Podcasts about Protease

Amino acids are the true building blocks of the human body. This episode of Vitality Radio focuses specifically on Lysine, Tyrosine, and Acetyl-L-Carnitine. Jared unpacks the unique impact of these powerful aminos and why they deserve a closer look. You'll learn about their impressive benefits as individual nutrients - immunity, brain boosting, energy, thyroid health, and more! Jared also explains how single amino acids work vs. protein as a whole, and additionally, the role of digestive enzymes in breaking down protein to ensure we absorb these vital amino acids. Products:Lysine, Tyrosine, and Acetyl-L-Carnitine Additional Information:#479: Amino Acid Spotlight: Glycine, Citrulline, and Glutamine#412: A Natural Approach to Supporting Your Body Through ShinglesVisit the podcast website here: VitalityRadio.comYou can follow @vitalitynutritionbountiful and @vitalityradio on Instagram, or Vitality Radio and Vitality Nutrition on Facebook. Join us also in the Vitality Radio Podcast Listener Community on Facebook. Shop the products that Jared mentions at vitalitynutrition.com. Let us know your thoughts about this episode using the hashtag #vitalityradio and please rate and review us on Apple Podcasts. Thank you!Just a reminder that this podcast is for educational purposes only. The FDA has not evaluated the podcast. The information is not intended to diagnose, treat, cure, or prevent any disease. The advice given is not intended to replace the advice of your medical professional.

TWiV reveals a novel H5N1 reassortant virus in Cambodia, circulating vaccine derived poliovirus type 2 in more countries, circulation in the blood of humans of infectious parvovirus B19 coated with active proteases, and B cell receptor dependent enhancement of dengue virus infection. Hosts: Vincent Racaniello, Dickson Despommier, Kathy Spindler, and Brianne Barker Subscribe (free): Apple Podcasts, RSS, email Become a patron of TWiV! Links for this episode MicrobeTV Discord Server MicrobeTV Fundraiser Novel H5N1 in Cambodia (medRxiv) More cVDVP2 circulation (polioeradication.org) Infectious parvovirus B19 with proteases (Nat Comm) B cell receptor enhancement of dengue disease (PLoS Path) Timestamps by Jolene. Thanks! Weekly Picks Brianne – See How Many Lives Vaccines Have Saved Around the World based on Lancet study Dickson – 2024 Wildlife Photographer of the Year Kathy – 450 Million year old arthropods preserved in fool's gold. Primary article Pyrite video Vincent – ‘We need to be ready for a new world': scientists globally react to Trump election win Listener Picks Jack – Coronavirus vaccine update Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv Content in this podcast should not be construed as medical advice.

Did you know there is an enzyme that can help you break down abnormal cells and proteins in the body like cysts, scar tissue, and blood clots, as well as detoxifying your blood at a cellular level? On this episode of Vitality Radio, Jared interviews our favorite enzyme educator, Julia Craven, VP of Education for Enzymedica. They do a deep dive on all of the amazing things Nattokinase can do in the body. You'll learn how it works and why it can replace baby aspirin for cardiovascular health and so many other amazing functions in the body. Wondering if it's something you should add to your regimen? Listen and decide if it's best for you!Products:Enzymedica Natto-KEnzymedica Enzyme DefenseSource Natural NattoAdditional Information:#383: The Incredible Benefits of Enzymes For Digestion, Immunity, and Overall Health With Julia Craven#301: Systemic Enzymes for Mucus, Candida, Immune Support, Heart Health and more. Also a Brand New Magnesium! Guest, Julia Craven#292: Food Sensitivities and Digestive Enzymes. How to Ease The Burden with Julia CravenVisit the podcast website here: VitalityRadio.comYou can follow @vitalityradio and @vitalitynutritionbountiful on Instagram, or Vitality Radio and Vitality Nutrition on Facebook. Join us also in the Vitality Radio Podcast Listener Community on Facebook. Shop the products that Jared mentions at vitalitynutrition.com. Let us know your thoughts about this episode using the hashtag #vitalityradio and please rate and review us on Apple Podcasts. Thank you!Please also join us on the Dearly Discarded Podcast with Jared St. Clair.Just a reminder that this podcast is for educational purposes only. The FDA has not evaluated the podcast. The information is not intended to diagnose, treat, cure, or prevent any disease. The advice given is not intended to replace the advice of your medical professional.

References PLoS Biol 2014. 12(10): e1001969 J Biol Chem. 2012 May18;287(21):17589-17597 J Biol Chem. 2012 Nov 23;287(48):40131-9 Nature 2019. volume 575, pages 361–365 Alleluia: Lobet den Herren. --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

References Cell Death & Disease 2022. volume 13.Article number: 444. Nature 2019. volume 575, pages 361–365 Scientific Reports 2021. volume 11, Article number: 16512 Experimental & Molecular Medicine 2020. volume 52, pages 1496–1516 Mozart, WA. 1788. Piano Trio in G Major, KV 564 https://youtu.be/oOEuVtr8sF0?si=3-9RK1XkGkSWne7I --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

In this episode, we review the high-yield topic of⁠ Protease Inhibitors⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠from the Microbiology section. Follow ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Medbullets⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets --- Send in a voice message: https://podcasters.spotify.com/pod/show/medbulletsstep1/message

Julia Craven from Enzymedica is back on Vitality Radio this week to talk with Jared all about the incredible benefits of enzymes. They'll cover how digestive enzymes benefit the body above and beyond digestion. You'll also learn how to use systemic enzymes to partner with your body's natural immune function, and how safe they are for just about anyone. Also discussed are some pro tips for maintaining health through the hectic and indulgent holiday season. As always, Julia is a wealth of knowledge on the subject of enzymes and will leave you wanting to learn more!Products:Enzymedica ProductsVital 5 Assimil-8 Digestive EnzymesBerberineAdditional Information:#301: Systemic Enzymes for Mucus, Candida, Immune Support, Heart Health and more. Also a Brand New Magnesium! Guest, Julia Craven#292: Food Sensitivities and Digestive Enzymes. How to Ease The Burden with Julia Craven#227: VR Vintage: There is an Herbal Supplement that Works for Diabetes, Blood Pressure and Cholesterol Better than Drugs! Berberine is that Powerful!Visit the podcast website here: VitalityRadio.comYou can follow @vitalityradio and @vitalitynutritionbountiful on Instagram, or Vitality Radio and Vitality Nutrition on Facebook. Join us also in the Vitality Radio Podcast Listener Community on Facebook. Shop the products that Jared mentions at vitalitynutrition.com. Let us know your thoughts about this episode using the hashtag #vitalityradio and please rate and review us on Apple Podcasts. Thank you!Please also join us on the Dearly Discarded Podcast with Jared St. Clair.Just a reminder that this podcast is for educational purposes only. The FDA has not evaluated the podcast. The information is not intended to diagnose, treat, cure, or prevent any disease. The advice given is not intended to replace the advice of your medical professional.

