Podcasts about pathogenicity

In this encore episode, we detail the intestinal mycobiome and the mechanisms by which beneficial microbes aid in regulating opportunistic fungal species: Candida albicans. We discuss Candida overgrowth virulence and how disruptions in microbial balance, immune function, and epithelial integrity impact Candida's pathogenicity. Additionally, we discuss the role of mast cells in the lamina propria, their involvement in mucosal immunity, and how Mast Cell Activation Syndrome (MCAS) can be exacerbated by fungal dysbiosis / microbial imbalances.Topics: 1. Introduction - The intestinal mycobiome and its role in intestinal health.  - Regulating populations of opportunistic fungal species like Candida albicans.- Mast cell activation syndrome (MCAS) intro.   2. Structure of the Intestinal Barrier- The microbiome and mucus layer: microbes, mucins, antimicrobial peptides, sIgA.- The epithelial monolayer: enterocytes, goblet cells, Paneth cells, enteroendocrine cells…- Tight junction proteins and paracellular transport.- The lamina propria beneath the epithelium: immune cells and more. 3. Candida's Pathogenicity and Barrier Disruption- Exists primarily in its yeast form, regulated by microbial competition, host immune defenses, antifungal peptides.  - Secretory IgA (sIgA) and immune surveillance mechanisms help regulate fungal populations. - Chronic stress, immune suppression, and dysbiosis can deplete sIgA, increasing susceptibility to Candida proliferation.  - Environmental triggers such as immune suppression, microbial depletion, inflammatory cytokines.- Yeast-to-hyphal transition, deeper tissue invasion.  - Secreted aspartyl proteinases (SAPs), phospholipases, candidalysin: epithelial damage.- Pattern recognition receptors (PRRs) and overgrowth detection. 4. Impact of Beneficial Bacteria on Candida Overgrowth  - Beneficial bacteria compete with Candida for nutrients and epithelial adhesion sites.  - Short-chain fatty acids (SCFAs) produced by beneficial bacteria.- Depletion of beneficial bacteria removes ecological resistance, allowing Candida to proliferate unchecked.   5. Mast Cells in the Lamina Propria and Their Role in Intestinal Immunity- Mast cell location - Upon activation, mast cells release histamine, cytokines, proteases, and more that regulate gut immune responses.  - Histamine can increase gut permeability and modulate local immune activation.  - Tryptase and chymase. - Pro-inflammatory cytokines.  6. Mast Cell Activation Syndrome (MCAS) - Mast cell hyperactivation.- Environmental triggers, toxins, chronic infections, and stress. - Candida overgrowth and mast cell activation.- Addressing microbial imbalances and reducing the body's total microbial, chemical, and toxin burden.- A diverse microbiome.   7. Conclusion- Candida overgrowth and regulation via immune defenses and beneficial bacterial competition.- MCAS, root cause approach.Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠

