any subgroups of patients where you found these relationships to be particularly more striking? So for example, the elderly, or was there a discrepancy based on sex, men versus women? Dr. Maria Nunes:             Yes, other studies has already shown that the male gender is a risk factors in Chagas disease. Usually they progress more, they have more severe clinical presentation, usually die at the age between 30 and 50 years old, the most productive years of the life. That's why Chagas is so important here in Brazil and Argentina, in Latin America countries because people die at early ages. Dr. Greg Hundley:           And your results confirmed what was previously known in that regard. Dr. Maria Nunez:             Yes, patients with developing cardiomyopathy with heart failure has a high mortality rate. And then even patients with cardiomyopathy detected by exams like based on ECG or echo, they asymptomatic, but they progress more for dying or to develop cardiomyopathy compared to seronegative with similar risk effects for cardiovascular disease, such as hypertension, diabetes, smoking. Dr. Greg Hundley:           Very good. Well Ntobeko, you see many papers come across your desk as an Associate Editor for Circulation, and what attracted you to this paper and the results that Maria has described? Dr. Ntobeko Ntusi:          Thank you, Greg. I was attracted to this paper because it's an important natural history study of Chagas disease. But secondly, it's also one of the largest contemporaneous cohorts of Chagas disease which provides important insights and advances in our knowledge with regard to this clinical entity. And for me, there were three things that stood out. The first one was an important description of the outcomes of Chagas cardiomyopathy. The second was the contemporaneous description of the epidemiology in a well-characterized cohort. And the third and novel contribution was the description of the determinants of disease progression. So I thought overall, the really important contribution to the field. Dr. Greg Hundley:           Very good. And for those that might not live in the endemic area, but might occasionally encounter someone with Chagas disease, what results from this paper can we use to help manage patients in this situation? Dr. Ntobeko Ntusi:          Thanks, Greg. So this was a study which had a number of really positives. Firstly, it's a large study, it was non acute [inaudible 00:16:42] design and it used PCR for diagnosis. And unlike many other studies, also ascertained antibody levels and had very good clinical characterization, which included electrocardiographic, echocardiographic assessment, including serum assessment of proBNP and CK-MB. And all really important take home messages are for me. The first one is understanding that the relationship of your antibody levels and baseline LV function to mortality. In other words, are finding that in those with existing LV structural abnormalities, or higher levels of antibody titers, mortality was higher. The second important contribution is a description of the incidence of Trypanosoma cruzi, and this was highest as one would expect in the seropositive donors and much lower in seronegative donors. The third important contribution relates to our improved understanding of the determinants of disease progression, which were related to the Trypanosoma cruzi antibody levels. In other words, the higher your antibody titers, the quicker you progressed to manifest the cardiomyopathic phenotype. And then lastly, the predictors of mortality, which were related to your PCR being positive, as well as your antibody titers. Important is this contribution is there are a number of important caveats. The first is that the study is limited by the huge amount of loss to follow up, which as you can imagine, adds a number of biases to our conclusions. The second is that the observations may of course be confounded by comorbidity in particular because these patients are older and had higher comorbidity. The third is that we assume that the PCR positivity and antibody titers actually correlate with parasite pattern, but in fact, we know that is not always the case. And then lastly, for people who read this paper from non-endemic parts of the world, the result may not be clearly generalizable to those parts of the world. Dr. Greg Hundley:           Very nice. Well, we've had a great discussion, listeners. From Maria and Ntobeko sort of presenting the paper and then what are some of the take home messages. So now I'd like to go back to both of them and Maria, first you and then Ntobeko. Maria, what do you think is the next study to really be performed in this sphere of research? Dr. Maria Nunes:             We may should stratify patients with Chagas disease. Those who have high antibodies titers should refer to a kind of treatment or benznidazole treatment. We should intervene in this subgroup. Dr. Greg Hundley:           Very good. And Ntobeko, anything to add? Dr. Ntobeko Ntusi:          Yes, Greg, I think that there are two important next steps. The first one is that I think we need other large designed prospective studies that will validate the observations by Dr. Nunes and colleagues. And then the second key step for me would be the design of randomized controlled trials to test therapeutic agents with antitrypanosomal activity to demonstrate their ability to retard or completely block disease progression, which would be a nice way to complete the story. Dr. Greg Hundley:           Very nice. Well listeners, we've had a great discussion today and we want to thank Maria Nunes from Brazil and Ntobeko Ntusi from South Africa for bringing these really informative results pertaining to Chagas disease, and highlighting the natural history and showing an association between these high titer values and poor cardiovascular outcomes. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on The Run. This program is copyright of the American Heart Association, 2021. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit ahajournals.org.

A nighttime “kiss” from a bug that casts a curse on its recipient in the form of a lifelong, and possibly fatal, illness. No, this isn't some half-remembered fairy tale. It's the true story of Chagas disease, caused by the parasite Trypanosoma cruzi and transmitted by many species of triatomines (aka kissing bugs). In this episode, we take you through the utterly complicated biology of Chagas disease in its acute and chronic forms, the surprising evolutionary and historical background of this parasite and the scientist for whom it's named, and finally the grim reality that is the global status of Chagas disease today.  The dizzying ecological complexity and pathophysiological mystery of this disease makes it a challenge to study, and the lack of funding only compounds the issue; Chagas disease bears the dubious distinction of the most neglected of all the neglected tropical diseases. In spite of this, many people are dedicated to easing the global burden of Chagas disease, and we were delighted to interview two of these Chagas champions for this episode. Daisy Hernandez, Associate Professor at Miami University, joins us to discuss the inspiration for her recent book The Kissing Bug: A True Story of a Family, an Insect, and a Nation's Neglect of a Deadly Disease, and Dr. Sarah Hamer, Associate Professor at Texas A&M University, delves into the ecological aspects of this disease and shares the incredible community science program that raises awareness about T. cruzi and the bugs that transmit it. To learn more, check out the links below: Daisy Hernandez: website, Twitter (@daisyhernandez), Instagram (@iamdazeher), Facebook  Dr. Sarah Hamer: lab website, lab Twitter (@hamer_lab), Community Science Program See omnystudio.com/listener for privacy information.

TWiP solves the case of the Adventurous Eater with Areas of Swelling, and discusses an experimental Trypanosoma vivax vaccine comprising an invariant flagellum antigen. Hosts: Vincent Racaniello, Dickson Despommier, Daniel Griffin, and Christina Naula Download TWiP #197 (39 MB .mp3, 64 minutes) Subscribe (free): iTunes, Google Podcasts, RSS, email Links for this episode PWB on Facebook, Instagram, Twitter Experimental T. vivax vaccine (Nature) Letters read on TWiP 197 Become a patron of TWiP Case Study for TWiP 197 Gentleman in late 20s, has for weeks had watery diarrhea that is not getting better. Recently took trip to Oaxaca, Mexico. Stayed at nice hotel, all fruits, vegetables, salads well cleaned. Always ate at hotel. Developed diarrhea there. Went with three others, stayed at same place. No prior surgeries, no family history, no medications, no toxic habits. Daniel recommends one test and that gives diagnosis and therapy and he resolves.   Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

トリパノソーマのキネトコアについて話しました。Show notes トリパノソーマ キネトコア(動原体) セントロメア Misleading Chat 7. In the golden age of molecular biology (researchat.fm) … シドニー・ブレナー回 41. Single is not bad (researchat.fm) Akiyoshist … Akiyoshiさんファンの呼称 Akiyoshi Lab Bungo Akiyoshi ハルキスト Akiyoshi and Gull. Cell (2014) … Discovery of unconventional kinetochores in kinetoplastids Tromer et al., Open Biology (2021) … Repurposing of synaptonemal complex proteins for kinetochores in Kinetoplastida 体細胞分裂 (mitosis) 減数分裂 (meiosis) 2倍体 相同組換え 相同染色体 姉妹染色体 … sister chromatids コヒーシン シナプトネマコンプレックス double strand break … DNAの二本鎖が切断されること Spo11 Bloomfield. Annu Rev Microbiol (2018) … Dicty(キイロタマホコリカビ)はspo11がないが、減数分裂時に相同組換えを行う。 Cas9 DNAトポイソメラーゼ キアズマ … chiasma。chiasmaがない減数分裂のことをachiasmaと呼ぶ。 Rasmussen. Philos Trans R Soc Lond B Biol Sci. (1977) … “Meiosis in Bombyx mori females”: カイコのメスで見られるachiasmata John et al., Front Cell Dev Biol. (2016) … “Achiasmy: Male Fruit Flies Are Not Ready to Mix”: ハエのオスにおけるachiasmataに関する総説 Xia et al., Genome Biology(2007) … カイコの性細胞におけるspo11発現の論文(Additional Data 5) 48. XXXXXYYYYY (researchat.fm) … 性の多様性について。XYやZW型についても解説しています。 Garg and Martin. Genome Biol. Evol. (2016) … “Mitochondria, the Cell Cycle, and the Origin of Sex via a Syncytial Eukaryote Common Ancestor”: mitosisとmeiosisの進化について 水素仮説 William F Martin Muller's rachet 水平伝播(horizontal gene transfer) アフリカ睡眠病 ナガナ病 ツェツェバエ キネトプラスト キネトプラスト類(kinetoplastids) Benne et al., Cell (1986) … “ Major transcript of the frameshifted coxII gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA”: RNA editing in Trypanosoma Berriman et al., Science (2005)…The genome of the African trypanosome Trypanosoma brucei 中心体 微小管 ホモログ Ogbadoyi et al., Chromosoma (2000) … “Architecture of the Trypanosoma brucei nucleus during interphase and mitosis”: Trypanosomaのキネトコア様構造を電子顕微鏡で観察した論文 Peacock et al., Communications Biology (2021) … “Sequential production of gametes during meiosis in trypanosomes”: trypanosomaのmeiosisについて Weir et al., eLife (2021) … “Population genomics reveals the origin and asexual evolution of human infective trypanosomes”: asexual eukaryoteのTrypanosoma brucei gambienseについて(減数分裂がないというよりはsexがないというべき？) Déjardin and Kingston. Cell (2009) … “Purification of Proteins Associated with Specific Genomic Loci”: PICh法の論文 Thomas Cavalier-Smith LECA … The last eukaryotic common ancestor システム生物学 収斂進化 CENP-A Dinoflagellate… 渦鞭毛藻 Dinokaryon 無脊椎動物の発生 … 団勝磨先生ら著 ヒドロキシルメチルウラシル Talbert et al., The kinetochore (2009) … “Evolution of Centromeres and Kinetochores: A Two-Part Fugue” セントロメアとキネトコアの進化についての論文。Henikoff lab ファインマン デーモンコア プルトニウムは温かい What I cannot create, I do not understand. … 自分で作れないものは、理解していない。 Synthetic biology … 合成生物学 ツイート1 … EMBO, HSFP, Wellcome Trustによるサポート KKT1 uniprot Akiyoshi et al., Genes Dev. (2009) … Quantitative proteomic analysis of purified yeast kinetochores identifies a PP1 regulatory subunit Akiyoshi et al., Nature (2010) … Tension directly stabilizes reconstituted kinetochore-microtubule attachments 精製した動原体を用いた動原体とスピンドル微小管との結合の再構成 … 新着論文レビュー。秋吉さんの博士時代の論文解説 トリパノソーマのもつ型破りな動原体タンパク質の発見 … 新着論文レビュー。トリパノソーマのキネトコア論文の日本語解説 Sue Biggins Sue Biggins先生のインタビュー Sue Biggins先生のiBiology ドブジャンスキー 高井研 44. Tabasheer (researchat.fm) … 伊藤篤太郎、南方熊楠を含む、1800年代後半、Natureに投稿した日本人研究者について話しました。 Editorial notes 次のシリーズにも期待したいです (soh) 話し始めで構想からはずれてしまったため、アワアワしてしまいました。色々とっちらかってすいませんでした。次回チャンスがあればもう少しまとめられるようがんばります。(tadasu) キネトコアって名前かっこいい(coela)