References J Pharm Bioallied Sci. 2019 May; 11(Suppl 2): S135–S139. J Oral Microbiol. 2017; 9(1): 1400858. J Dent Res. 2020 Jun;99(6):644-649. Mozart WA 1782. D major, K. 385. Symphony 35 (Haffner) --- Send in a voice message: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/message Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

We are at the end of the road of our anti-platelet pathway exploration!!!! We look at 2 different ways of inhibiting the platelets from forming a clot and the different patient populations that these drugs are used. Hooray to the anti-platelets though I'm sure this isn't the end there must be another novel/cutting edge therapy just around the corner that a scientist/discoverer is just about to unveil...... --- Support this podcast: https://podcasters.spotify.com/pod/show/wambui-wamburu/support

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.01.530659v1?rss=1 Authors: Anticevic, I., Otten, C., Vinkovic, L., Jukic, L., Popovic, M. Abstract: DNA-protein crosslinks (DPCs) are very frequent and damaging DNA lesions that affect all DNA transactions, which in turn can lead to the formation of DSBs, genomic instability and cell death. At the organismal level, impaired DPC repair (DPCR) is associated with cancer, aging, and neurodegenerative phenotypes. Despite the severe consequences of DPCs, the mechanisms of the DPCR pathway at the organism level are still largely unknown. SPRTN is a protease that removes most cellular DPCs during replication, whereas tyrosyl-DNA phosphodiesterase 1 repairs one of the most abundant enzymatic DPCs, topoisomerase 1-DPC (TOP1-DPC). How these two enzymes repair DPCs at the organism level is currently unknown. Using the zebrafish animal model and human cells, we demonstrate that TDP1 and SPRTN repair endogenous, camptothecin- and formaldehyde-induced DPCs, including histone H3- and TOP1-DPCs. We show that resolution of H3-DNA crosslinks depends on upstream proteolysis by SPRTN and subsequent peptide removal by TDP1 in RPE1 cells and zebrafish embryos, whereas SPRTN and TDP1 function in different pathways in the repair of endogenous TOP1-DPCs. 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/2023.02.26.530105v1?rss=1 Authors: Bi, P. Y., Killackey, S. A., Schweizer, L., Arnoult, D., Philpott, D. J., Girardin, S. E. Abstract: Mitochondrial stress inducers, such as the proton ionophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and the ATPase pump inhibitor oligomycin, trigger the DELE1-HRI branch of the integrated stress response (ISR) pathway. Previous studies performed using epitope-tagged forms of DELE1 showed that these stresses induced the accumulation of a cleaved form of DELE1, DELE1-S, which stimulates HRI. Here, we report that mitochondrial protein import stress (MPIS) is an overarching stress that triggers the DELE1-HRI pathway, and that endogenous DELE1 could be cleaved into two forms, DELE1-S and DELE1-VS, the latter accumulating only upon non-depolarizing MPIS. We further showed that DELE1 specifically senses MPIS triggered by the inhibition of the TIM23 complex at the inner mitochondrial membrane (IMM). While MPIS can also cause mitophagy induction through engagement of the NLRX1-RRBP1 pathway, we observed that DELE1-HRI and NLRX1-RRBP1 signaling were engaged independently upon MPIS. Surprisingly, our results suggest that in our cellular model the mitochondrial protease OMA1 was dispensable for DELE1 cleavage upon MPIS. Instead, we identified a key role for another mitochondrial protease, HtrA2, in mediating the cleavage of DELE1 into DELE1-S and DELE1-VS. Our data further suggest that DELE1 is likely cleaved into DELE1-S by HtrA2 in the cytosol, while the DELE1-VS form might be generated during halted translocation of the protein into mitochondria. Together, this study identifies MPIS as the overarching stress detected by DELE1 and identifies HtrA2 as a critical protease involved in DELE1 processing. 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/2023.02.12.528175v1?rss=1 Authors: Kume, M., Ahmad, A., DeFea, K. A., Vagner, J., Dussor, G., Boitano, S., Price, T. J. Abstract: Background and Purpose: Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common, dose-limiting side effect of cancer therapy. Protease-activated receptor 2 (PAR2) is implicated in a variety of pathologies, including CIPN. In this study, we demonstrate the role of PAR2 expressed in sensory neurons in a paclitaxel (PTX)-induced model of CIPN in mice. Experimental Approach: CIPN was induced in both PAR2 knockout/WT mice and mice with PAR2 ablated in sensory neurons via the intraperitoneal injection of paclitaxel. In vivo behavioral studies were done in mice using von Frey filaments and the Mouse Grimace Scale. We then examined immunohistochemical staining of dorsal root ganglion (DRG) and hind paw skin samples from CIPN mice to measure satellite cell gliosis and intra-epidermal nerve fiber (IENF) density. Pharmacological reversal of CIPN pain was tested with the PAR2 antagonist C781 Key Results: Mechanical allodynia caused by paclitaxel treatment was alleviated in PAR2 knockout mice of both sexes. In the PAR2 sensory neuronal conditional knockout (cKO) mice, both mechanical allodynia and facial grimacing were attenuated in mice of both sexes. In the dorsal root ganglion of the paclitaxel-treated PAR2 cKO mice, satellite glial cell activation was reduced compared to control mice. IENF density analysis of the skin showed that the paclitaxel-treated control mice have a reduction in nerve fiber density while the PAR2 cKO mice had a comparable skin innervation as the vehicle-treated animals. Similar results were seen with satellite cell gliosis in the DRG where gliosis induced by PTX was absent in PAR cKO mice. Finally, C781 was able to transiently reverse established PTX-evoked mechanical allodynia. Conclusions and Implications: Our work demonstrates that PAR2 expressed in sensory neurons plays a key role in paclitaxel-induced mechanical allodynia, spontaneous pain and signs of neuropathy, suggesting PAR2 as a possible therapeutic target in multiple aspects of paclitaxel CIPN. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

References Peptides . 2020 Jan;123:170177 Molecular Cancer. 2020. volume 19, Article number: 39. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.23.525269v1?rss=1 Authors: Sharafeddin, F., Ghaly, M., Simon, T. B., Ontiveros-Angel, P., Figueroa, J. D. Abstract: Childhood traumatic stress profoundly affects prefrontal cortical networks regulating top-down control of eating and body weight. However, the neurobiological mechanisms contributing to trauma-induced aberrant eating behaviors remain largely unknown. Traumatic stress influences brain immune responses, which may, in turn, disrupt prefrontal cortical networks and behaviors. The tumor necrosis factor alpha-converting enzyme / a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and neuroinflammation. This study aimed to determine the role of TACE/ADAM17 on traumatic stress-induced disruption of eating patterns. We demonstrate a novel mechanistic connection between prefrontal cortical TACE/ADAM17 and trauma-induced eating behaviors. Fifty-two (52) adolescent Lewis rats (postnatal day, PND, 15) were injected intracerebrally either with a novel Accell SMARTpool ADAM17 siRNA or a corresponding siRNA vehicle. The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Observation cages were used to monitor ethological behaviors in a more naturalistic environment over long periods. We found that traumatic stress blunts startle reactivity and alter eating behaviors (increased intake and disrupted eating patterns). We also found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited decreased eating and increased grooming behaviors compared to controls. These changes were associated with decreased AIF-1 expression (a typical marker of microglia and neuroinflammation). This study demonstrates that prefrontal cortical TACE/ADAM17 is involved in neuroinflammation and may play essential roles in regulating feeding patterns under stress conditions. TACE/ADAM17 represents a promising target to ameliorate inflammation-induced brain and behavior alterations. 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/2023.01.22.525054v1?rss=1 Authors: Kliszczak, M., Moralli, D., Jankowska, J., Bryjka, P., Subha, L., Goncalves, T., Hester, S., Fischer, R., Clynes, D., Green, C. M. Abstract: Hereditary fibrosing poikiloderma (HFP) is a rare human dominant negative disorder caused by mutations in the FAM111B gene that encodes a nuclear trypsin-like serine protease. HFP patients present with symptoms including skin abnormalities, tendon contractures, myopathy and lung fibrosis. We characterised the cellular roles of human FAM111B using U2OS and MCF7 cell lines and report here that the protease interacts with components of the nuclear pore complex. Loss of FAM111B expression resulted in abnormal nuclear shape and reduced telomeric DNA content suggesting that FAM111B protease is required for normal telomere length; we show that this function is independent of telomerase or recombination driven telomere extension. Even though FAM111B-deficient cells were proficient in DNA repair, they showed hallmarks of genomic instability such as increased levels of micronuclei and ultra-fine DNA bridges. Interestingly, FAM111B variants, including mutations that cause HFP, showed more frequent localisation to the nuclear lamina suggesting that accumulation of mutant FAM111B at the nuclear periphery may drive the disease pathology. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Dr. Tram Tran, the Chief Medical Officer at Glympse Bio, is taking the knowledge about the mechanistic roles protease play in many diseases to develop an injectable biosensor to measure protease activity rather than just a one-time measurement of the amount of protein in the blood. The platform uses machine learning to analyze different protease levels and the protease activity over time to come up with a classifier and differentiate between disease activity and not disease activity. Tram explains, "So, a couple of years ago, though, I think recognizing that having an injectable platform and then having the patient urinate and check the urine for the level of protease activity might be a little bit more complicated than what would be ideal in the clinic for the patient. We actually were able to switch over to a blood-based test, where we are able to measure the patient's disease activity via protease activity via a simple blood test. And so, I think that was really a remarkable change over the past couple of years." "We've been working on a couple of different diseases and better understanding how to measure and understand diseases and protease activity through a simple blood test now. So, I think that's really important. This ex vivo platform development was a key change. We presented data last year on NASH, which is a very common disease, non-alcoholic steatohepatitis. And this year, we're talking more about liver cancer or hepatocellular carcinoma." @GlympseBio #Diagnostic #Biosensor #LiverDisease #HCC #HepatocellularCarcinoma #ProteinActivity #Protease GlympseBio.com Download the transcript here