In this episode, we detail the intestinal mycobiome and the mechanisms by which beneficial microbes aid in regulating opportunistic fungal species: Candida albicans. We discuss Candida overgrowth virulence and how disruptions in microbial balance, immune function, and epithelial integrity impact Candida's pathogenicity. Additionally, we discuss the role of mast cells in the lamina propria, their involvement in mucosal immunity, and how Mast Cell Activation Syndrome (MCAS) can be exacerbated by fungal dysbiosis / microbial imbalances.Topics: 1. Introduction - The intestinal mycobiome and its role in intestinal health.  - Regulating populations of opportunistic fungal species like Candida albicans.- Mast cell activation syndrome (MCAS) intro.   2. Structure of the Intestinal Barrier- The microbiome and mucus layer: microbes, mucins, antimicrobial peptides, sIgA.- The epithelial monolayer: enterocytes, goblet cells, Paneth cells, enteroendocrine cells…- Tight junction proteins and paracellular transport.- The lamina propria beneath the epithelium: immune cells and more. 3. Candida's Pathogenicity and Barrier Disruption- Exists primarily in its yeast form, regulated by microbial competition, host immune defenses, antifungal peptides.  - Secretory IgA (sIgA) and immune surveillance mechanisms help regulate fungal populations. - Chronic stress, immune suppression, and dysbiosis can deplete sIgA, increasing susceptibility to Candida proliferation.  - Environmental triggers such as immune suppression, microbial depletion, inflammatory cytokines.- Yeast-to-hyphal transition, deeper tissue invasion.  - Secreted aspartyl proteinases (SAPs), phospholipases, candidalysin: epithelial damage.- Pattern recognition receptors (PRRs) and overgrowth detection. 4. Impact of Beneficial Bacteria on Candida Overgrowth  - Beneficial bacteria compete with Candida for nutrients and epithelial adhesion sites.  - Short-chain fatty acids (SCFAs) produced by beneficial bacteria.- Depletion of beneficial bacteria removes ecological resistance, allowing Candida to proliferate unchecked.   5. Mast Cells in the Lamina Propria and Their Role in Intestinal Immunity- Mast cell location - Upon activation, mast cells release histamine, cytokines, proteases, and more that regulate gut immune responses.  - Histamine can increase gut permeability and modulate local immune activation.  - Tryptase and chymase. - Pro-inflammatory cytokines.  6. Mast Cell Activation Syndrome (MCAS) - Mast cell hyperactivation.- Environmental triggers, toxins, chronic infections, and stress. - Candida overgrowth and mast cell activation.- Addressing microbial imbalances and reducing the body's total microbial, chemical, and toxin burden.- A diverse microbiome.   7. Conclusion- Candida overgrowth and regulation via immune defenses and beneficial bacterial competition.- MCAS, root cause approach.Thank you to our episode sponsor:1. Shop ⁠⁠⁠⁠⁠Fresh Press Farms⁠⁠⁠'⁠⁠⁠⁠Peach Cider Vinegar⁠⁠ at Sprouts locations nationwide, and check out their full collection ⁠⁠⁠⁠⁠here⁠⁠⁠⁠⁠. Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠

In today's episode, we explore the complex interactions between Candida and the gastrointestinal tract, examining how this fungus can transition from harmless commensal to pathogenic state that disrupts gut barrier functions. We dive into Candida's ability to undermine mucosal integrity through the production of candidalysin and other virulence factors like secreted aspartyl proteases, which specifically target and degrade tight junction proteins such as claudins and occludins. We'll explore the layered structure of the intestinal mucus barrier, its role in immunological defense, and how Candida's biofilm-forming capabilities further facilitate its pathogenicity. Lastly, we'll discuss tools and strategies for mitigating Candida overgrowth. Topics: 1. Gastrointestinal Tract Anatomy / Barrier Function - Mucus Layer - Description of the gastroprotective mucus barrier - Differences in mucus architecture between the small and large intestines - Composition: mucins, immunoglobulins (IgA), antimicrobial peptides - Intestinal Epithelium - Structure and function of the epithelial cell layer - Roles of different epithelial cells: enterocytes, goblet cells, enteroendocrine cells, Paneth cells - Lamina Propria - Immune cell types 2. Integrity of Tight Junctions - Tight junction proteins: claudins, occludins, junctional adhesion molecules (JAMs) - Mechanisms of tight junction regulation and response to changes in the gut environment - Impact of physiological and pathological factors on tight junction dynamics 3. Candida Pathogenicity Mechanisms - Adherence and Biofilm Formation - Mechanisms facilitating Candida adherence to epithelial cells - Structural and functional implications of biofilm formation - Enzymatic Disruption of Tight Junctions - Role of Candida-secreted aspartyl proteases (Sap) and phospholipases in degrading tight junction components - Immune System Interaction - Triggering of inflammatory cytokines by Candida presence and their effects on gut barrier function 4. Candidalysin: A Specific Virulence Factor - Genetic basis for candidalysin production via the ECE1 gene - Mechanism of action: disruption of epithelial cell membrane integrity, pore formation, and cellular damage 5. Clinical Manifestations of Candida Overgrowth - Gastrointestinal symptoms: bloating, gas, diarrhea, constipation, abdominal pain - Systemic effects: fatigue, brain fog, skin issues, mood disturbances - Nutrient absorption impairments leading to deficiencies 6. Strategies - Biofilm Disruption - Agents targeting biofilm integrity and adherence properties - Antifungal and Enzymatic Tools - Natural antifungals - Role of enzymatic supplements in biofilm and cell wall degradation - Immune Modulation and Gut Microbiota Support - Immune-modulating agents - Probiotics and prebiotics to restore and maintain healthy gut flora Thank you to our episode sponsors: 1. Check out ⁠⁠Daily Nouri⁠⁠ and use code ⁠⁠CHLOE20⁠⁠ for 20% off your order. 2. Check out ⁠⁠⁠⁠⁠⁠⁠Liver Medic ⁠and use code Chloe20 to save 20% on ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠"Leaky Gut Repair"⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Brendan's YouTube Channel⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://x.com/livermedic⁠⁠⁠⁠⁠⁠⁠⁠⁠ Thanks for tuning in! Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