The parasite Trypanosoma brucei is transmitted via tsetse flies. It causes a disease known as trypanosomiasis or sleeping sickness in humans, but in cows, it's known as nagana or animal African trypanosomiasis. In this episode, Joan Cortada García interviews Maria Contreras-Garcia from The Roslin Institute on her work to validate and characterize the use of a small RNA as a diagnostic test for trypanosomiasis.Here is a link to the event mentioned by Ruby White in our episode coda.  The event is a joint University of Edinburgh and University of Sydney Workshop Series on sustainable food production, antimicrobial resistance and One Health https://www.eventbrite.com.au/e/university-of-sydney-and-university-of-edinburgh-joint-workshop-series-2021-tickets-142438833385?utm_campaign=2889898_UoE-UoSyd%20OH%20workshops%20EID&utm_medium=email&utm_source=College%20of%20Science%20%26%20Engineering%2C%20The%20University%20of%20Edinburgh&dm_i=2MP0,1PXUY,9QQ8JI,5VOLI,1

Uma Pesquisa da Embrapa Amapá mostrou que a bebida de açaí (Euterpe oleracea Mart.) não sofre alterações no cheiro, textura e sabor se os frutos passarem por choque térmico de 80°C a 90°C. O choque é uma etapa essencial para inativação do Trypanosoma cruzi, causador da doença de Chagas, que pode estar presente em barbeiros contaminados. O estudo científico ouviu os relatos de consumidores do açaí tradicional da Região Norte e desmistificou o temor de que o calor alteraria as propriedades do alimento. Esse preconceito é uma das principais causas da rejeição do produto por parte da população e de alguns batedores, cujos frutos foram submetidos a tratamento térmico. A pesquisadora da Embrapa, Valéria Saldanha explica que o choque térmico nos frutos, ou branqueamento como é popularmente conhecido, elimina vários micro-organismos causadores de doenças, entre eles, o protozoário da doença de Chagas. Valeria Saldanha disse que os testes duraram dois dias com voluntários, que consomem açaí pelo menos uma vez por semana, degustaram a bebida e, em seguida, preencheram uma ficha de avaliação com perguntas socioeconômicas, impressão geral do produto e a intenção de compra. Participaram do ensaio sensorial 272 consumidores, homens e mulheres, que costumam a consumir o açaí. A maioria dos entrevistados (95,5%) aprovou o produto tratado termicamente, justificando apreciar as qualidades do que consideram o bom açaí: grosso e com cor, aroma e sabor característicos. Eles também afirmaram que comprariam o produto usado no ensaio, açaí médio preparado em batedeiras após os frutos serem tratados termicamente.

In today's VETgirl online veterinary CE podcast, we review Trypanosomiasis, or Chagas disease, which is caused by the protozoal parasite Trypanosoma cruzi. It is the most common cause of infectious myocarditis in humans. The primary means by which T. cruzi is transmitted is via introduction of feces from triatomine insects -; otherwise known as “Kissing” bugs -; into bug bites or mucous membranes, or ingestion of the bugs/feces themselves. It can also be transmitted from mother to fetus via the placenta. Not all humans or dogs that develop infection with T. cruzi experience clinical signs. Those that do may experience severe signs such as sudden death or chronic heart failure. The most common geographic region for T. cruzi infection in the United States is the southwest, particularly Texas, in part due to an abundant wild animal reservoir. Seroprevalence has been reported as far east as Virginia and Georgia.

This episode covers trypanosoma gambiense!

This episode covers trypanosoma cruzi!

Learn about whether parasites can turn us into zombies, why awkward silences are so awkward, and why bubbles form in boiling water. Could parasites turn us into zombies? By Cameron Duke Ahmed, I. (2019, November). The science of zombies: Will the undead rise? Phys.Org; Phys.org. https://phys.org/news/2019-11-science-zombies-undead.html Blum, J., Schmid, C., & Burri, C. (2006). Clinical aspects of 2541 patients with second stage human African trypanosomiasis. Acta Tropica, 97(1), 55–64. https://doi.org/10.1016/j.actatropica.2005.08.001 Flegr, J. (2007). Effects of Toxoplasma on Human Behavior. Schizophrenia Bulletin, 33(3), 757–760. https://doi.org/10.1093/schbul/sbl074 McAuliffe, K. (2012, February 6). How Your Cat Is Making You Crazy. The Atlantic. https://www.theatlantic.com/magazine/archive/2012/03/how-your-cat-is-making-you-crazy/308873/ Pappas, S. (2011, October 20). Unrelenting Sex Drive May Signal Deadly Rabies. Livescience.Com; Live Science. https://www.livescience.com/16627-sex-drive-rabies-infection.html Thomas, B. (2015, October 29). Meet the Parasites That Control Human Brains. Discover Magazine. https://www.discovermagazine.com/planet-earth/meet-the-parasites-that-control-human-brains The Science of Awkward Silences by Anna Todd Koudenburg, N., Postmes, T., & Gordijn, E. H. (2011). Disrupting the flow: How brief silences in group conversations affect social needs. Journal of Experimental Social Psychology, 47(2), 512–515. https://doi.org/10.1016/j.jesp.2010.12.006  Koudenburg, N., Postmes, T., & Gordijn, E. H. (2013). Resounding Silences. Social Psychology Quarterly, 76(3), 224–241. https://doi.org/10.1177/0190272513496794  Why do bubbles form in boiling water? by Ashley Hamer (Listener question from Abu) UCSB Science Line. (2020). Ucsb.Edu. http://scienceline.ucsb.edu/getkey.php?key=3197  Why Does Water Bubble When It Boils? (2019, November 2). Wonderopolis.Org. https://wonderopolis.org/wonder/why-does-water-bubble-when-it-boils Helmenstine, A.M. (2019). Know the Chemical Composition of Bubbles in Boiling Water. ThoughtCo. https://www.thoughtco.com/what-are-the-bubbles-in-boiling-water-4109061 Breslyn, W. (2016). Boiling, Atmospheric Pressure, and Vapor Pressure [YouTube Video]. In YouTube. https://www.youtube.com/watch?v=Ag4lLUXKuSM  ‌FAQ: Boiling and altitude/pressure. (2020). IAPWS.org. http://www.iapws.org/faq1/boil.html  Subscribe to Curiosity Daily to learn something new every day with Ashley Hamer and Natalia Reagan (filling in for Cody Gough). You can also listen to our podcast as part of your Alexa Flash Briefing; Amazon smart speakers users, click/tap “enable” here: https://www.amazon.com/Curiosity-com-Curiosity-Daily-from/dp/B07CP17DJY  See omnystudio.com/listener for privacy information.

Prof. Igor Cestari works with two parasites for the most part: Trypanosoma brucei and Trypanosoma cruzi, which respectively cause sleeping sickness and Chagas disease. He explains for listeners What scientists know about the progression of parasitic diseases in humans, How the lack of immune response to parasites is key to understanding how they survive in their host for so long, and How the combination of recent technology and science innovations, like CRISPR, will help curb infection rates.  Igor Cestari is an assistant professor in the Institute of Parasitology at McGill University in Montreal. He gives listeners a solid image of parasitic life cycles and host-parasite interactions as well as why they're such successful life forms. For example, initial parasitic infection symptoms often mimic a cold or flu and then disappear. Therefore, it's hard to know that one is infected until more damaging symptoms reveal themselves. He discusses the parasitic diseases known as sleeping sickness and Chagas disease most specifically and gives some reasons why the parasites that cause these diseases are so successful. Their ability to fool the immune system is one such reason, and while scientists understand some of these mechanisms, there's still much they don't know. He teaches listeners about two interesting parasitic tricks, namely their ability to coat themselves in some sugars from the host cell that then hides them from the immune system. Another parasite is able to change its coating to one that the immune system lets by its defenses. Some of these techniques make it challenging to create a vaccine to stop the parasites. However, Professor Cestari says that new genome sequencing platforms have really helped in these efforts. He believes that the future is promising because of utilizing combinations of genomics and proteomics that seem to be making headway in stopping these infections.  To learn more, see his website at McGill University: mcgill.ca/parasitology/faculty/igor-cestari. Available on Apple Podcasts: apple.co/2Os0myK

Dr. Juan Quintana is a postdoctoral research associate at the Wellcome Centre for Integrative Parasitology, and Institute of Biodiversity, Animal Health and Comparative Medicine at the University of Glasgow. He joins the show to talk about the research he's doing in the field of parasitology and host-parasite relationships. In this episode, you will learn: How African sleeping sickness is transmitted, and how it manifests in individuals who have been infected (in both the early and late stages of disease progression) How peptides play a role in quorum sensing in trypanosomes    Why it is difficult to treat this disease once it reaches the brain, and what sort of research is being done to find a good treatment In the MacLeod Lab at the University of Glasgow, Dr. Quintana's work is centered around Trypanosoma brucei, which is the parasite that causes African trypanosomiasis (commonly called African sleeping sickness). This human pathogen has plagued many people in Africa and has had a significant socioeconomic impact. During the first stages of infection, the parasite resides in the host's bloodstream, but eventually reaches the brain. Once it reaches the brain, circadian rhythm disturbances manifest (i.e. sleep during the day and insomnia at night). Left untreated, the disease is lethal. Dr. Quintana's goal is to better understand the mechanisms underlying infection, host-parasite interactions in the brain, and migration of the parasite from the blood to the brain tissues.  Ultimately, the hope is that a better understanding will lead to more effective diagnostic tests, treatment, and eventually eradication of the disease. He shares his expertise in the area where medical microbiology and parasitology intersect. He explains how transmission occurs through the bite of the tsetse fly, the life cycle of Trypanosoma brucei, the human immune response to infection, the ability of the parasite to hide in certain tissues and repopulate the blood, recent findings with regard to the metabolism of the parasite, and more. Follow Dr. Quintana on Twitter and explore his work at https://scholar.google.com/citations?user=kTSEeV8AAAAJ&hl=en. Available on Apple Podcasts: apple.co/2Os0myK