Dr. Tram Tran, the Chief Medical Officer at Glympse Bio, is taking the knowledge about the mechanistic roles protease play in many diseases to develop an injectable biosensor to measure protease activity rather than just a one-time measurement of the amount of protein in the blood. The platform uses machine learning to analyze different protease levels and the protease activity over time to come up with a classifier and differentiate between disease activity and not disease activity. Tram explains, "So, a couple of years ago, though, I think recognizing that having an injectable platform and then having the patient urinate and check the urine for the level of protease activity might be a little bit more complicated than what would be ideal in the clinic for the patient. We actually were able to switch over to a blood-based test, where we are able to measure the patient's disease activity via protease activity via a simple blood test. And so, I think that was really a remarkable change over the past couple of years." "We've been working on a couple of different diseases and better understanding how to measure and understand diseases and protease activity through a simple blood test now. So, I think that's really important. This ex vivo platform development was a key change. We presented data last year on NASH, which is a very common disease, non-alcoholic steatohepatitis. And this year, we're talking more about liver cancer or hepatocellular carcinoma." @GlympseBio #Diagnostic #Biosensor #LiverDisease #HCC #HepatocellularCarcinoma #ProteinActivity #Protease GlympseBio.com Listen to the podcast here

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.13.520278v1?rss=1 Authors: Hu, M., Bai, Y., Zheng, X., Zheng, Y. Abstract: Many corals form a mutually beneficial relationship with the dinoflagellate algae called Symbiodiniaceae. Cells in the coral gastrodermis recognize, phagocytose, and house the algae in an organelle called symbiosome, which supports algae photosynthesis and nutrient exchange with corals. Rising ocean temperature disrupts this endosymbiotic relationship, leading to alga loss, coral bleaching and death, and the degradation of marine ecosystems. Mitigation of coral death requires a mechanistic understanding of coral-algal endosymbiosis. We have developed genomic resources to enable the use of a soft coral Xenia species (sp.) as a model to study coral-algal endosymbiosis. Here we report an effective RNA interference (RNAi) method and its application in the functional studies of genes involved in early steps of endosymbiosis. We show that an endosymbiotic cell marker called LePin (for its Lectin and kazal Protease inhibitor domains) is a secreted host lectin that binds to algae to initiate the formation of alga-containing endosymbiotic cells. The evolutionary conservation of LePin among marine endosymbiotic anthozoans suggests a general role in coral-algal recognition. Coupling bioinformatics analyses with RNAi and single cell (sc)-RNA-seq, we uncover three gene expression programs (GEP) influenced by LePin during the early and middle stages of endosymbiotic lineage development. Further studies of genes in these GEPs lead to the identification of two scavenger receptors that support the formation of alga-containing host endosymbiotic cells, most likely by initiating phagocytosis and modulating coral immune response. We also identify two host actin regulators for endosymbiosis, which shed light on the phagocytic machinery and a possible mechanism for symbiosome formation. Our findings should usher in an era of mechanistic studies of coral-algal endosymbiosis. 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/2022.12.08.519463v1?rss=1 Authors: Vangansewinkel, T., Lemmens, S., Tiane, A., Geurts, N., Dooley, D., Vanmierlo, T., Pejler, G., Hendrix, S. Abstract: Traumatic spinal cord injury (SCI) most often leads to permanent paralysis due to the inability of axons to regenerate in the adult mammalian central nervous system (CNS). In the past, we have shown that mast cells (MCs) improve the functional outcome after SCI by suppressing scar tissue formation at the lesion site via mouse mast cell protease 6 (mMCP6). In this study, we investigated whether recombinant mMCP6 can be used therapeutically to improve the functional outcome after SCI. Therefore, we applied mMCP6 locally via an intrathecal catheter in the subacute phase after a spinal cord hemisection injury in mice. Our findings showed that hind limb motor function was significantly improved in mice that received recombinant mMCP6 compared to the vehicle-treated group. In contrast to our previous findings in mMCP6 knockout mice, the lesion size and expression levels of the scar components fibronectin, laminin, and axon growth-inhibitory chondroitin sulfate proteoglycans were not affected by the treatment with recombinant mMCP6. Surprisingly, no difference in infiltration of CD4+ T cells and reactivity of Iba-1+ microglia/macrophages at the lesion site was observed between the mMCP6 treated mice and control mice. Additionally, local protein levels of the pro- and anti inflammatory mediators IL-1{beta}, IL-2, IL-4, IL-6, IL 10, TNF-, IFN{gamma}, and MCP-1 were comparable between the two treatment groups, indicating that locally applied mMCP6 did not affect inflammatory processes after injury. However, the increase in locomotor performance in mMCP6-treated mice was accompanied by reduced demyelination and astrogliosis in the perilesional area after SCI. Consistently, we found that TNF-a/IL-1B-astrocyte activation was decreased, and that oligodendrocyte precursor cell (OPC) differentiation was increased after recombinant mMCP6 treatment in vitro. Mechanistically, this suggests effects of mMCP6 on reducing astrogliosis and improving (re)myelination in the spinal cord after injury. In conclusion, these data show for the first time that recombinant mMCP6 is therapeutically active in enhancing recovery after SCI. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

When upperclassman Skye Fitzgerald visits their lab to ask for help with a research project, they are not expecting her to be so intriguing. Afterall, she's just a average girl with an average life. But, when they start to get to know her better, they realize she may have more in common with them than they thought.

Artem's Instagram:https://instagram.com/skincaresarai?igshid=YmMyMTA2M2Y=Watch on YouTube - https://youtu.be/BQwog80ThWQAbib Heartleaf Sun Calming Essence Drop SPF 50 at yesstyle:https://ystyle.co/12JPUse Rewards Code NOBSBEAUTY for an additional discount! Full Ingredients List:Water, Dibutyl Adipate, Houttuynia Cordata Extract, Alcohol, Caprylyl Methicone, Diethylamino Hydroxybenzoyl Hexyl Benzoate, Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine, Phenethyl Benzoate, Polymethylsilsesquioxane, Polysilicone-15, Methylene Bis-Benzotriazolyl Tetramethylbutylphenol, Ethylhexyl Triazone, Hexyl Laurate, Niacinamide, Polyglyceryl-6 Stearate, Diethylhexyl Butamido Triazone, Aspergillus Ferment, Triticum Aestivum (Wheat) Seed Extract, 1,2-Hexanediol, Pentylene Glycol, C20-22 Alkyl Phosphate, Panthenol, Decyl Glucoside, Hydroxyacetophenone, Tromethamine, Ethylhexyl Olivate, Polyglyceryl-6 Behenate, Sodium Acrylates Copolymer, Polyglyceryl-4 Oleate, Dipotassium Glycyrrhizate, Adenosine, Glycerin, Sodium Phytate, Maltodextrin, Lipase, Protease, C20-22 Alcohols, Xanthan Gum******My second channel, for random things that don't fit here. https://www.youtube.com/channel/UCZwJQwh2qHT9qUrseCNasHg*******Podcast LinksApple - https://b.link/No_BS_Apple_PodcastGoogle - https://b.link/No_BS_Google_PodcastAmazon - https://b.link/No_BS_Amazon_PodcastSpotify - https://b.link/No_BS_Spotify_PodcastRSS - https://feeds.redcircle.com/671dd1b2-a989-41d5-94d5-30c014e06149********Sephora - https://fxo.co/1231867/sephoraUlta - https://fxo.co/1231867/ultaGeek and Gorgeous - https://iaff.geekandgorgeous.com/idevaffiliate.php?id=169&url=131 Amazon - https://www.amazon.com/shop/nobsbeautyYes Style - https://ys.style/kk2Vjrv798Style Korean - http://www.stylekorean.com/?af_id2=nobsbeautyDrmtlgy - https://www.drmtlgy.com/?ref=nobsbeautyThese are affiliate links if you purchase anything from one of these stores using this link No BS Beauty will make a small commission on what you buy.********www.noBSbeauty.com*******My Patreon - https://www.patreon.com/noBSbeauty*******PayPal Tip Jar - https://bit.ly/donate_NBSBIf you want to leave a tip ... Thanks! *****