In our latest podcast, Antonia Ribes, Frederic Tort, and Gerard Muñoz-Pujol discuss CRISPR/Cas9 based technique for the validation of genetic variants requiring just the genetic data. CRISPR/Cas9-based functional genomics strategy to decipher the pathogenicity of genetic variants in inherited metabolic disorders Gerard Muñoz-Pujol, et al https://doi.org/10.1002/jimd.12681

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.29.547007v1?rss=1 Authors: Anders, J., König, C., Lender, C., Hellhund, A., Nehls, S., Shalabi, I., Honecker, B., Lorenzen, S., Meyer, M., Matthiesen, J., Cadar, D., Roeder, T., Metwally, N. G., Lotter, H., Bruchhaus, I. Abstract: Recently, two genes involved in pathogenicity in a mouse model of amoebic liver abscess were identified based on their differential expression between non-pathogenic (A1np) and pathogenic (B2p) clones of the Entamoeba histolytica isolate HM:1-IMSS. While overexpression of a gene encoding the metallopeptidase EhMP8-2 decreases the virulence of the pathogenic clone B2p, overexpression of the gene ehi_127670 (ehhp127), encoding a hypothetical protein, increases the virulence of the non-pathogenic clone A1np, while silencing this gene in B2p decreases virulence. To understand the role of both molecules in determining the pathogenicity of E. histolytica, silencing and overexpression transfectants were characterized in detail. Silencing of ehmp8-2, of the homologous gene ehmp8-1, or of both together in A1np trophozoites significantly altered the transcript levels of 60-350 genes. This strong change in the expression profile caused by the silencing of ehmp8-1 and/or ehmp8-2 implies that these peptidases regulate expression of numerous genes. Consequently, numerous phenotypic characteristics including cytopathic, hemolytic and cysteine peptidase activity were changed in response to their silencing. Silencing of ehhp127 in B2p trophozoites did not affect other genes, whereas overexpression in A1np trophozoites results in an altered expression of approximately 140 genes. EhHP127 appears to be important for trophozoite movement, as silencing negatively affects and overexpression positively affects trophozoite motility. Interestingly, the specific silencing of ehhp127 also impairs cytopathic activity, cysteine peptidase and hemolytic activity. All three molecules of interest, namely EhMP8-1, EhMP8-2, and EhHP127 can be detected in amoeba vesicles. Our results clearly show that the proteins studied here influence the pathogenicity of amoebae in different ways and use entirely different mechanisms to do so. Author summary: The human pathogen Entamoeba histolytica can live asymptomatically in the intestine or become invasive and cause fatal liver abscesses. Approximately 15,000 people die each year as a result of an amoebic infection. Recently, two clones with different pathogenicity (A1np: non-pathogenic; B2p: pathogenic) derived from the E. histolytica isolate HM:1-IMSS were compared at the transcriptome level. Two highly differentially expressed genes (ehhp127 encoding a hypothetical protein and ehmp82 encoding a metallopeptidase) were identified. Analysis of E. histolytica transfectants showed that silencing of ehhp127 and overexpression of ehmp8-2 in B2p trophozoites reduced amoebic liver abscess formation in the mouse model. In this study, we characterized E. histolytica silencing and overexpression transfectants of ehmp8-2, as well as of the homologous gene ehmp8-1 and of ehhp127. It was shown that the altered expression of the metallopeptidase genes has a strong influence on the expression of a large number of genes and that the phenotype is strongly altered as a result. Silencing of ehhp127 does not affect the overall expression profile. However, specific silencing has a negative effect on motility, cysteine peptidase, hemolytic and cytopathic activity. All three molecules were shown to be localized in trophozoite vesicles. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