Tune in today to hear the Arthro-Pod gang discuss Chagas disease and kissing bugs. All the hosts have had questions asked of them about this disease and the insect that can help vector the causal parasite. There are lots of stories out there about the dangers but what is the truth about Chagas in much of the US? We'll cover the parasite, the disease, and kissing bugs like the eastern bloodsucking conenose in this episode!Triatoma infestans one of the important vectors of Chagas (Pest and Diseases Image Library , Bugwood.org) Show notesDisease: Chagas disease Parasite: Trypanosoma cruzi Reservoirs: Mammals Vectors: Triatomine bugs or kissing bugs  Reduviidae are a family otherwise known as assassin bugs that are Hemipterans. They have three segmented beak used to stab prey, which are mostly insects. According to Bug Guide, there are 195 species, 55 genera including wheel bug, jagged ambush bug, four spurred assassin bug (Zelus), masked hunter, and Sinea species (no common name)  Commonly misidentified non-reduviids: Western conifer seed bug, squash bugs,   Wheel bugs are often misidentified as kissing bugs (Photo by Jody Green)When people spot squash bugs they sometimes fear they are kissing bugs (photo by Jody Green)Kissing bugs Texas A&M - Kissing Bugs & Chagas Disease in the United States https://kissingbug.tamu.edu/ CDC – Chagas Disease https://www.cdc.gov/parasites/chagas/  PJ. Liesch from UW Madison Department of Entomology –  Comparison of eastern bloodsucking conenose and western conifer seed bug https://insectlab.russell.wisc.edu/2015/12/08/was-that-a-kissing-bug/ Comparison of eastern bloodsucking conenose with masked hunter https://insectlab.russell.wisc.edu/2019/07/31/masked-hunter-bugs/  Research papers: Bern et al. 2011 – Trypanosoma cruziand Chagas’ disease in the United States Klotz et al. 2014 – Kissing bugs in the United States: Risks for vector-borne disease in humans Salazar et al. 2015 – Bed bugs (Cimex lectularius) as vectors of Trypanosoma cruzi Questions? Comments? Follow the show on Twitter @Arthro_PodshowFollow the hosts on Twitter @bugmanjon, @JodyBugsmeUNL, and @MSkvarla36Get the show through Apple Podcasts!Subscribe to our feed on Feedburner!  We're also on Stitcher!This episode is freely available on archive.org and is licensed under Creative Commons: By Attribution 3.0. http://creativecommons.org/licenses/by/3.0/Beginning/ending theme: "There It Is" by Kevin MacLeod (incompetech.com) Licensed under Creative Commons: By Attribution 3.0

Hablamos con Andrés Cuervo, Profesional Especializado de Enfermedades de Transmisión por Vectores y Zoonosis de la Unidad De Salud junto al Dr. Rafael Erazo, Médico experto en Chagas. En la actualidad el departamento de Arauca se encuentra en el proceso de Certificación Internacional de Interrupción de la Transmisión Vectorial de Trypanosoma cruzi por Rhodnius prolixus Intradomiciliado, logrando la certificación de 5 municipios (Tame, Fortul, Saravena, Cravo Norte y Puerto Rondón, quedando pendientes los municipios de Arauca y Arauquita, para esto se continuar con un riguroso proceso de vigilancia epidemiológica, garantía de la atención y canalización de casos, acciones de control, vigilancia entomológica y fortalecimiento de la capacidad de gestión.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.19.211375v1?rss=1 Authors: Carter, M., Gomez, S., Gritz, S., Larson, S., Silva-Herzog, E., Kim, H.-s., Schulz, D., Hovel-Miner, G. A. Abstract: Trypanosoma brucei is an early branching protozoan parasite that causes human and animal African Trypanosomiasis. Forward genetics approaches are powerful tools for uncovering novel aspects of Trypanosomatid biology, pathogenesis, and therapeutic approaches against trypanosomiasis. Here we have generated a T. brucei cloned ORFeome consisting of over 90% of the targeted 7,245 genes and used it to make an inducible Gain-of-Function parasite library broadly applicable to large-scale forward genetic screens. We conducted a proof of principle genetic screen to identify genes whose expression promotes survival in melarsoprol, a critical drug of last resort. The 57 genes identified as overrepresented in melarsoprol survivor populations included the rate-limiting enzyme for the biosynthesis of an established drug target (trypanothione), validating the tool. In addition, novel genes associated with gene expression, flagellum localization, and mitochondrion localization were identified and a subset of those genes increased melarsoprol resistance upon overexpression in culture. These findings offer new insights into Trypanosomatid basic biology, implications for drugs targets, and direct or indirect drug resistance mechanisms. This study generated a T. brucei ORFeome and Gain-of-Function parasite library, demonstrated the libraries usefulness in forward genetic screening, and identified novel aspects of melarsoprol resistance that will be the subject of future investigations. These powerful genetic tools can be used to broadly advance Trypanosomatid research. IMPORTANCETrypanosomatid parasites threaten the health of over 1 billion people worldwide. Because their genomes are highly diverged from well-established eukaryotes, conservation is not always useful in assigning gene functions. However, it is precisely among the Trypanosomatid-specific genes that ideal therapeutic targets might be found. Forward genetics approaches are an effective way to identify novel gene functions. We used an ORFeome approach to clone a large percentage of Trypanosoma brucei genes and generate a Gain-of-Function parasite library. This library was used in a genetic screen to identify genes that promote resistance to the clinically significant, yet highly toxic drug, melarsoprol. Hits arising from the screen demonstrated the librarys usefulness in identifying known pathways and uncovered novel aspects of resistance mediated by proteins localized to the flagellum and mitochondrion. The powerful new genetic tools generated herein are expected to promote advances in Trypanosomatid biology and therapeutic development in the years to come. Copy rights belong to original authors. Visit the link for more info

Dr. Horn reviews several important tropical diseases, including Chagas disease (caused by Trypanosoma cruzii), spread by the Triatomid bug, African Trypanosomiasis, the cause of sleeping sickness, Cystercercosis, caused by the Pork tapeworm, and Buruli ulcer. He closes by discussing Onchocerciasis and its effect on significant areas of the developing world.

We are delighted today to have Ashley Hartley joining Bri and myself in the studio. Ashley is a staff clinician in internal medicine here at the RVC. Although she’d really like to talk about Trypanosoma cruzi infections we thought we’d speak about gallbladder mucoceles instead.  Ashley is passionate about all things to do with internal medicine, in particular infectious diseases, and we are grateful for her coming into the studio to share her thoughts today. We hope that you enjoy. Some papers of interest: https://www.ncbi.nlm.nih.gov/pubmed/29205503 https://www.ncbi.nlm.nih.gov/pubmed/31854510 https://www.ncbi.nlm.nih.gov/pubmed/31492387 https://www.ncbi.nlm.nih.gov/pubmed/31490022 https://www.ncbi.nlm.nih.gov/pubmed/30079451 If you have any comments about this podcast, please get in touch: email dbarfield@rvc.ac.uk; tweet @dombarfield. We would greatly appreciate your time to rate us on Apple podcast or Acast and kindly write us a review.

We are delighted today to have Ashley Hartley joining Bri and myself in the studio. Ashley is a staff clinician in internal medicine here at the RVC. Although she’d really like to talk about Trypanosoma cruzi infections we thought we’d speak about gallbladder mucoceles instead.  Ashley is passionate about all things to do with internal medicine, in particular infectious diseases, and we are grateful for her coming into the studio to share her thoughts today. We hope that you enjoy. Some papers of interest: https://www.ncbi.nlm.nih.gov/pubmed/29205503https://www.ncbi.nlm.nih.gov/pubmed/31854510https://www.ncbi.nlm.nih.gov/pubmed/31492387https://www.ncbi.nlm.nih.gov/pubmed/31490022https://www.ncbi.nlm.nih.gov/pubmed/30079451 If you have any comments about this podcast, please get in touch: email dbarfield@rvc.ac.uk; tweet @dombarfield. We would greatly appreciate your time to rate us on Apple podcast or Acast and kindly write us a review.

In this episode, we cover the oddball insect: the tsetse fly. Learn about its odd biology, hear about a parasitic disease it transmits, and listen to some of the different forms of vector control used to control it. Stick around as Bailey and Lindsay discuss the Wuhan coronavirus and its impact. Links to our Social Media Follow us on Instagram and Twitter @Infestedpodcast Follow Lindsay on Twitter @Baxter.Lindsay Email us at Infestedpodcast@gmail.com This Podcast is produced and edited by Lindsay and Bailey. Their views and opinions are theirs and do not reflect the institution for which they are employed References Cited   Angier, N. 2019. Everywhere in the Animal Kingdom, Followers of the Milky Way. New York Times. (https://www.nytimes.com/2019/02/11/science/milk-animals-evolution.html). Bhanoo, S. N. 2012. Tsetse Flies and Mammals Share a Milk Enzyme. New York Times. (https://www.nytimes.com/2012/04/24/science/tsetse-flies-and-mammals-share-a-milk-enzyme.html). Coren, M. J. 2020. China says the Wuhan virus, unlike SARS, is infectious during its incubation period. Quartz. (https://qz.com/1791405/china-says-wuhan-virus-unlike-sars-infectious-during-incubation/). De Meeûs, T., S. Ravel, P. Solano, and J. Bouyer. 2019. Negative Density-dependent Dispersal in Tsetse Flies: A Risk for Control Campaigns? Trends in Parasitology. 35: 615–621. Elliott, I., T. Patel, J. Shah, and P. Venkatesan. 2014. West-African trypanosomiasis in a returned traveller from Ghana: an unusual cause of progressive neurological decline. BMJ Case Rep. 2014. Franco, J. R., P. P. Simarro, A. Diarra, and J. G. Jannin. 2014. Epidemiology of human African trypanosomiasis. Clin Epidemiol. 6: 257–275. Gibson, W., L. Peacock, and R. Hutchinson. 2017. Microarchitecture of the tsetse fly proboscis. Parasites Vectors. 10: 430. Glossina CABI. 2020. Glossina. (https://www.cabi.org/isc/datasheet/102385). Hide, G. 1999. History of Sleeping Sickness in East Africa. Clin. Microbiol. Rev. 12: 112–125. International Society for Antiviral Research - Coronavirus 19-20 Outbreak . 2020. International Society for Antiviral Research - Coronavirus 19-20 Outbreak. (https://www.isar-icar.com/Coronavirus). Krafsur, E. S. 2009. Tsetse flies: Genetics, evolution, and role as vectors. Infect Genet Evol. 9: 124–141. Lambrecht, F. L. 1980. Palaeoecology of Tsetse Flies and Sleeping Sickness in Africa. 20. McNeil Jr., D. G. 2018. Rapid Cure Approved for Sleeping Sickness, a Horrific Illness - The New York Times. New York Times. (https://www.nytimes.com/2018/11/16/health/sleeping-sickness-africa-cure.html). New York Times. 2020. Alarm Grows as Markets Tumble and Death Toll Rises - The New York Times. New York Times. (https://www.nytimes.com/2020/01/27/world/asia/china-coronavirus.html). Novel Coronavirus 2019, Wuhan, China | CDC Centers for Disease Control. 2020. Novel Coronavirus 2019, Wuhan, China | CDC. (https://www.cdc.gov/coronavirus/2019-ncov/index.html). Shaw, A. P. M., S. J. Torr, C. Waiswa, G. Cecchi, G. R. W. Wint, R. C. Mattioli, and T. P. Robinson. 2013. Estimating the costs of tsetse control options: An example for Uganda. Preventive Veterinary Medicine. 110: 290–303. Slingenbergh, J. 2020. Tsetse control and agricultural development in Ethiopia. FAO. (http://www.fao.org/ag/aGA/AGAP/FRG/FEEDback/War/u6600b/u6600b0g.htm). Trypanosoma sp. Protozoa - MONSTER HUNTER’S GUIDE TO: VETERINARY PARASITOLOGY Veterinary Pathology. 2020. Trypanosoma sp. Protozoa - MONSTER HUNTER’S GUIDE TO: VETERINARY PARASITOLOGY. https://www.veterinaryparasitology.com/trypanosoma.html.