Rohit Prasad, a metallurgist at the University of Utah, is on the show to talk about hemimorphite. This somewhat obscure mineral contains a type of metal that is relatively new to the world economy and Rohit has some interesting insights to share about it. In addition, he plays a little bit of beer pong and explains why he sometimes sweet-talks his opponents. Finally, Marquis talks about Protease and Gentiles, two of his upcoming books.

These group of drugs still going strong!! First one approved in 1995. Yet another enzyme being inhibited to get this virus under control (read suppressed). Listen up!

Thank you for joining us for our 2nd Cabral HouseCall of the weekend! I'm looking forward to sharing with you some of our community's questions that have come in over the past few weeks… Bryan: Hi Dr Cabral. Just want to start by thanking you for everything you do for me and so many people. You (and Julia) have helped me uncover a couple of root causes to some of my dis-eases and I'm feeling much better overall. I travel quite a bit for work, sometimes have to stay in hotels, and just find myself in situations where I can't really cook and it might take a lot of effort to find something healthy. I always take my DNS powder and shaker bottle with me everywhere for the morning and sometimes afternoon shake. Do you have any recommendations for eating clean lunches and dinners while on the road or somewhere where it's difficult to cook? Thank you so much.   Anonymous: Dr. Cabral, I recently ran the heavy metals and minerals test and it was recommended that I start on a multi vitamin for some subtle mineral deficiencies. I am using the equilife multi and have noticed my urine taking on a neon yellow color. I am well hydrated, and my urine very rarely goes past a very pale yellow, mostly clear. Is this a sign that there are vitamins that are not being absorbed or possibly that I am getting too much of certain vitamins and simply offloading the excess? Thanks for all you do!   Lesley: Hi Last year I was admitted to hospital with Covid pneumonitis and had oxygen for 12 days. I was hypoxic on admission but not noticeably breathless(silent hypoxia). I have been on a good nutrition plan since hospital discharge and taking zinc, vit c and vit d. I have just had a 12 week follow up X-ray which shows resolving Covid pneumonitis. I feel quite well but worried about the recovery of my lungs. My blood saturation is good 99%. Please can you give me any advice on what I can do to improve my lung recovery. Many thanks   Diana: Hi Dr. Cabral, thank you for everything you do and your daily podcasts! I have a question about digestive enzymes. Is there such a thing as being allergic to digestive enzymes? My son has Alopecia Areata, never had any stomach issues like bloating and vomiting, but he does when he takes digestive enzymes, he has tried 3 different and they all had the following enzymes in comment: Protease, amylase, lipase. Any idea of what could be the reason for bloating and vomiting after taking digestive enzymes? It also triggered a flareup. I want to do the CBO protocol, but I am afraid of him losing more hair because of the biofilm distributor and die off symptoms. He is 15 years old and it's been very hard.   Michelle: I have a family member who was just diagnosed with mitochondrial disease? Can you recommend an ayurvedic/ functional medicine approach?Labs or tests that she should have run? Any insights would be appreciated--love your podcast!   Lorena: We all know how estrogen dominance and weight gain in the mid section are related. But this is interesting because there have been studies (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460681/) that show how the risk of diabetes was reduced by 62% in women currently using HRT (hormone replacement therapy with estradiol included) compared to women who had never had HRT. One resource suggested that loss of estradiol, the primary human estrogen, from either natural or surgical menopause causes an abrupt reduction in metabolic rate, a tendency to increased fat around the middle, increased problems with cholesterol and triglycerides, and increased progression to metabolic syndrome. So which one is it? Does it cause weight gain or not? I'm confused now and I only trust your advice haha… Thank you for tuning into this weekend's Cabral HouseCalls and be sure to check back tomorrow for our Mindset & Motivation Monday show to get your week started off right! - - - Show Notes & Resources:  http://StephenCabral.com/2263 - - - Dr. Cabral's New Book, The Rain Barrel Effect https://amzn.to/2H0W7Ge - - - Join the Community & Get Your Questions Answered: http://CabralSupportGroup.com - - -  Dr. Cabral's Most Popular At-Home Lab Tests: > Complete Minerals & Metals Test (Test for mineral imbalances & heavy metal toxicity) - - - > Complete Candida, Metabolic & Vitamins Test (Test for 75 biomarkers including yeast & bacterial gut overgrowth, as well as vitamin levels) - - - > Complete Stress, Mood & Metabolism Test (Discover your complete thyroid, adrenal, hormone, vitamin D & insulin levels) - - - > Complete Stress, Sleep & Hormones Test (Run your adrenal & hormone levels) - - - > Complete Food Sensitivity Test (Find out your hidden food sensitivities) - - - > Complete Omega-3 & Inflammation Test (Discover your levels of inflammation related to your omega-6 to omega-3 levels)

Todos Medical Ltd CEO Gerald Commissiong tells Proactive its majority-owned subsidiary 3CL Pharma Ltd announced that its mechanism-based 3CL protease inhibitors Tollovir and Tollovidthat target the active site of the 3CL protease -- showing robust inhibitory activity against the 3CL protease of the BA.1 and BA.2 strains of the Omicron SARS-CoV-2 variant of concern (VOC). Additionally, the company said Tollovir and Tollovid showed inhibitory activity against the original wild-type SARS-CoV-2 strain, as well as the Alpha, Beta, Delta, and Gamma VOCs.

Welcome to 2022 family. In this short episode I will explain what gut enzymes are & how they relate to metabolic flexibility. Enjoy & let's crush 2022!! Shownotes are available @ https://zecohealth.com/gutenzymes/

Todos Medical Ltd CEO Gerald Commissiong tells Proactive said it has struck an agreement with NLC Pharma to acquire its 3CL protease biology-related assets and form a subsidiary to be known as 3CL Sciences. The subsidiary will focus on developing therapeutics, diagnostics and dietary supplements based on the 3CL protease biology work of Dorit Arad, who will be appointed chief scientific officer of the new company.

Dr Lewis is back in this bite size episode talking all about Protease Inhibitors. Essentially, Protease Inhibitors are an antiviral drug that stops the protein-cutting process which prevents a virus from multiplying. They have been prevalent in treating HIV for a number of years but now scientists have seen success in treating those infected with COVID-19. We talk all about the drug, how it works, how it's taken and a few other bits and bobs. Guest: Dr Alexander Charles Lewis Instagram and Twitter: @turnstonespod Youtube: Turning Stones Podcast Listen: Spotify, Apple & Google Podcasts and many other platforms!