英语新闻｜新型变异毒株“地狱犬”来了？中疾控回应The BQ.1 subvariant of Omicron has emerged on the mainland but no marked increase in its pathogenicity has been reported, and reinfection with COVID-19 does not increase the risk of severe illness, health officials and experts said. 卫生官员和专家表示，奥密克戎的亚分支BQ.1已在中国大陆出现，但其致病性没有明显增加，新冠肺炎的二次感染不会增加重症风险。The mainland has reported 49 cases of BQ.1 or its sublineages in nine provincial-level regions. However, no widespread transmission has been reported and no infected patients have been found to suffer more severe symptoms compared with patients who've contracted other variants.目前我国已在9个省份的本土病例中检出BQ.1及其亚分支49例，但尚未广泛流行，所致病例数较少，也未观察到感染BQ.1后临床严重程度较其它变异株增加。"Currently, the dominant strains in circulation in China remain BA.5.2 and BF.7, and both are sublineages of BA.5," the Chinese Center for Disease Control and Prevention said on Tuesday.“我国现阶段流行的毒株仍以BA.5的亚分支BA.5.2和BF.7为主。”中国疾病预防控制中心12月13日表示。The center made the statement in response to online rumors that BQ.1 and its offshoots were wreaking havoc in Japan with their high transmissibility and high death rates.网络流传消息称，一种名为BQ.1.1的新型变异毒株在日本“杀疯了”，该毒株的传染性和致死率都很高。中国疾控对此做出了回应。BQ.1, which also belongs to the BA.5 family, was first detected in Nigerian patients in June and began spreading in September in Europe and the United States, and gradually rose to become the dominant variant. Since mid-October, Asian countries, including Japan and Singapore, have been registering BQ.1 infections.BQ.1是奥密克戎BA.5的亚分支，2022年6月在尼日利亚感染者中发现，9月开始BQ.1及其衍生的子代亚分支在欧美国家流行，占比逐月升高，10月中旬在日本和新加坡等亚洲国家逐渐开始流行。"While BQ.1 has drawn global attention, no country has ever reported an increase in its pathogenicity, and no report has pointed to an increase in rates of hospitalization and fatality," said the center. "A recent animal study in Japan suggests that the pathogenicity of BQ.1.1(a lineage of BQ.1) is likely the same as or even lower than that of BA.5."“BQ.1虽然引起全球范围的关注，目前，未见任何国家报道BQ.1及其亚分支感染者的致病力增加，也无住院率和病死率增加的报道。近期日本的一项动物研究显示，BQ.1.1的致病性可能与BA.5相同或更低。”中国疾病预防控制中心指出。The center said that China will continue to ramp up surveillance of Omicron variants and promptly evaluate transmissibility, immunity evasiveness and virulence of new strains.该中心表示，我国将继续加强对奥密克戎变异株的基因组变异变迁监测，对新出现的传播优势毒株，及时开展传播力、免疫逃逸能力和致病力的评估。Because the virus is constantly mutating, the National Health Commission said on Tuesday that recovered COVID-19 patients are not immune to repeat infections.12月13日，国家卫生健康委员会表示，奥密克戎可能快速变异出新的亚分支，出现较强的免疫逃逸能力，康复者不能完全避免二次感染。"However, data from overseas has shown that the chance of getting infected with Omicron again within three to six months after the first bout is very low," the commission said.卫健委表示：“不过，国外有统计数据显示，感染过奥密克戎，不管有无症状，3至6个月内二次感染的概率相当低。”In addition, the commission said there is no definitive evidence supporting the theory that repeat infections can induce more serious clinical symptoms.此外，卫健委表示，目前没有定论认为重复感染会出现更严重的临床结果。"Based on observation of real-world cases, the proportion of patients who have suffered more serious health issues during a second infection is very low," the commission said. 卫健委表示，“目前病例来看，患者在重复感染时出现症状加重的倾向，这一比例非常低”。"The pathogenicity of Omicron has weakened, and the rate of severe cases is very low irrespective of being a first infection or repeat infection."“奥密克戎病毒致病力在减弱，不论是第一次感染，还是再感染，发生重症的概率都很低。”Zhong Nanshan, a prominent respiratory diseases expert, said during an interview last week that data from overseas has shown about 78 percent of patients who have recovered from Omicron infection won't catch the virus again for a lengthy period of time.著名呼吸系统疾病专家钟南山上周在接受采访时说，据国外资料显示，一旦感染过奥密克戎，不管有无症状，有78%的人在相当长时间内不会再重复感染。Pathogenicity英 [ˌpæθədʒeˈnɪsɪti] 美 [ˌpæθoʊdʒəˈnɪsɪti]n.致病性Virulence 英 [ˈvɪrələns] 美 [ˈvɪrələns]n.毒性bout英 [baʊt] 美 [baʊt]n.发作，发病期