Ao descobrir o Trypanosoma cruzi na região de Lassance, Carlos Chagas abre um novo capítulo para a ciência brasileira e para a compreensão da realidade social do país.

Some monsters live inside us. PhD candidate in Biological Sciences in Public Health Maddy McFarland studies Trypanosoma cruzi, a parasite that transforms its shape to sneak inside our cells and makes us sick. The scariest part: Our cells can’t signal that they’re infected until it’s too late.Full TranscriptThe Veritalk Team:Host/Producer: Anna Fisher-PinkertExecutive Producer: Ann HallSound Designer: Ian CossLogo Designer: Emily CrowellSpecial thanks to the lab of Barbara Burleigh, professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, and to the National Institutes of Health, which funds the research of the Burleigh lab.Originally released in 2018.

No episódio de hoje do Microbiando, vamos mostrar o caminho que o T. cruzi faz pelo organismo quando a contaminação é oral. Para isso, vamos analisar o artigo "Desvendando a transmissão da doença de Chagas pela via oral: Portas para a infecção pelo Trypanosoma cruzi e tecidos-alvo", publicado por um grupo da Fiocruz/RJ em 2017. No Microlitros de notícias apresentaremos uma possível associação entre microorganismos e a endometriose; além do cultivo de arquéias em laboratório. E No filogenia da ciência, temos a vida do microbiologista Salvatore Luria explorada a fundo Observação: Toda vez que a doida da Adriana fala mosquito, ouça percevejo. (Palavras da própria) Imagem do barbeiro na capa do episódio é do acervo Fiocruz Imagens. Sobre o Podcast Microbiando A ideia do Microbiando é discutir artigos científicos de ponta em todas as áreas da microbiologia e imunologia. Vamos utilizar uma linguagem bem acessível para destrinchar esses artigos para vocês, mas sem perder o rigor científico e analítico necessário para essa tarefa. Além de discutir artigos nós teremos o quadro Microlitros de Notícias, onde nossos microbiologistas e imunologistas de plantão irão abordar pequenas reportagens e trazer novidades para vocês. No quadro filogenia da Ciência vamos contar um pouco sobre a vida de grandes personalidades que revolucionaram a Microbiologia e Imunologia com suas descobertas. Você pode nos ouvir no Spotify, Google Podcast, Deezer, Stitcher, Player FM, Podcast Addict, CastBox, Blubrry Podcasting, iTunes e outros aplicativos de podcasts. Contatos E-mail: microbiando@micro.ufrj.br TwitterFacebookInstagram O podcast Microbiando tem o apoio do Instituto de Microbiologia Professor Paulo de Góes e do Instituto de Biofísica Carlos Chagas Filho, ambos da UFRJ. Além da Sociedade Brasileira para o Progresso da Ciência, da Sociedade Brasileira de Imunologia, da Sociedade Brasileira de Microbiologia, da Sociedade Brasileira de Virologia, do Marketplace iBench e do site de divulgação científica A Ciência Explica. Apoiadores do A Ciência Explica Leandro LoboGabriel SiqueiraMasashi C. InoueCelia Campos Tobaldini-MansbachEduarda Moura Obrigado por nos apoiarem através do financiamento coletivo! Apoie você também e ganhe recompensas, como canecas, bottons, adesivos e livros exclusivos. Não pode ajudar financeiramente? Siga nossas redes sociais e compartilhe nossas matérias com seus amigos!

Florencia Irigoín es doctora en química, docente e investigadora del Departamento de Histología y Embriología de la Facultad de Medicina (Udelar) y del Laboratorio de Genética Molecular Humana del Institut Pasteur de Montevideo. Durante su carrera científica trabajó como investigadora en varias áreas vinculadas a la microbiología y bioquímica, estudiando el parásito que produce la hidatidosis, y el Trypanosoma cruzi, que produce la enfermedad de Chagas. Actualmente, Irigoín trabaja en biología celular, apuntando a entender el funcionamiento de las células de nuestro cuerpo. Su línea de investigación específica es el estudio de la denominada “cilia primaria”, una parte de la célula cuyo mal funcionamiento se viene asociando a diversas enfermedades humanas llamadas “ciliopatías”.

Dr. Norma Andrews overviews the mechanisms of cellular plasma membrane repair. As she describes, a lesion is followed by a Ca2+-dependent movement of vesicles to the plasma membrane. By studying how the Trypanosoma cruzi parasite enters the cell, Andrews' laboratory discovered that an increase of intracellular calcium was triggering lysosomal fusion to the plasma membrane. This unexpected observation allowed them to conclude that upon an injury to the plasma membrane, a Ca2+ influx induces lysosomal exocytosis mediated repair. This research demonstrates that lysosomes are not only responsible for the degradation of material that comes inside the cell through endocytosis, but also have an important role in plasma membrane repair.

The TWiPlicates solve the case of the Child With Retinal Granuloma, and discuss an association of the complement protein collectin-11 with the pathophysiology of Chagas disease. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiP. Links for this episode: Chagas disease pathophysiology and collectin-11 (PLoS NTD) Hero: Theobald Smith Image credit: Toxocara canis by Ben Liffner Letters read on TWiP 170 Case Study for TWiP 170 3 yo girl, same context: mobile clinic in Bocas del Toro archipelago. Small village on remote island. Initially had red eye, rubbing a lot, mother noticed she seemed to have vision loss. On exam ophthalmologist did fundoscopic exam, sees band keratopathy, calcium on the cornea, and outer retinal punctate lesions. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

No episódio de hoje vamos discutir sobre a relação entre o Trypanosoma cruzi e o tecido adiposo. Sobre o Podcast Microbiando A ideia do Microbiando é discutir artigos científicos de ponta em todas as áreas da microbiologia e imunologia. Vamos utilizar uma linguagem bem acessível para destrinchar esses artigos para vocês, mas sem perder o rigor científico e analítico necessário para essa tarefa. Além de discutir artigos nós teremos o quadro Microlitros de Notícias, onde nossos microbiologistas e imunologistas de plantão irão abordar pequenas reportagens e trazer novidades para vocês. No quadro filogenia da Ciência vamos contar um pouco sobre a vida de grandes personalidades que revolucionaram a Microbiologia e Imunologia com suas descobertas. Você pode nos ouvir no Spotify, Google Podcast, Player FM, Podcast Addict, CastBox, Blubrry Podcasting, iTunes e outros agregadores de podcasts. Contatos E-mail: microbiando@micro.ufrj.br TwitterFacebookInstagram Expediente Produção Geral: Adriana CabanelasEquipe de Pauta/Gravação: Adriana Cabanelas, Ana Carolina Oliveira, Gabriel Martins, Vitória Fernanda, Juliana Echevarria, Rosana FerreiraEdição: Hugo Marins/NNOTEM (Núcleo de Novas Tecnologias e Mídias/IBCCF)Trilha Sonora: Daniel Vasquez O podcast Microbiando tem o apoio do Instituto de Microbiologia Professor Paulo de Góes e do Instituto de Biofísica Carlos Chagas Filho, ambos da UFRJ. Além da Sociedade Brasileira para o Progresso da Ciência, da Sociedade Brasileira de Imunologia, da Sociedade Brasileira de Microbiologia, da Sociedade Brasileira de Virologia, do Marketplace iBench e do site de divulgação científica A Ciência Explica. Apoiadores do A Ciência Explica Leandro LoboGabriel SiqueiraCarlos Eduardo da Silva Obrigado por nos apoiarem através do financiamento coletivo! Apoie você também e ganhe recompensas, como canecas, bottons, adesivos e livros exclusivos. Não pode ajudar financeiramente? Siga nossas redes sociais e compartilhe nossas matérias com seus amigos!