Bigger is Better - The Suzanne Somers Podcast On this episode of The Suzanne Somers Podcast Suzanne reveals the new VALUE SIZE bag of her amazing GUT RENEW Superfood Protein Formula. Find out why everyone is talking about Suzanne's best-selling new product with organic, plant-based protein, gut health nutrients, immune support and more! With so many people experiencing digestive and stomach issues, Suzanne explains the importance of probiotics, prebiotics, and digestive enzymes to turn around gut health. NO MORE BLOATING! GUT RENEW contains 20 grams or organic, plant-based protein, ZERO sugars and only 3 grams of carbs. Plus, it's delicious! She and Alan enjoy a Chocolate Peanut Butter Banana smoothie that looks like a milkshake! Go to SuzanneSomers.com for GUT RENEW Superfood Protein Formula (Value Size 30-Servings!) ONLY $99.99 at SuzanneSomers.com SUZANNE™ GUT RENEW (VALUE SIZE) Superfood Protein Formula Organic Plant-Based Protein and Gut Health Support With Phyto Greens • Phyto Fruit and Vegetable Blend • Sea Minerals Each serving Includes 20 grams of protein, ZERO grams of sugar, and 3 grams of carbs! Support the critical balance of the gut with this powerhouse blend of the highest quality plant-based proteins loaded with superfoods from phyto greens, fruits and vegetables, plus the most important nutrients to support gut health.    Add to your favorite smoothie for a superfood protein burst 4 ORGANIC PLANT-BASED PROTEINS Sprouted Fermented Pea Protein • Sprouted Fermented Rice Protein Hemp Protein • Sacha Inchi Protein 5 PHYTO GREENS Chlorella • Spirulina • Young Alfafa Sprouts • Barley Grass • Wheatgrass 5 GUT HEALTH NUTRIENTS Digestive Enyzmes • Probiotic Fermented Blend • Prebiotic Jerusalem Artichoke • Triphala Blend • Marshmallow Extract Powder 5 IMMUNE SUPPORT BOOSTERS Ginger • Turmeric • Sea Buckthorn • Ceylon Cinnamon • Shiitake Mushroom 8 PHYTO FRUITS & VEGETABLES BLEND Beetroot • Carrot • Kale • Spinach • Acai • Apple • Grape • Broccoli Sprout 50+ SEA MINERALS Trace Levels of over 50 Minerals including Magnesium & Zinc ORGANIC SWEETENER Organic Stevia Leaf Extract   SERVING SUGGESTIONS: Place 2 tablespoons SUZANNE GUT RENEW + 8 oz. Coconut Milk + 1/2 cup Blueberries + Ice into blender and blend until smooth.  INGREDIENTS: Organic Sprouted Fermented Pea Protein, Organic Sprouted Brown Rice Protein, Organic Hemp Protein, Organic Sachs Inchi Protein, Organic Ceylon Cinnamon Powder, Natural Vanilla Flavor, Organic Jerusalem Artichoke Inulin Powder, Marshmallow Root Extract Powder, Aquamin. (Sea Mineral Complex Algae Powder), Organic Sea Buckthorn Juice Powder•, organic pmanthus Emblica, Organic Terminals Chebula, Organic Terminals Emblica, Organic Stevia Leaf Extract Powder, Organic Spirulina Powder, Organic Chlorella Powder, Organic Alfalfa Grass Powder, Organic Barley Grass Powder, Organic Wheatgra. Powder, Organic Ferment. Powder (Mung Bean, Brown Rice, Red Lentil, Chick Pea, Flaxseed, Millet & Quinoa)• Organic Ginger Root Powder, Organic Turmeric Root Powder, Organic D2 Shiitake Mushroom Powder, Protease, Organic Carrot Powder, Organic Beetroot Powder, Organic Kale Powder, Organic Spinach Powde•+, Organic Acai Juice Powder, Amylase, Lipase, Organic Apple Powder, Organic Grape Juice Powder, Organic Broccoli Sprout Powder, Lactase, Cellulase. US Certified Organic Australian Certified Organic + European Organic Certified  #SuzanneSomers #SUZANNEOrganics #SUZANNESelects Get the book A New Way To Age by Suzanne Somers in paperback at https://www.suzannesomers.com/products/a-new-way-to-age-paperback-book Find out what Suzanne is up to and go to SuzanneSomers.com for more info on all of her incredible products. Suzanne Somers is one of America's most popular and beloved personalities. In a multifaceted career that has spanned more than three decades, she has achieved extraordinary success as an actress, singer, comedienne, New York Times bestselling author, Las Vegas Entertainer of the Year, entrepreneur, and lecturer. She is the voice and face of alternative medicine. She received an Emmy nomination as Outstanding Host for “The SUZANNE Show,” her weekly Lifetime Network talk show, which provides a thought-provoking morning show alternative with in-depth information on health and wellness in a casual, entertaining format. Suzanne's fun, smart, empowering talk show, “Suzanne Somers' Breaking Through,” airs online on the CafeMom Studios YouTube channel. For Healthy, Clean Living Suzanne Somers has developed beauty and health products that are pure and clean, easy and fun! Suzanne Somers beauty products are made with natural botanical extracts, enzymes, skin-nurturing anti-oxidants, organic fruits, and vegetables. From nourishing skin-care to flawless make-up, these products were designed to help you glow. For an in-home fitness experience, Suzanne Somers delivers products for amazing results. Her simple, achievable guidelines for exercising and eating right help you look and feel better. With her products and fitness plans, you'll be eating right and looking great while committing to a healthier lifestyle! Be beautiful inside and out with Suzanne Somers Beauty, Health & Fitness! Find The Suzanne Somers Podcast - On YouTube, Facebook, Instagram, Apple Podcasts, Google Podcasts, Spotify, and everywhere great podcasts are found.

Todos Medical Ltd. CEO Gerald Commissiong tells Proactive it has announced positive clinical validation data for its 3CL protease biomarker assay TolloTest in a clinical study of coronavirus (COVID-19) patients. The study evaluated TolloTest's sensitivity compared with PCR tests in hospitalized COVID-19 patients, patients hospitalized for conditions other than COVID-19 and individuals exposed to confirmed COVID-19 subjects in the community outpatient setting and healthy controls.

Episode Summary: Enzymes that break down other proteins, or proteases, could be used as a powerful therapeutic if they could specifically chew-up disease causing entities. However many proteases are non-specific, breaking any protein in their path, while the specific ones target proteins that would provide no therapeutic benefit. Travis and his colleagues developed a riff on the method known as PANCE that utilizes bacteria and bacterial viruses known as phages to evolve proteins toward a specific goal. With it, he retrains the sequence-specific protease, botulinum neurotoxin, toward new targets and away from its original ones. The novel enzymes Travis generates have the potential to not only stimulate nerve regeneration but also deliver itself to the correct cell types for a whole new type of therapy. Episode Notes:About the AuthorTravis is a postdoc who performed this work in the lab of Professor David Liu at Harvard University. The Liu lab is famous for engineering and evolving proteins that can be utilized as massively impactful tools for overcoming diverse diseases.  Travis's teachers fostered a curiosity that created a passion for chemistry and ultimately led him to engineer new biochemistries. Key TakeawaysProteases are enzymes that cut up other proteins.Proteases can either be non-specific, a nuke obliterating any protein in their path,  or sequence-specific, a heat seeking missile only cutting very specific protein motifs.Sequence-specific proteases that target disease causing proteins would make great drugs but therapeutically useful proteases rarely exist in nature.Travis focuses on re-engineering the sequence-specific protease known as botulinum neurotoxin so that it cuts an entirely new, therapeutically relevant protein sequence.Using a method called PANCE that utilizes bacteria and bacterial viruses (phages), Travis trains botulinum neurotoxin toward cutting a new target and leaving its original target alone.TranslationBotulinum neurotoxin has a cutting domain that Travis engineered toward a therapeutically relevant target, and a targeting domain that delivers the protein toward neurons.The enzymes generated could be used to cure neural pathologies but the PANCE could also be applied to change which cell type the protease targets, creating a highly programmable therapeutic protease platform.The platform has a ton of interest from industry and Travis is continuing to work on it outside of academia so that these proteases make it to the clinic and impact patient lives.First Author: Travis BlumPaper: Phage-assisted evolution of botulinum neurotoxin proteases with reprogrammed specificity

In this week's episode, we will review an integrated analysis of one of the largest adult BCR-ABL1-negative B-ALL patient cohorts treated in a single trial, learn more about the genotypic and phenotypic features of patients with clonal cytopenias, and look at a study showing that a serine protease expressed in the placenta cleaves α1-antitrypsin to generate a fragment that inhibits formation of neutrophil extracellular traps in neonates.