Yes, we're still 'springing forward' and 'falling back' every year. But when it comes to human health, one of those time changes is way different than the other.

Dr. VanderWaal has been studying the dynamics of pathogens that spread through animal populations. As part of this episode, she discusses how virus classification has been implemented in the swine industry for the purpose of tracking proximate virus lineages and updating vaccination and biosecurity protocols to ensure that our industry stays ahead of the game.*Watch the full episode: https://www.swinecampus.com/blog-------------The Swine it Podcast Show is trusted and supported by innovative companies like:- Zinpro (https://zinpro.com/)- Gestal (http://jygatech.com/)- AB Vista (https://www.abvista.com/)- Adisseo (http://www.adisseo.com/)- Genesus (https://www.genesus.com/)- Evonik (https://animal-nutrition.evonik.com/en/species/swine/)- Cloudfarms (https://www.cloudfarms.com/)Give us a Rating & Review - http://getpodcast.reviews/id/1460280128

In this episode, Sharon R. Lewin, AO, FRACP, PhD, FAHMS, discusses what is known about the SARS-CoV-2 omicron variant, including:Transmissibility and infectiousness Immune evasionDisease severity Risks of hospitalization and death  Vaccine effectiveness  2- vs 3-dose vaccine effectivenessT-cell responsePresenter:  Sharon R. Lewin, AO, FRACP, PhD, FAHMSDirector, The Peter Doherty Institute for Infection and ImmunityProfessor of Infectious DiseasesUniversity of MelbourneConsultant Infectious Diseases PhysicianAlfred Hospital and Royal Melbourne HospitalMelbourne, AustraliaReview the downloadable slidesets at:https://bit.ly/32tp2BThttps://bit.ly/3JKyNLW Link to full program:https://bit.ly/3Ix8uZg  