The Podfessors solve the case of the Teenager With Swollen Scrotum, and continue the story arc of Daniel's favorite cells, B-1 cells, and their association with protective immune responses in human Chagas disease. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiP. Links for this episode: B1 cells and Chagas disease (Front Immunol) Daniel discovers B1 cells (J Exp Med) Hero: Bridget Ogilvie Image credit Letters read on TWiP 166 Case Study for TWiP 166 Recent consult from gastroenterologist. 61 yo woman on trip to Thailand, Cambodia for a few weeks. Developed diarrhea, took azithromycin, 3 days. Diarrhea continued, back in states now ongoing a few weeks. Left lower abdominal pain, bloated, gassy, loose stools, stick and foul smelling. Not sexually active, but is relevant. Not restrictive in what she ate. Drank bottled water. Did not eat raw items. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

The TWiP legends solve the case of Surfer Sans Septum, and discuss how two symbiotic bacteria in the tsetse fly allow colonization with Trypanosoma brucei. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiP. Links for this episode: A Tale of Three Species (mBio) V.B. Wigglesworth (Wikipedia) VB Nimble, VB Quick Hero: James Paget Letters read on TWiP 164 Case Study for TWiP 164 Welcome to Uganda. Mother brings in 4 yo female child, end of rainy season, concerned that has one day of fever, headache, cough. On exam looks ill, unremarkable except rapid heart rate, localized crackles in right lower lung. Several children in family. Spends day swimming in local stream. Take care of animals. Help gather drinking water in morning. Live in dirt floor home, thatch roof, with animals around. Saw many others with same problem. What tests do you want to do? Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

Esta es la historia de una enfermedad olvidada y silenciosa. La enfermedad de Chagas, como muchas otras, es “olvidada” porque, aunque mate a 10.000 personas en el mundo anualmente, aún hay poca investigación, no está en la agenda de los gobiernos o simplemente no es rentable para la industria farmacéutica. En la mayoría de los casos, infectarse con el parásito que la causa, el Trypanosoma cruzi, es desapercibido. Según estimativos del Centro de Investigaciones en Parasitología Tropical (CIMPAT) de la Universidad de los Andes, en Colombia hay un millón de infectados. Es una enfermedad silenciosa, porque sus efectos pueden sentirse años después de contraer el parásito. Efrito y Pardito hablan con investigadores del CIMPAT para saber más sobre la enfermedad, el parásito y el insecto que se encarga de esparcirla desde el sur de Estados Unidos hasta Argentina.

The TWiP professors solve the case of the Baby With Pericardial Effusion, and discuss whether the flagellate without a flagella, Dientamoeba fragilis, causes human illness. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiP. Links for this episode: Patients with Dientamoeba fragilis infection (Am J Trop Med Hyg) Hero: Dr. Eloise B. Cram Image credit Letters read on TWiP 162 Case Study for TWiP 162 A fresh case. Woman in late 30s born in Palestine, moved to NY. Presented for care with sore throat, swollen lymph nodes. Married Lebanese man, he’s still there, travel back in forth. Had been in Lebanon for 3 weeks before illness. Ate special raw meat dish while in Lebanon. No other animal exposure. Small children at home, works in office. No medical/surgical history, no meds. On exam, has posterior cervical lymphadenopathy. Otherwise normal exam. HIV negative. Low grade fever. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

The TWiPsters solve the case of the Brazilian Immigrant With Heart Problems, and describe how genome organization controls trypanosome antigenic variation. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiP. Links for this episode: Trypanosome genome organization and antigenic variation (Nature) Hero: Arthur Looss Letters read on TWiP 161 Case Study for TWiP 161 Daniel was asked to see 30 yo female from Bolivia, had to travel back during 3rd trimester. Was there for most of 3rd trimester. Child born in US, pericardial effusion, ascites, moderate PDA. Heart function is ok. Woman was healthy, no issues during pregnancy. Baby’s  white count elevated, diagnostic evaluation. It is a parasite. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

Esta es la historia de una enfermedad olvidada y silenciosa. La enfermedad de Chagas, como muchas otras, es “olvidada” porque, aunque mate a 10.000 personas en el mundo anualmente, aún hay poca investigación, no está en la agenda de los gobiernos o simplemente no es rentable para la industria farmacéutica. En la mayoría de los casos, infectarse con el parásito que la causa, el Trypanosoma cruzi, es desapercibido. Según estimativos del Centro de Investigaciones en Parasitología Tropical (CIMPAT) de la Universidad de los Andes, en Colombia hay un millón de infectados. Es una enfermedad silenciosa, porque sus efectos pueden sentirse años después de contraer el parásito. Efrito y Pardito hablan con investigadores del CIMPAT para saber más sobre la enfermedad, el parásito y el insecto que se encarga de esparcirla desde el sur de Estados Unidos hasta Argentina. Queremos agradecer a Luz Amparo Fonseca y a todos nuestros Patreons por permitirnos seguir contando la ciencia. -Apóyanos en Patreon: www.patreon.com/shotsdeciencia -O apóyanos con una donación en www.ciencialegible.com/apoyanos

Some monsters live inside us. PhD candidate in Biological Sciences in Public Health Maddy McFarland studies Trypanosoma cruzi, a parasite that transforms its shape to sneak inside our cells and makes us sick. The scariest part: Our cells can’t signal that they’re infected until it’s too late. Full Transcript The Veritalk Team: Host/Producer: Anna Fisher-Pinkert Executive Producer: Ann Hall Sound Designer: Ian Coss Logo Designer: Emily Crowell Special thanks to the lab of Barbara Burleigh, professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, and to the National Institutes of Health, which funds the research of the Burleigh lab.

Transmitted by the bite of the tsetse flu (Glossina spp.), African trypanosomiasis, of sleeping sickness is a serious infection caused by microscopic parasites of the species Trypanosoma brucei. Although the infection is not found in the United States, historically, it has been a serious public health problem in some regions of sub-Saharan Africa. In 2014, 3,796 sleeping sickness cases were reported to the World Health Organization; T. b. gambiense accounted for >98% of cases. Many cases, however, are probably not recognized nor reported. I recently had a long conversation with Associate Professor of Infectious Disease and International Medicine at USF Health, Sandra Gompf, MD about a myriad of infectious disease topics from her handy book, Gompf's ID pearls and one on the topics I asked her about was African sleeping sickness.

The parasitic infection, Chagas disease, was first discovered in 1909 by Brazilian physician Carlos Chagas. According to the World Health Organization, an estimated more than 10,000 people die every year from clinical manifestations of Chagas disease, and more than 25 million people risk acquiring the disease. It is caused by the parasite Trypanosoma cruzi, and the disease is also referred to as American trypanosomiasis. Hutchinson Distinguished Professor of Biological Sciences at Loyola University New Orleans, Patricia Dorn, PhD joined me to discuss Chagas disease and her class trip to Guatemala.

The TWiP-tastic peeps solve the case of the Thai Man Coughing Up Blood, and reveal potential therapies for trypanosomiasis that are inhibitors of protein import into glycosomes. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Become a patron of TWiP. Links for this episode: Inhibitors of protein import into trypanosome glycosomes (Science) Hookworm (TWiP #22) Photo by Nita Letters read on TWiP 132 Case Study for TWiP 132 Young NYC woman with son (10), chief complaint of discomfort and itchiness in anal area. Has tried to look but nothing abnormal. Married, no complaints from husband or child. Two older kids have no complaints. But son has also been scratching in anal area. Everything fine 3 months ago, sister came to visit with 3 young pre-school children, may have caught something from them. No past med or surg history, no allergies. No meds, work out of home, no toxic habits, no recent travel. Have dog. Do lots of volunteering with children. History of sushi consumption. She does not like raw fish but son does. Worse itching at night. Going on for a number of weeks. Reports being under a lot of stress recently due to family. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The TWiPniks solve the case of the Man With AIDS, and explore how secretion of extracellular vesicles influences the social motility of Trypanosoma brucei. Become a patron of TWiP. Links for this episode: T. brucei exosomes and social motility (PLoS Path) Image credit Parasites Without Borders Letters read on TWiP 130 This episode is brought to you by Blue Apron. Blue Apron is the #1 fresh ingredient and recipe delivery service in the country. See what’s on the menu this week and get your first 3 meals free with your first purchase - WITH FREE SHIPPING - by going to blueapron.com/twip. Case Study for TWiP 130 Back in Peru. 24 yo female seen in ER, lives in rural area outside of big city, adobe house in highlands, thatched roof, dirt floor, 3000 meters. Quite ill with skin lesion for 48 h. 2 days before was pulling on pjs, felt sharp sudden pain in right upper leg. Next day found small living creature in pajamas, inguinal region. Developed red lesion, enlarged, developed black central dot. Then begins vomiting, comes to hospital. No fever, breathing fast 20, hr 70, bp 160/10, on exam see in right inguinal region an enlarging, necrotic area 1-2 cm, starting to look sick. Whites at 26000, left shift, 200 platelets, eosinophils 4%, bilirubin 3.5, creatinine 4.9 (going into renal failure, not making much urine). Hematocrit 14, BUN 59.7, CPK 227, RBCs and leukocytes in urine. No health problems, no surgeries, first interaction with health system. No toxic habit. Brings in the small creature! Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The prolific podcast-shedding Hosts solve the case of the Global Health Intern with a snakelike lesion on her foot, and reveal the role of a single-stranded DNA binding protein in differentiation of trypanosomes. Become a patron of TWiP. Links for this episode: RPA protein and differentiation of T. cruzi (PLoS NTD) Image credit Letters read on TWiP 124 Case Study for TWiP 124 28 yo male from referral hospital near thai-burma border. Fever and chills 2 days, feels poorly, small amount of dark urine. Severe shaking chills, 1x per day, no rash. No diarrhea, difficulty breathing. Seen by local health care volunteer, went to hospital then tertiary hospital in Bangkok. Exposure history to pigs, dogs, insects, etc. Involved in timber industry and farming, sleeping out at night with no cover, clothes and sandals. No meds. Not married, family lives with him. Family is fine. Sleep in dwelling but no screens. No toxic habits, HIV negative, sexually active but not brothels. High fever, low bp, rapid heart rate, breathing rapidly, scleral icterus, dry mucus membranes, neck supple, lungs clear. 2/6 systolic murmur. Abdomen soft but tender, enlarged liver and spleen. Many cuts, bruises, bug bites. Labs: low platelets, low hematocrit, low glucose. Blood smear: abnormal, 5-10% infected RBCs with multiple band forms.  Send your case diagnosis, questions and comments to twip@microbe.tv

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The TWiPanosome docs solve the case of the Mali Man with Profuse Diarrhea, and review the presence of Trypanosoma cruzi in vectors, canids, and humans along the Texas-Mexico border. Become a patron of TWiP. Links for this episode: T. cruzi in vectors, canids, humans at Mexican border (PLoS NTD) Tetracapsuloides bryosalmonae (Wikipedia) T. cruzi in US (Clin Micro Rev) Image credit Letters read on TWiP 121 This episode is sponsored by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and non­fiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/microbe and use the promo code MICROBE. Case Study for TWiP 121 Back to Peru. 55 yo female from highland central valley area near Cuzco. Works in farming, no prior skin lesions but has multiple hypopigmented scars on exposed extremities (trauma during working), now reports many years of bloody nasal discharge. Seen in Lima by Daniel in outpatient clinic. No other medical problems, no surgeries, no allergies, everyone in family fine, husband and kids. Still working. No travel except to see doctor. Exam in right nare: ulcerated lesion inside nose, muco-cutaneous lesion. Simple test will decide. No anemia, no fever. Not eosinophilic, labs normal, HIV negative. Send your case diagnosis, questions and comments to twip@microbe.tv