In episode 66 of HealingMatter, Jason talks about Carpal Tunnel, Tingling Hands, and Holistic Options. Carpal Tunnel symptoms are tingling hands/fingers, numbness, cold hands, weak grip/can't hold little things like a sheet of paper, and a painful, weak wrist. Carpal Tunnel can be from a pinched nerve further up the "line", weak adrenal glands, inflammation from viral or bacterial infections, and/or Candida. There are many other options other than surgery like Chiropractic, Massage Therapy, Yoga, and Dietary Changes. There are also many Premier Research Labs Supplements that can be purchased at www.StrategicHealing.us that can help alleviate Carpal Tunnel. Just because your wrist hurts doesn't mean that the root of the pain is stemming from the wrist. Your body has nerves that run from the brain all the way to your fingertips and tips of your toes. A pinched nerve causes pain and swelling/inflammation. A pinched nerve in your neck, jaw, shoulder, elbow, or wrist can cause Carpal Tunnel. Surgery might not remove the pain on the first attempt. The more surgeries you have, the more the scar tissue builds up and the more nerves that can be affected by the pressure from the scar tissue. Thoracic Outlet Syndrome will cause Carpal Tunnel like symptoms. Surgery will not help alleviate the pain because it is caused by tight muscles. A stiff neck or forward head posture can cause pain in the wrist. An intestinal infection can cause inflammation and swelling in the joints. Joints are the most affected because they have the least amount of blood flow. A weak Adrenal System can cause joint pain because the adrenals control the tightness of the tendons. Another thing that can cause joint pain is viruses. Viruses can hang out in the joints because of the lack of blood flow. The AntiViral dies will help reduce inflammation. The AntiViral diet will also help remove Candida. People that eat a lot of sugar and carbohydrates create an environment that feeds infection and produces inflammation. Constipation also causes inflammation because your body holds onto and reabsorbs toxins. There are many holistic practices that help remove inflammation and toxins. Chiropractic will help realign the skeletal system. Massage Therapy, Yoga, and Stretching will help squeeze toxins out of the joints. Nutrition will create an environment where infection isn't "fed." Premier Research Labs Supplements can help clean out scar tissue, fight infection, and more. Please help support more shows like this by purchasing Premier Research Labs supplements from my online store at www.StrategicHealing.us/shop Supplements mentioned in today's show: EFA's, DHA, Zinc, AdrenaVen, Pink Salt, Magnesium, and Protease. Epsom Salt Bath Recipe: Four pounds of Epsom Salt in a warm/hot bath tub. Soak for 30 to 60 minutes. Relax! Old vaccinations on the shoulder can also cause Carpal Tunnel symptoms because scar tissue may have built up at the injection site. Scar tissue and old injuries will block the body's energetic flow. There is a technique I am skilled in called I-Packs (mud packs). This very specific technique is guided by muscle testing to help identify the exact injured area. It can be rejuvenated with minerals and help restore the energetic flow. Did you learn something new? Help me make more shows by purchasing supplements mentioned in today's show at www.StrategicHealing.us/shop/ * Support your health by becoming a Patron for as little as $1/month: www.patreon.com/JasonEagleQRA You can get even more in depth answers to your health questions answered directly by Jason. You'll also get a sneak peak into the Healing Homestead! * Join me LIVE at noon on Wednesday! www.facebook.com/JasonEagleQRA/

Dr. Burkhead, infectious diseases fellow at the University of South Florida, covers HIV History, the development of HIV antiviral therapy, and current treatment strategies in this comprehensive update. Dr. Burkhead begins by reviewing the different classes of antiretrovirals. He then traces the chronological history of antiretroviral development, from the initial trials of AZT through the introduction of other NRTIs, Protease inhibitors, NNRTIs, and the Integrase inhibitors. Next, Dr. Burkhead discusses antiretroviral therapy in special situations, such as in those who are pregnant, have chronic kidney disease, or cardiac disease. Important antiretroviral mutations are also discussed. Lastly, Dr. Burkhead closes the talk by discussing future directions for antiretroviral therapy.

TWiV 688: We put COVID-19 papers through a sieve December 2, 2020 On this episode, UK grants EUA for Pfizer vaccine, advice for CDC on who to immunize first, news from Das Coronavirus, SARS-CoV-2 protease regulates innate responses, and viral mRNAs are not an indication of viral replication. Hosts: Vincent Racaniello, Rich Condit, Kathy Spindler, and Brianne Barker Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode UK grants EUA for Pfizer vaccine (NY Times) ACIP advice on who to vaccinate first (NY Times) Das coronavirus update SARS-CoV-2 protease regulates innate response (Nature) Viral mRNAs do not indicate viral replication (Nat Comm) Addendum to SARS-CoV-2 discovery paper (Nature) 16:15 SARS-CoV-2 mRNA vaccine and GC formation (Immunity) 29:35 What scientists say about masks (NY Times) 1:29:03 Letters read on TWiV 688 Timestamps by Jolene. Thanks! Weekly Picks Brianne – Pedromics Kathy – Global map at Mars opposition Rich – Janeway’s Immunobiology Vincent – Janet Iwasa’s Animation Lab Listener Pick Cheryl – BioRender.com holiday card templates Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv

TWiV 688: We put COVID-19 papers through a sieve December 2, 2020 On this episode, UK grants EUA for Pfizer vaccine, advice for CDC on who to immunize first, news from Das Coronavirus, SARS-CoV-2 protease regulates innate responses, and viral mRNAs are not an indication of viral replication. Hosts: Vincent Racaniello, Rich Condit, Kathy Spindler, and Brianne Barker Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode UK grants EUA for Pfizer vaccine (NY Times) ACIP advice on who to vaccinate first (NY Times) Das coronavirus update SARS-CoV-2 protease regulates innate response (Nature) Viral mRNAs do not indicate viral replication (Nat Comm) Addendum to SARS-CoV-2 discovery paper (Nature) 16:15 SARS-CoV-2 mRNA vaccine and GC formation (Immunity) 29:35 What scientists say about masks (NY Times) 1:29:03 Letters read on TWiV 688 Timestamps by Jolene. Thanks! Weekly Picks Brianne – Pedromics Kathy – Global map at Mars opposition Rich – Janeway’s Immunobiology Vincent – Janet Iwasa’s Animation Lab Listener Pick Cheryl – BioRender.com holiday card templates Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv