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The TWiP triumvirate solve the case of the Thai Woman with Facial Swelling, and explain how Th17 T cells protect against the intracellular parasite Trypanosoma cruzi. Become a patron of TWiP. Links for this episode: Th17 cells protect against Trypanosoma cruzi (PLoS Path) Plasticity of helper CD4+ cells (Science) Image credit Letters read on TWiP 120 This episode is sponsored by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and non­fiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/microbe and use the promo code MICROBE. Case Study for TWiP 120 A 48 yo man from Mali comes to hospital ER in Washington Heights in NY with profuse watery diarrhea. Born in Mali, came to US at 18, working in US as long haul truck driver for 30 y, frequently visits Mali, recently to attend his father’s funeral. Got symptoms one week after return (was there for 3 weeks). 3 liters diarrhea/day. No past med/surg history, not seen doctor in long time. No allergies. Unknown what father died of, Mother in Mali is ok. No medications. Some alcohol, marijuana use. Does report that has exposure to professional female sex workers, no condoms. Temp of 39 C, bp down 80/40, heart over 110, rapid breathing high 20s, cachectic. Wasted. Fungating lesion perianally. Undergoes HIV testing, clade B. T cells

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin The TWiPtoids solve the case of the Thai Fisherman with Chronic Diarrhea, and reveal a potential new drug for treatment of leishmaniasis, Chagas diseases, and sleeping sickness. Links for this episode: Capillaria philippensis (Wikipedia) Proteasome inhibitor for three parasitic diseases (Nature) Image credit Letters read on TWiP 116 This episode is sponsored by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and non­fiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/microbe and use the promo code MICROBE. This episode is also sponsored by Drobo, a family of safe, expandable, yet simple to use storage arrays. Drobos are designed to protect your important data forever. Visit www.drobo.com to learn more. Become a patron of TWiP. Case Study for TWiP 116 This week's case involves no math. 36 year old Thai man from the northeast part of the country. Comes in with abdominal distention. Eats a normal Thai diet - Som Tam, Koi Pla, lots of rice. Feels well, came in because he is getting yellowing of skin and whites of eyes - jaundiced. Previously healthy, no prior med prob or surgery. No diseases running in family. Fisherman in the northeast (freshwater). Wife and many children, monogamous, HIV negative. Lives in jungle area, near river, many dogs, chickens, monkeys, goats, cows, pigs. Bathroom is outside. No fever, thin. Distention going on for months. Getting bigger. Exam: jaundiced, has large palpable non-tender mass below liver on his right side. No enlarged liver or spleen. No travel.  Send your case diagnosis, questions and comments to twip@microbe.tv

Hoy tenemos la suerte de contar con la compañía de Michael Z. Levy, Catedrático Asistente de Epidemiología en el Departamento de Bioestadística y Epidemiología de la Universidad de Pennsylvania, EE.UU. Michael ha sido un incansable trabajador en el area de control/eliminación del vector del mal de chagas.  Con varios años de esfuerzos en las áreas de alta prevalencia, Peru, Bolivia, Argentina y Brasil, Michael tiene muchas gratas experiencias en esta area.  En este episodio discutimos varios aspectos de este "patógeno olvidado" y su importancia social y de salud pública. Inscribѐse al Mundo de los Microbios con iTunes, RSS, email. recursos:  Bed Bugs (Cimex lectularius) as Vectors of Trypanosoma cruzi (pdf)   Epidemiology of and Impact of Insecticide Spraying on Chagas Disease in Communities in the Bolivian Chaco (pdf)

Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Guest: Michael Libman Michael returns to help the TWiP trio solve the case of the Delusional African Expatriate, and discuss the association of natural and induced antibodies in mice with differential susceptibility to secondary cystic echinococcosis. Links for this episode: T. brucei life cycle (pdf) Natural and induced antibodies in echinococcosis (Immunobiol) The collaborative cross Letters read on TWiP 104  Case study for TWiP 104 This week's case involves a young man in his thirties, admitted in hospital in Anchorage AK in early June. Chief complaint, severe muscle pain and tenderness. Usually healthy guy, 1 week ago had bad case of diarrhea with belly pain and vomiting, lasted a full week. Now has fever. Concerned because wife now is having diarrhea. Unremarkable history, unknown family history. HIV negative. All childhood vaccinations. Does not eat raw meat. No meds, does seasonal work, social drinker. Came back from successful hunt, got a black bear. Dressed in field, cooked at home really well. Wife also ate bear meat. Bear meat is in freezer. No vegetables. Also eats salmon which he caught the previous season, then frozen. Drinks water from the stream when he hunts. Physical exam: hot, 38.5, bp 115/75, pulse 105, breathing comfortably. Anxious, swelling around both eyes. Sclera not noted. Labs: WBC elevated 14,000, 30% eosinophils; chemistries fine; muscle enzymes LDH, CK elevated. Send your diagnosis to twip@microbe.tv Send your questions and comments to twip@microbe.tv

Flossing teeth: we all do it—or think we should do it—but is it scientific? Numerous scientific studies say flossing your teeth won't prevent tooth decay, and mouthwash may be just as good or better.Asexual organisms (that got your attention) are subject to the Meselson effect, in which genes on separate chromosomes evolve separately. And this could eventually cause Trypanosoma brucei gambiense—the parasite that causes African sleeping sickness—to go extinct.Speaking of diseases to worry about, we talk to virologist Ian Mackay about the mosquito-borne global health emergency, the Zika virus. Is it time to panic? Eh...

Vincent, Dickson, and Daniel discuss how fluctuation in the price of guinea pig food could help transmission of the agent of Chagas disease, and present a new case study for your consumption. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Links for this episode: Ascaris on TWiP 21 Ascaris lumbricoides life cycle (jpg) Child with distended abdomen due to Ascaris (jpg) Bottlenecks and Chagas disease (Proc Biol Soc) Letters read on TWiP 92 Case study for TWiP 92 A 20 yo Japanese female student went to the emergency room with severe abdominal pain. nausea, had vomited. Had just enjoyed homemade sushi an hour or two previuosly. She prepared the sushi: rice, salmon, tuna rolls. Salmon was local, caught by boyfriend. Tuna from store, sushi grade. No past medical history, mother with anemia. Takes oral contraceptives. No toxic habits. No travel. Monogamous. Temp 100.2, bp 140/90, hr high 90s, breathing upper teens. Physical exam normal except appears distressed in pain, belly extended, tender in left upper quadrant. Friends ate sushi but no one else got sick. All guests ate both types of fish. Send your diagnosis to twip@twiv.tv Contact Send your questions and comments (email or mp3 file) to twip@twiv.tv Subscribe Subscribe to TWiP (free) in iTunes, by the RSS feed or by email

Thu, 18 Sep 2014 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/18834/ https://edoc.ub.uni-muenchen.de/18834/1/Allmann_Stefan.pdf Allmann, Stefan ddc:570, ddc:500, Fak

Shulamit Michaeli talks about how the Trypanosoma brucei kinase PK3 inhibits new protein production in response to endoplasmic reticulum stress.

Hosts: Vincent Racaniello Dickson Despommier, and Sagi Shapira Vincent, Dickson, and Sagi discuss evidence that the pathogen Trypanosoma brucei undergoes meiosis and sexual reproduction. Links for this episode: Meiosis and haploid gametes in T. brucei (Curr Biol) Meiosis (Wikipedia) Letters read on TWiP 68 Contact Send your questions and comments (email or mp3 file) to twip@twiv.tv Subscribe Subscribe to TWiP (free) in iTunes, by the RSS feed or by email

Hosts: Vincent Racaniello and Dickson Despommier Vincent and Dickson discuss reversible inhibitors of cruzipain as new drugs for treating Chagas disease. Links for this episode: Reversible cysteine protease inhibitors for Chagas (AAC) New drug candidates for Chagas (ScienceDaily) Pancake ice (YouTube) Letters read on TWiP 66 Contact Send your questions and comments (email or mp3 file) to twip@twiv.tv Subscribe Subscribe to TWiP (free) in iTunes, by the RSS feed or by email  

Mon, 3 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15127/ https://edoc.ub.uni-muenchen.de/15127/1/Gassen_Alwine.pdf Gassen, Alwine

Vincent and Dickson review how sickle cell microRNAs contribute to malaria resistance, and inhibition of innate immune responses by an enzyme from trypanosomes. Links for this episode: microRNAs involved in sickle cell resistance to Plasmodium (Cell Host Microbe) Trypanosome adenylate cyclases modulate innate immune response (Science) Letters read on TWiP 43 Contact Send your questions and comments (email or mp3 file) to twip@twiv.tv.

Felipe Guhl Nanneti es colombiano, nacido en Bogotá.  Estudió biología y microbiología en la Universidad de los Andes en Bogotá y tiene grados avanzados en parasitología tropical, de la misma universidad. Desde hace más de 30 años es profesor en la facultad de ciencias de esa institución y se ha dedicado también a la investigación; su principal área de interés es el estudio de las enfermedades tropicales, principalmente la enfermedad de Chagas; ha realizado múltiples investigaciones sobre Trypanosoma cruzi el agente etiologico de esta enfermedad asi como sobre la ecología del vector y los factores de riesgo asociados a la transmisión de esta enfermedad. También ha estudiado ampliamente la historia de la presencia y la dispersión del Chagas en las culturas precolombinas de América. Felipe Guhl dirige el Centro de Investigaciones en Microbiología y Parasitología Tropical o CIMPAT por sus siglas y durante los pasados dos años presidió la Federación Latinoamericana de Parasitología.

Background: The essential purine salvage pathway of Trypanosoma brucei bears interesting catalytic enzymes for chemotherapeutic intervention of Human African Trypanosomiasis. Unlike mammalian cells, trypanosomes lack de novo purine synthesis and completely rely on salvage from their hosts. One of the key enzymes is adenosine kinase which catalyzes the phosphorylation of ingested adenosine to form adenosine monophosphate (AMP) utilizing adenosine triphosphate (ATP) as the preferred phosphoryl donor. Methods and Findings: Here, we present the first structures of Trypanosoma brucei rhodesiense adenosine kinase (TbrAK): lthe structure of TbrAK in complex with the bisubstrate inhibitor P(1),P(5)-di(adenosine-5')-pentaphosphate (AP5A) at 1.55 angstrom, and TbrAK complexed with the recently discovered activator 4-5-(4-phenoxyphenyl)-2H-pyrazol-3-yl]morpholine (compound 1) at 2.8 angstrom resolution. Conclusions: The structural details and their comparison give new insights into substrate and activator binding to TbrAK at the molecular level. Further structure-activity relationship analyses of a series of derivatives of compound 1 support the observed binding mode of the activator and provide a possible mechanism of action with respect to their activating effect towards TbrAK.

Vincent and Dickson discuss the life cycle and pathogenesis of the protozoan parasite Trypanosoma. Host links: Vincent Racaniello and Dickson Despommier Links for this episode: Metacyclic trypanomastigote (jpg) Tsetse fly (jpg) T. brucei life cycle (jpg) T. brucei parasitemia (jpg) Kissing bug nymph (jpg) T. cruzi life cycle (jpg) Letters read on TWiP 15

Thu, 1 Jul 2010 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17311/ https://edoc.ub.uni-muenchen.de/17311/1/Brenndoerfer_Martin.pdf Brenndörfer, Martin ddc:570, ddc:500, Fakultät für

Special Issue "Renal and urinary proteomics", Proteomic Strategies in Bladder Cancer: From Tissue to Fluid and Back, Renal cyst fluid proteome, Proteomics in Trypanosoma cruzi, Reports, Proteomic analysis in assisted reproductive technologies

Special Issue "Renal and urinary proteomics", Proteomic Strategies in Bladder Cancer: From Tissue to Fluid and Back, Renal cyst fluid proteome, Proteomics in Trypanosoma cruzi, Reports, Proteomic analysis in assisted reproductive technologies

The protozoan parasite Trypanosoma brucei causes human sleeping sickness and Nagana in domestic animals and depends on the tsetse fly for dissemination. The complex T. brucei life cycle requires differentiation from the dividing long slender forms via the cell cycle arrested short stumpy forms (both in the mammalian bloodstream) to the procyclic forms of the insect vector. The signaling pathways that regulate differentiation are unknown but there is evidence for an involvement of cAMP. In search of the putative cAMP receptor, three catalytic and one regulatory PKA-like subunits have been previously cloned from T. brucei. The catalytic subunits possess all features of a classical PKA in terms of inhibitor and substrate specificity. It was shown that each of the catalytic PKAlike subunits binds to the regulatory subunit to form a dimeric PKA-like holoenzyme. Most surprisingly, we found that T. brucei PKA-like kinase, despite of its apparent similarities to a PKA, was not activated but instead inhibited by cAMP. Out of several other cyclic nucleotides that were tested on their effects on PKA-like kinase, only cGMP was able to activate the kinase, but in millimolar and thus most likely unphysiological concentrations. Assuming that the activation of PKA-like kinase might depend on its native, subcellular environment, an in vivo kinase assay was established in this work. It is based on the immunological detection of the phosphorylated form of the PKA reporter substrate VASP that was transgenically expressed in T. brucei. Interestingly, results from the in vivo assay did confirm the in vitro data, suggesting that T. brucei PKA-like kinase is in fact inhibited rather than activated by cAMP. Even though these findings challenge the original assumption that T. brucei PKA-like kinase transmits the differentation signal mimicked by cAMP antagonists, data from this work nevertheless provide evidence for an involvement of T. brucei PKA-like kinase in relaying extracellular cues. This is suggested from an increase in in vivo PKA activity in the presence of treatments that have either been shown to induce LS to SS differentiation (etazolate) or to participate in SS to PCF differentiation (cold shock, mild acid stress). In addition, in vivo PKA activity was stimulated with the PDE inhibitor dipyridamole and at hypoosmotic stress. In the context of a putative role for T. brucei PKA-like kinase in the regulation of differentiation, two of the catalytic isoforms (PKAC1 and PKAC2) were of particular interest. We found significant life cycle stage dependent differences in protein expression between the two almost identical isoforms. PKAC1 was nearly exclusively present in bloodstream forms and PKAC2 in procyclic cells. In addition, PKAC1, but not PKAC2 carries a phosphorylation that is restricted to the SS stage. This phosphorylation was mapped to the C-terminal threonine 324 by mass spectrometry. The functions of these life cycle stage dependent differences between PKAC1 and PKAC2 remain unknown. Reverse genetics did not reveal any functional differences between the isoforms, in fact, PKAC1 was even able to complement PKAC2 in procyclic PKAC2 knock-out cells. Results from several reverse genetic experiments indicate that T. brucei PKA-like kinase plays an important role in cell division. Depletion of either PKA-like subunit leads to a cytokinesis block. Depletion of the regulatory PKA-like subunit additionally results in altered basal body segregation. Given that 1) both cytokinesis and basal body movement had been previously suggested to be regulated by the trypanosomal flagellum (Kohl et al., 2003) and 2) the flagellum hosts T. brucei PKA-like kinase (C. Krumbholz, this lab) we propose that trypanosomal flagella act as signaling compartments for coordination of cell division.

Die Diagnostik der ausschließlich in Lateinamerika vorkommenden amerikanischen Trypanosomiasis (Chagaskrankheit) bereitet vor allem in den chronischen Infektionsstadien (Latenz, chronische Erkrankung) erhebliche Probleme, da in der Regel eine extrem niedrige Parasitämie vorliegt. Der in der akuten Phase bedeutsame Parasitennachweis gelingt in den Spätstadien häufig nicht, trotz Anwendung von Anreicherungsmethoden, Kultur und Xenodiagnose (Nachweis aus am Patienten angesetzten Überträgerwanzen). Zwar sind im chronischen Stadium nahezu regelmäßig spezifische Antikörper nachweisbar, die Aussagekraft der Immundiagnostik ist jedoch eingeschränkt. So bleibt die Immunantwort oft lebenslang positiv, auch wenn die Infektion spontan oder nach Chemotherapie ausgeheilt ist. Zudem gibt es falsch-positive Ergebnisse, z. B. aufgrund von Kreuzreaktionen mit Leishmanien und anderen Trypanosomen (z. B. Trypanosoma rangeli). Der sichere Nachweis einer Infektion in den Spätstadien ist jedoch von erheblicher Bedeutung. So kann durch eine rechtzeitige Therapie die Manifestation der meist intraktablen Spätstadien verhindert bzw. reduziert werden. Zudem wäre es bedeutsam chronische Infektionen bei seropositiven Frauen mit Kinderwunsch und bei Schwangeren zu erkennen, da auch asymptomatische Schwangere die Infektion auf das Kind übertragen können. Schließlich kommt in Hochendemiegebieten ein erheblicher Teil der Bevölkerung als Blutspender nicht in Frage, da alle Seropositiven ausgeschlossen werden, auch wenn offen bleibt ob tatsächlich eine chronische Infektion vorliegt. Zum Nachweis der extrem niedrigen Parasitämien im chronischen Stadium scheint die Polymerasekettenreaktion (PCR) besonders vielversprechend. Mittlerweile sind bereits mehrere PCR-Methoden zum Nachweis von Trypanosoma cruzi entwickelt und mit sehr unterschiedlichen Ergebnissen in der Diagnostik und Therapiekontrolle bei zahlenmäßig noch sehr begrenzten Patientenkollektiven eingesetzt worden. Die verschiedenen PCR-Protokolle beruhen auf dem Nachweis verschiedener Genabschnitte der nukleären DNA (nDNA) und der in hoher Kopienzahl vorliegenden Kinetoplasten-DNA (kDNA). Zudem wurden unterschiedliche Methoden zur Stabilisierung und Verarbeitung von Proben publiziert einschließlich solcher unter einfachen Feldbedingungen, wie sie in den Hauptverbreitungs-gebieten vorherrschen. Ziel dieser Arbeit war es die wichtigsten dieser PCR-Methoden unter experimentellen Bedingungen zu vergleichen und eine Methode zu identifizieren, die eine hohe Sensitivität und eine hohe Spezifität aufweist und robust funktioniert. Anschließend sollte eine Validierung mit Proben aus einem Endemiegebiet erfolgen. Ein weiteres Ziel war dabei, Methoden der Nukleinsäuren-Isolierung und -Konservierung unter Feldbedingungen zu untersuchen und zu optimieren. Im ersten Teil der Untersuchungen wurden 4 verschiedene PCR-Methoden optimiert und unter experimentellen Bedingungen hinsichtlich Sensitivität, Spezifität und Robustheit verglichen: (1) eine PCR mit den Primern TCZ1/TCZ2 zur Amplifikation eines konservierten nDNA- Abschnitts von 188 Basenpaaren (bp) einer repetitiven (ca. 700 Kopien/Zelle) Sequenz mit derzeit noch unklarer Funktion. (2) eine PCR mit den Primern BP1+BP2 zur Amplifikation eines hochkonservierten nDNA-Abschnitts von 692 bp des F29-Gens (Flagellin). (3) eine PCR mit den Primern 121/122 zur Amplifikation an zwei konstanten Regionen der kDNA, die eine variable kDNA-Region umschließen (330 bp). (4) eine nested PCR mit den Primerpaaren 121+89/90 und 91+122 zur Amplifikation eines 289 bp Abschnitts der kDNA (identische Teilregion der PCR-Methode Nr. 3) Die höchste Sensitivität für T. cruzi zeigte unter experimentellen Bedingungen die nested PCR (Methode Nr. 4) mit einem spezifischen Amplifikationsprodukt bis herab zu einer Konzentration von 0,001 Parasiten/µl (1 Parasit/ml). Die Spezifität der PCR-Protokolle TCZ1/2 (repetitive nDNA) und BP1/2 (F29-Flagellin) war hoch. Sie amplifizierten keine Genabschnitte von anderen Trypanosomatidae, mit Ausnahme eines deutlich differenten 615-620 bp-Amplifikats für T. rangeli beim BP1/2-Protokoll. Demgegenüber zeigten sowohl das 121/122-kDNA-Protokoll wie die kDNA-nested PCR nicht von T. cruzi differenzierbare Amplifikate mit T. rangeli und in der nested PCR auch mit T. brucei brucei, nicht jedoch bei verschiedenen Leishmania-Arten. Hinsichtlich ihrer Robustheit erwiesen sich die 4 PCR-Protokolle als unterschiedlich stabil und reproduzierbar. Das TCZ1/2-Protokoll war nicht stabil und ergab Amplifikate nur in einem sehr engen Toleranzbereich der Arbeitsbedingungen. Die anderen drei Methoden erwiesen sich als robust und zeigten im optimalen Arbeitsbereich stets reproduzierbare Ergebnisse. Weiterhin wurde 6M Guanidinhydrochlorid (G-HCl) als Zusatz für die Stabilisierung von Blutproben untersucht. Im Vergleich zu PBS wurde die Sensitivität der PCR-Protokolle mit G-HCl verbessert. Beim Vergleich verschiedener Methoden zur DNA-Isolation zeigte der QIAGEN Blood Mini Kit eine etwas höhere Sensitivität als die Phenol-Chloroform-Isoamyl-Methode. Im zweiten Teil der Untersuchungen wurden Blutproben von 44 Patienten mit anamnestisch diagnostizierter Chagaskrankheit in der Umgebung von Cochabamba, Bolivien, einem Hochendemiegebiet der Chagaskrankheit abgenommen. Diese wurden mit 6M Guanidinhydrochlorid stabilisiert und zur Untersuchung nach München gebracht. Die nested PCR zum Nachweis von kDNA erwies sich als sensitivste Methode zum Nachweis einer Parasitämie, bei 6 der 27 seropositiven Proben (22,2%) konnte ein T.cruzi-spezifisches Amplifikat nachgewiesen werden. Das 121/122-kDNA-Protokoll amplifizierte bei 4 der 27 Proben eine T.cruzi-spezifische Sequenz (14,8%). Mit Ausnahme eines Falles waren alle PCR-positiven Patienten bisher nicht therapiert worden. Mit den beiden nDNA-Protokollen (TCZ1/2- und BP1/2- Protokoll) ergab sich bei keiner dieser Proben ein Amplifikat. Bei den serologisch negativen oder grenzwertigen Patientenproben konnten mit keinem der 4 PCR-Protokolle ein Amplifikat nachgewiesen werden. Zudem wurden noch 30 Blutproben von gesunden Erwachsenen aus Deutschland untersucht. Hierbei zeigten sich ebenfalls keine Amplifikate bei den 4 Protokollen. Zusammengefaßt ergaben die Untersuchungen, daß die PCR-Protokolle zum Nachweis von kDNA am sensitivsten Trypanosoma cruzi im Blut nachweisen können; mit besonders hoher Sensitivität der nested PCR-Methode. Dies beruht wohl auf der hohen Kopienzahl der amplifizierten Zielsequenz in den kDNA-Minicircles (ca. 10.000 Kopien/Zelle) im Vergleich zu den untersuchten nDNA-Zielsequenzen. Allerdings werden von den kDNA-Protokollen auch andere Trypanosomen wie T. rangeli und T. brucei brucei (nur bei der nested PCR) miterfasst, im Gegensatz zu den hochkonservierten Zielsequenzen der untersuchten nDNA-Protokolle.