SLAS Discovery 25.10 December 2020Rob Howes discusses the paper "High-Throughput Screening for Drugs That Inhibit Papain-Like Protease in SARS-CoV-2" with authors Meredith Gardner (Scripps Research) and Michael Farzan (Scripps Research). This research is part of the December Special Issue, Drug Discovery Targeting COVID-19 with Associate Editor Tim Spicer.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.12.378422v1?rss=1 Authors: Guenther, S., Reinke, P. Y. A., Fernandez-Garcia, Y., Lieske, J., Lane, T. J., Ginn, H., Koua, F., Ehrt, C., Ewert, W., Oberthuer, D., Yefanov, O., Meier, S., Lorenzen, K., Krichel, B., Kopicki, J., Gelisio, L., Brehm, W., Dunkel, I., Seychell, B., Gieseler, H., Norton-Baker, B., Escudero-Perez, B., Domaracky, M., Saouane, S., Tolstikova, A., White, T., Haenle, A., Groessler, M., Fleckenstein, H., Trost, F., Galchenkova, M., Gevorkov, Y., Li, C., Awel, S., Peck, A., Barthelmess, M., Schluenzen, F., Lourdu, X. P., Werner, N., Andaleeb, H., Ullah, N., Falke, S., Srinivasan, V., Franca, B., Schwi Abstract: The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of repurposing drug libraries containing 5953 individual compounds against the SARS-CoV-2 main protease (Mpro), which is a potent drug target as it is essential for the virus replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. Interestingly, two compounds bind outside the active site to the native dimer interface in close proximity to the S1 binding pocket. Another compound binds in a cleft between the catalytic and dimerization domain of Mpro. Neither binding site is related to the enzymatic active site and both represent attractive targets for drug development against SARS-CoV-2. This X-ray screening approach thus has the potential to help deliver an approved drug on an accelerated time-scale for this and future pandemics. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.11.378646v1?rss=1 Authors: Lee, W. H., Liu, W., Fan, J.-S., Yang, D. Abstract: The viral protease domain (NS3pro) of dengue virus is essential for virus replication and its cofactor NS2B is indispensable for the proteolytic function. Although several NS3pro-NS2B complex structures have been obtained, the dynamic property of the complex remains poorly understood. Using NMR relaxation techniques, here we found that NS3pro-NS2B exists in both closed and open conformations which are in dynamic equilibrium on a sub-millisecond timescale in aqueous solution. Our structural information indicates that the C-terminal region of NS2B is disordered in the open conformation but folded in the closed conformation. Using mutagenesis, we showed that the closed-open conformational equilibrium can be shifted by changing NS2B stability. Moreover, we revealed that the proteolytic activity of NS3pro-NS2B correlates well with the population of the closed conformation. Our results suggest that the closed-open conformational equilibrium can be used by both nature and man to control the replication of dengue virus. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.10.363747v1?rss=1 Authors: Johe, P., Jaenicke, E., Neuweiler, H., Schirmeister, T., Kersten, C., Hellmich, U. A. Abstract: Rhodesain is the lysosomal cathepsin L-like cysteine protease of T. brucei rhodesiense, the causative agent of Human African Trypanosomiasis. The enzyme is essential for the proliferation and pathogenicity of the parasite as well as its ability to overcome the blood-brain barrier of the host. Lysosomal cathepsins are expressed as zymogens with an inactivating pro-domain that is cleaved under acidic conditions. A structure of the uncleaved maturation intermediate from a trypanosomal cathepsin L-like protease is currently not available. We thus established the heterologous expression of T. brucei rhodesiense pro-rhodesain in E. coli and determined its crystal structure. The trypanosomal pro-domain differs from non-parasitic pro-cathepsins by a unique, extended -helix that blocks the active site and whose interactions resemble that of the antiprotozoal inhibitor K11777. Interdomain dynamics between pro- and core protease domain as observed by photoinduced electron transfer fluorescence correlation spectroscopy increase at low pH, where pro-rhodesain also undergoes autocleavage. Using the crystal structure, molecular dynamics simulations and mutagenesis, we identify a conserved interdomain salt bridge that prevents premature intramolecular cleavage at higher pH values and may thus present a control switch for the observed pH-sensitivity of pro-enzyme cleavage in (trypanosomal) CathL-like proteases. Copy rights belong to original authors. Visit the link for more info

Today on Mushroom Hour we have the honor of chatting with and learning from Eleana Hsu. Eleana is a fermentress focused on transforming foods with the magic of microbes and koji. What makes her most excited is creating new food products and flavors using local produce, different types of beans, and whole utilization techniques. Eleana has experience teaching koji workshops in the Bay Area and crafting ferments for local popup dinners and events. Koji is a filamentous fungi that has been used to ferment food since 300 BC. By employing this wondrous organism in a sort of alchemical, culinary transmutation may play a big role in the future of food as we know it. Currently, she is working on launching unique great tasting fermented food products in the Bay Area with her company Shared Cultures. Topics Covered:Curing Depression by Foraging in Nature Mushroom Hunting & Favorite Edibles SOMA Camp Fermentation – Transforming our Food with Microorganisms The Magic of Koji Enzymes Lipase, Protease, Amylase Fermenting Inspirations Uncovering a Family History with Koji Chinese Cuisine made with Koji Fermented Fungi as the Future of Food How to Make Miso and Soy Sauce Lessons from Becoming an Entrepreneur Finding Fulfillment Shared Cultures Products & Future Projects Episode Resources: Shared Cultures Website: https://www.shared-cultures.com/ Shared Cultures IG: https://www.instagram.com/sharedcultures/ Eugenia Bone "Mycophilia" (Book): https://www.amazon.com/Mycophilia-Revelations-Weird-World-Mushrooms/dp/1609619870 Sander Katz (inspiration): https://www.wildfermentation.com/ "Noma Guide to Fermentation" (Book): https://www.amazon.com/Noma-Guide-Fermentation-lacto-ferments-Foundations/dp/1579657184 Jeremy Umansky "Koji Alchemy" (Book): https://www.amazon.com/Koji-Alchemy-Rediscovering-Mold-Based-Fermentation/dp/160358868X Russula Brevipes (Mushroom): https://www.mushroomexpert.com/russula_brevipes.html Boletus Edulis (Mushroom): https://www.mushroomexpert.com/boletus_edulis.html

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.06.369439v1?rss=1 Authors: Strömich, L., Wu, N., Barahona, M., Yaliraki, S. N. Abstract: Inhibiting the main protease of SARS-CoV-2 is of great interest in tackling the COVID-19 pandemic caused by the virus. Most efforts have been centred on inhibiting the binding site of the enzyme. However, considering allosteric sites, distant from the active or orthosteric site, broadens the search space for drug candidates and confers the advantages of allosteric drug targeting. Here, we report the allosteric communication pathways in the main protease dimer by using two novel fully atomistic graph theoretical methods: Bond-to-bond propensity analysis, which has been previously successful in identifying allosteric sites without a priori knowledge in benchmark data sets, and, Markov transient analysis, which has previously aided in finding novel drug targets in catalytic protein families. We further score the highest ranking sites against random sites in similar distances through statistical bootstrapping and identify four statistically significant putative allosteric sites as good candidates for alternative drug targeting. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.06.370916v1?rss=1 Authors: Qin, B., Craven, G. B., Hou, P., Lu, X., Child, E. S., Morgan, R. M. L., Armstrong, A., Mann, D. J., Cui, S. Abstract: RNA viruses are critically dependent upon virally encoded proteases that cleave the viral polyproteins into functional mature proteins. Many of these proteases are structurally conserved with an essential catalytic cysteine and this offers the opportunity to irreversibly inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that selectively target the active site cysteine of the 3C protease (3Cpro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we effectively re-purpose these hits towards the main protease (Mpro) of SARS-CoV-2 which shares the 3C-like fold as well as similar catalytic-triad. We demonstrate that the hit fragments covalently link to the catalytic cysteine of Mpro to inhibit its activity. In addition, we provide the first demonstration that targeting the active site cysteine of Mpro can also have profound allosteric effects, distorting secondary structures required for formation of the active dimeric unit of Mpro. These new data provide novel mechanistic insights into the design of EV71 3Cpro and SARS-CoV-2 Mpro inhibitors and identify acrylamide-tagged pharmacophores for elaboration into more selective agents of therapeutic potential. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.31.363309v1?rss=1 Authors: Weng, Y. L., Naik, S. R., Dingelstad, N., Kalyaanamoorthy, S., Ganesan, A. Abstract: The 2019 novel coronavirus pandemic caused by SARS-CoV-2 remains a serious health threat to humans and a number of countries are already in the middle of the second wave of infection. There is an urgent need to develop therapeutics against this deadly virus. Recent scientific evidences have suggested that the main protease (Mpro) enzyme in SARS-CoV-2 can be an ideal drug target due to its crucial role in the viral replication and transcription processes. Therefore, there are ongoing research efforts to identify drug candidates against SARS-CoV-2 Mpro that resulted in hundreds of X-ray crystal structures of ligand bound Mpro complexes in the protein data bank (PDB) that describe structural details of different chemotypes of fragments binding within different sites in Mpro. In this work, we perform rigorous molecular dynamics (MD) simulation of 62 reversible ligand-Mpro complexes in the PDB to gain mechanistic insights about their interactions at atomic level. Using a total of ~2.25 microseconds long MD trajectories, we identified and characterized different pockets and their conformational dynamics in the apo Mpro structure. Later, using the published PDB structures, we analyzed the dynamic interactions and binding affinity of small ligands within those pockets. Our results identified the key residues that stabilize the ligands in the catalytic sites and other pockets in Mpro. Our analyses unraveled the role of a lateral pocket in the catalytic site in Mpro that is critical for enhancing the ligand binding to the enzyme. We also highlighted the important contribution from HIS163 in this lateral pocket towards ligand binding and affinity against Mpro through computational mutation analyses. Further, we revealed the effects of explicit water molecules and Mpro dimerization in the ligand association with the target. Thus, comprehensive molecular level insights gained from this work can be useful to identify or design potent small molecule inhibitors against SARS-CoV-2 Mpro. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.29.339317v1?rss=1 Authors: The COVID Moonshot Consortium,, Achdout, H., Aimon, A., Bar-David, E., Barr, H., Ben-Shmuel, A., Bennett, J., Bobby, M. L., Brun, J., BVNBS, S., Calmiano, M., Carbery, A., Cattermole, E., Chodera, J. D., Clyde, A., Coffland, J. E., Cohen, G., Cole, J., Contini, A., Cox, L., Cvitkovic, M., Dias, A., Douangamath, A., Duberstein, S., Dudgeon, T., Dunnett, L., Eastman, P. K., Erez, N., Fairhead, M., Fearon, D., Fedorov, O., Ferla, M., Foster, H., Foster, R., Gabizon, R., Gehrtz, P., Gileadi, C., Giroud, C., Glass, W. G., Glen, R., Glinert, I., Gorichko, M., Gorrie-Stone, T., Griffen, E. J., Heer Abstract: Herein we provide a living summary of the data generated during the COVID Moonshot project focused on the development of SARS-CoV-2 main protease (Mpro) inhibitors. Our approach uniquely combines crowdsourced medicinal chemistry insights with high throughput crystallography, exascale computational chemistry infrastructure for simulations, and machine learning in triaging designs and predicting synthetic routes. This manuscript describes our methodologies leading to both covalent and non-covalent inhibitors displaying protease IC50 values under 150 nM and viral inhibition under 5 uM in multiple different viral replication assays. Furthermore, we provide over 200 crystal structures of fragment-like and lead-like molecules in complex with the main protease. Over 1000 synthesized and ordered compounds are also reported with the corresponding activity in Mpro enzymatic assays using two different experimental setups. The data referenced in this document will be continually updated to reflect the current experimental progress of the COVID Moonshot project, and serves as a citable reference for ensuing publications. All of the generated data is open to other researchers who may find it of use. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.347534v1?rss=1 Authors: Mellott, D., Tseng, C.-T., Drelich, A., Fajtova, P., Chenna, B. C., Kostomiris, D., Hsu, J. C., Zhu, J., Taylor, Z., Tat, V., Katzfuss, A., Li, L., Giardini, M. A., Skinner, D., Hirata, K., Beck, S., Carlin, A. F., Clark, A. E., Berreta, L., Maneval, D., Frueh, F., Hurst, B. L., Wang, H., Kocurek, K. I., Raushel, F. M., O'Donoghue, A., Siqueira-Neto, J. L., Meek, T. D., McKerrow, J. H. Abstract: K777 is a di-peptide analog that contains an electrophilic vinyl-sulfone moiety and is a potent, covalent inactivator of cathepsins. Vero E6, HeLa/ACE2, Caco-2, A549/ACE2, and Calu-3, cells were exposed to SARS-CoV-2, and then treated with K777. K777 reduced viral infectivity with EC50 values of inhibition of viral infection of: 74 nM for Vero E6,