In der Einleitung wird die pathologische Anatomie und Physiologie der Speiseröhrenachalasie nach den bis heute vorliegenden Untersuchungsbefunden wiedergegeben. Der derzeitige Stand des histologischen Aufbaus der normalen Speiseröhrenwand wird beschrieben. Nach einer ausführlichen Darlegung der bereits in der Literatur vorhandenen mikroskopischen und submikroskopischen Untersuchungsergebnisse der Speiseröhrenwand bei der Achalasie wird an Hand von 6 eigenen Fällen pathohistologisch die Art der qualitativen und quantitativen Veränderungen des intramuralen Nervensystems der Speiseröhre insbesondere des Speiseröhrenabschnitts unterhalb der Dilatation in Verbindung mit den Veränderungen der übrigen Strukturelemente der Speiseröhrenwand in diesem Bereich geprüft und beschrieben. Diese Untersuchungen an Gewebsstücken aus dem Übergangsbereich Oesophagus - Magen führten zu folgendem Ergebnis: Die Mukosa aus dem Übergangsbereich Oesophagus - Magen eines Achalasiefalles bietet keinen Anhalt für ausgeprägte entzündliche Veränderungen. Die Längs- und Ringmuskelschicht der Tunica muscularis im Übergangsbereich Oesophagus - Magen weist in allen 6 Fällen eine deutliche Hypertrophie,leichte Dissoziation der Muskelfasern und Vermehrung des Bindegewebes zwischen denselben auf. In 2 von 6 Fällen finden sich kleine ovale bis runde Infiltrate polymorphkerniger Leukozyten in den Muskelfaser-bündeln. Bei einigen Fällen sind zwischen den Muskelfaser-bündelchen vereinzelt Erythrozyteninfiltrate zu beobachten. Im Stratum intermusculare der Tunica muscularis lassen sich teils oedematöse Dissoziation, teils Vermehrung des Bindegewebes oder Sklerose in allen Fällen nachweisen. 2 der 6 Fälle zeigen um die Gefässe sowie diffus im Bindegewebe verstreut Ansammlungen polymorphkerniger Leukozyten. In einem Teil der Fälle sieht man eine vermehrte Vascularisation des intermuskulären Bindegewebes und Verdickung der Gefäßwände. Gelegentlich kann man auch Erythrozyteninfiltrate nachweisen, die wie jene im Bereich der Tunica muscularis sicher bei der Praeparatexcision entstanden sind. In einigen Fällen sind vereinzelt leicht gequollene Achsenyzlinderbruchstuecke eingestreut. Umgeben von diesen Bindegewebsverhältnissen besteht bei den meisten Ganglionanschnitten mehr oder weniger deutliche Kern- bzw. Zellzunahme pro Flächeneinheit, die zum größten Teil auf das Auftreten und die Dichte von Zellen mit spindelförmigen, längsovalen, runden und polymorphen Kernanschnitten und zum geringsten Teil auf Rundzellinfiltrate zurückzuführen ist. Die Zunahme der Zellen mit spindelförmigen, längsovalen, runden und polymorphen Kernen pro Flächeneinheit der im Schnitt getroffenen Ganglien trägt proliferativen Charakter. Die Ganglionanschnitte zeigen teilweise das Bild der Vernarbung, in einigen Fällen das Bild der Dissoziation. Nur ein Teil der im Schnitt getroffenen Ganglien enthält Ganglienzellen,sie können sogar vollkommen fehlen. Auch in Bezug auf den ganglienzellhaltigen Ganglionanschnitt lässt sich eine Verminderung in der Anzahl der Ganglienzellen feststellen. Die Ganglienzellen zeigen teils normales Aussehen, teils pathologische Veränderungen im Sinne feinkörniger oder grobkörniger Zellschwellung mit ganz vereinzelter Hauptdendritenschwellung oder im Sinne einer Kolliquationsnekrose. Ferner lassen sich an den Stellen zugrunde gegangener Nervenzellen Hüllzellknötchen nachweisen. Gelegentlich findet man in den Ganglionanschnitten neuromartige Proliferation praeganglionärer Nervenfasern. In den Anschnitten primärer extraganglionärer Faserstränge treten vorwiegend Zellen mit spindelförmigen und polymorphen Kernen auf. Bei einzelnen primären Faserbündeln kann man eine Dissoziation oder Schwellung derselben beobachten. In einzelnen Fällen besteht körniger oder vakuoliger Zerfall der in die Remak'schen Fasern eingeschmiegten Achsenzylinder. Bei einem Fall last sich eine Infiltration polymorphkerniger Leukozyten innerhalb des Anschnitts eines primären Faserstrangs nachweisen. Ferner wird an 4 Kaninchen experimentell die Frage geprüft, ob durch die therapeutische Dehnung der unteren Speiseröhre und der Kardia Zerreißungen der Muskelwand und damit Veränderungen an ihren nervösen Elementen entstehen können, welche möglicherweise das histologische Untersuchungsergebnis beeinflussen. Dabeihaben die histologischen Untersuchungen der Praeparate aus dem untersten Oesophagus und dem Übergangsbereich Oesophagus - Magen vor und nach der Dehnungsbehandlung bei Kaninchen folgendes ergeben; Das durch experimentelle Dehnung erzeugte histologische Bild gleicht doch in keinem Fall den pathohistologischen Befunden von nicht gedehnten Frühfällen der Achalasie und von Achalasiefällen bei denen das Praeparat erst nach Dehnungsbehandlung bei einer später durchgeführten Operation entnommen wurde. Es ist daher anzunehmen, dass eine vorausgegangene therapeutische Dehnung des untersten Oesophagus und des Übergangsbereichs Oesophagus - Magenbei der Achalasie das pathohistologische Geschehen nur geringfügig beeinflussen wird. Aus den in der Literatur vorliegenden und eigenen histologischen Befunden,die in den einzelnen Wandschichten und Wandabschnitten der an Achalasie erkrankten Speiseröhre erhoben worden sind, lässt sich das folgende pathohistologische Gesamtbild ableiten: In der Tunica mucosa, Tunica submucosa, Tunica muscularis und besonders im Stratum intermusculare sind bei der Achalasie von den ersten Krankheitstagen an entzündliche Prozesse nachzuweisen, denen Veränderungen und Zerstörungen einzelner Gewebselemente folgen. Es werden einerseits das Muskelgewebe und das interstitielle Bindegewebe, andererseits die Nervenstrukturen der Oesophaguswand betroffen. Als Endzustand findet man eine ausgesprochene Sklerose oder wenigstens eine Vermehrung des Bindegewebes in der Submukosa, zwischen den Muskelbündeln, den einzelnen Muskelzellen und im Stratum intermusculare. Ferner wird Hypertrophie, Atrophie, hyaline Degeneration, Nekrose oder Verkalkung der Muskelfasern beobachtet. Im submikroskopischen Bild bestehen nur mehr restliche Kontakte zwischen den einzelnen glatten Muskelzellen durch Protoplasmabrücken und Membrankontakte. Zudem kommt es zu ausgedehnter Vakuolisierung des Zytoplasmas glatter Muskelzellen. Im Bereich der Ganglien kommt es zu degenerativen Veränderungen an den Ganglienzellen (Zellschwellung, Hauptdendriten-schwellung, Kolliquationsnekrose), wobei die Veränderungen bis zum restlosen Ausfall der Ganglienzellen (Hüllzellknötchenbildung) reichen können. Eine Neuropilemstruktur ist in letzterem Falle innerhalb des Ganglion nicht mehr nachweisbar. Sie wird durch Narbengewebe in Form von proliferierenden Zellen mit spindelförmigen, ovalen,runden und polymorphen Kernen ersetzt. Vereinzelt kann man in den Ganglien neuromartige Proliferation präganglionärer Nervenfasern erkennen. Die primären extraganglionären Faserstränge zeigen gelegentlich Dissoziation oder Schwellung und in einzelnen Fällen körnigen und vakuoligen Zerfall der Nervenfasern. Für die Megaoesophagusfälle im Rahmen der Chagaskrankheit kann die Ätiologie der pathohistologischen Veränderungen als geklärt gelten. Die entzündlichen Prozesse und die Plexuszerstörung im Bereich der ganzen Speiseröhrenwand lassen sich bei der Chagaskrankheit auf das Neurotoxin bzw. die toxischen Zerfallsprodukte des Trypanosoma cruzi zurückführen. Bei den Megaoesophagus- bzw. Achalasiefällen, die nicht mit einer Chagaserkrankung in Verbindung gebracht werden können und bei denen noch keine Toxine anderer Krankheitserreger oder andere Ursachen für die pathohistologischen Veränder-ungen des Plexus und anderer Elemente der Speiseröhrenwand ermittelt wurden, bleibt die Erstursache weiterhin unbekannt.