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.11.335299v1?rss=1 Authors: Gobeil, S., Janowska, K., McDowell, S., Mansouri, K., Parks, R., Manne, K., Stalls, V., Kopp, M., Henderson, R., Edwards, R. J., Haynes, B. F., Acharya, P. Abstract: The SARS-CoV-2 spike (S) protein is the target of vaccine design efforts to end the COVID-19 pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic, and are now the dominant form worldwide. Here, we analyze the D614G mutation in the context of a soluble S ectodomain construct. Cryo-EM structures, antigenicity and proteolysis experiments suggest altered conformational dynamics resulting in enhanced furin cleavage efficiency of the G614 variant. Furthermore, furin cleavage alters the conformational dynamics of the Receptor Binding Domains (RBD) in the G614 S ectodomain, demonstrating an allosteric effect on the RBD dynamics triggered by changes in the SD2 region, that harbors residue 614 and the furin cleavage site. Our results elucidate SARS-CoV-2 spike conformational dynamics and allostery, and have implications for vaccine design. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.12.335885v1?rss=1 Authors: Jarvela, T. S., Chaplot, K., Lindberg, I. Abstract: Alpha-synuclein pre-formed fibrils (PFFs) represent a promising model system for the study of cellular processes underlying cell-to- cell transmission of -synuclein proteopathic aggregates. However, the ability to differentiate the fate of internalized PFFs from those which remain in the extracellular environment remains limited due to the propensity for PFFs to adhere to the cell surface. Removal of PFFs requires repeated washing or specific quenching of extracellular fluorescent PFF signals. In this paper we present a new method for analyzing the fate of internalized -synuclein. We inserted a tobacco etch virus (TEV) protease cleavage site between -synuclein and green fluorescent protein. As the TEV protease is highly specific, non-toxic, and active under physiological conditions, we are able to use protection from TEV cleavage to distinguish internalized PFFs from those which remain attached to the cell surface. Using this experimental paradigm, downstream intracellular events can be analyzed via live or fixed cell microscopy as well as by Western blotting. We suggest that this method will be useful for understanding the fate of PFFs after endocytosis under various experimental manipulations. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.05.326363v1?rss=1 Authors: Shaofan, H., Yuancai, X., Lu, Q., Meng, W., Zhang, Y. Abstract: The membrane-bound transcription factor Nrf1 (i.e., encoded by Nfe2l1) is activated by sensing glucose deprivation, cholesterol excess, proteasomal inhibition and oxidative stress, and then mediates distinct signaling responses in order to maintain cellular homeostasis. Here, we found that Nrf1 stability and transactivity are enhanced by USP19, a tail-anchored ubiquitin-specific protease in the endoplasmic reticulum (ER). Further experiments revealed that USP19 directly interacts with Nrf1 in proximity to the ER and acts as a deubiquitinating enzyme to remove ubiquitin moieties from this protein and hence circumvent potential proteasomal degradation. Such USP19-mediated effect takes place only after Nrf1 is retrotranslocated by p97 out of ER membranes. Conversely, knockout of USP19 causes significant decreases in Nrf1 abundance and its active isoform entering the nucleus, resulting in down-regulation of its target proteasomal subunits. This led to a modest reduction of USP19-/-derived tumor growth in xenograft mice, when compared with wild-type controls. Altogether, these demonstrate that USP19 serves as a novel mechanistic modulator of Nrf1, but not Nrf2. In turn, our additional evidence has also unraveled that transcriptional expression of endogenous USP19 and its promoter-driven reporter genes is regulated by Nrf2, as well by Nrf1, at distinct layers within a complex hierarchical regulatory network. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.29.318683v1?rss=1 Authors: Sanchez-Lanzas, R., Castano, J. G. Abstract: DJ-1/PARK7 mutations are linked with familial forms of early onset Parkinson disease (PD). We have studied the degradation of untagged DJ-1 WT and missense mutants in mouse embryomic fibroblasts obtained from DJ-1 null mice, an approach closer to the situation in patients carrying homozygous mutations. The results showed that the mutants: L10P, M26I, A107P, P158DEL, L166P, E163K and L172Q are unstable proteins, while A39S, E64D, R98Q, A104T, D149A, A171S, K175E and A179T are as stable as the DJ-1 WT. Inhibition of proteasomal and autophagic-lysosomal pathways had little effect on their degradation. Immunofluorescence and biochemical fractionation studies indicated that M26I, A107P, P158DEL, L166P, E163K and L172Q mutants associate with mitochondria. Silencing of mitochondrial matrix protease LonP1 produced a strong reduction of the degradation of those mitochondrialy associated DJ-1 mutants, but not of mutant L10P. These results demonstrated a mitochondrial pathway of degradation of those DJ-1 missense mutants implicated in PD pathogenesis. Copy rights belong to original authors. Visit the link for more info