The challenge of living with MS often begins with the challenge of getting a timely and accurate diagnosis. There are no symptoms, physical findings, or laboratory tests that can, by themselves, determine if someone has MS, and the most common symptoms of MS can often resemble symptoms of other conditions. All of these variables can sometimes lead to patients getting the wrong diagnosis. Dr. Andrew Solomon, Associate Professor of Neurological Sciences and Division Chief of Multiple Sclerosis at the University of Vermont Larner College of Medicine, is joining me to discuss diagnosing and misdiagnosing MS. We'll also fill you in on the details of the upcoming European MS Platform Annual Conference (it's free to register!). We'll tell you about a cannabis-based treatment that's been shown to improve spasticity without causing weakness in people with MS. We'll share the results of a study that looked at how a COVID-19 infection affects MS. You'll hear about newly published research that may have isolated the gene that causes male immune cells to drive more severe MS. And we'll give you the rundown of this month's Can Do MS programs. We have a lot to talk about! Are you ready for RealTalk MS??! European MS Platform Annual Conference  1:38 Cannabis extract improves spasticity without causing weakness  2:44 How COVID-19 may affect MS  4:43 A word about our show notes  6:49 Study shows male immune cells drive more severe MS  8:18 This month's Can Do MS programs  11:38 Dr. Andrew Solomon discusses diagnosing MS and misdiagnosing MS  13:13 Share this episode  25:54 Have a minute? Leave a rating & review for the podcast  26:14 SHARE THIS EPISODE OF REALTALK MS Just copy this link & paste it into your text or email: https://realtalkms.com/196 ADD YOUR VOICE TO THE CONVERSATION I've always thought about the RealTalk MS podcast as a conversation. And this is your opportunity to join the conversation by sharing your feedback, questions, and suggestions for topics that we can discuss in future podcast episodes. Please shoot me an email or call the RealTalk MS Listener Hotline and share your thoughts! Email: jon@realtalkms.comPhone: (310) 526-2283 And don't forget to join us in the RealTalk MS Facebook group! LINKS If your podcast app doesn't allow you to click on these links, you'll find them in the show notes in the RealTalk MS app or at www.RealTalkMS.com National MS Society COVID-19 Vaccine Guidance for People Living with MS European MS Platform Annual Conference STUDY: COVID-19 is Associated with New Symptoms of Multiple Sclerosis That are Prevented by Disease-Modifying Therapies STUDY: Male Sex Chromosomal Complement Exacerbates the Pathogenicity of Th17 Cells in a Chronic Model of Central Nervous System Autoimmunity Can Do MS Program Information and Registration Join the RealTalk MS Facebook Group Download the RealTalk MS App for iOS Download the RealTalk MS App for Android Give RealTalk MS a Rating and Review Follow RealTalk MS on Twitter, @RealTalkMS_jon, and subscribe to our newsletter at our website, RealTalkMS.com. RealTalk MS Episode 196 Guests: Dr. Andrew Solomon Tags: MS, MultipleSclerosis, MSResearch, MSSociety, RealTalkMS Privacy Policy

A genetic technique which could help improve predictions about the virulence of infectious bursal disease (IBDV) has identified pathogenicity in seven new strains of the virus which causes an immunosuppressive condition.

A genetic technique which could help improve predictions about the virulence of infectious bursal disease (IBDV) has identified pathogenicity in seven new strains of the virus which causes an immunosuppressive  condition. Isolates were collected from broiler and pullet flocks showing signs of the disease by Daral Jackwood, PhD, Professor at Ohio State University and his team, primarily from Pennsylvania and Ohio but with some in the Midwest, Southeast and California. 

Welcome back to USMLE Listen MICROBIOLOGY Chapter 2: In this episode we will go over some crucial USMLE exam-related facts on: 1-Bacterial Pathogenicity, Bacterial Genetics, and the different Toxins; We're going to group the exotoxins and endotoxins together on function, mode of action, and their role in disease. Furthermore, we will provide some USMLE questions and answer explanations! As always please email us at USMLElisten@gmail.com for your questions, anything you need to be cleared, or suggestions on how we can improve and initiate your auditory learning for the USMLE Step 1. Sources for USMLE LISTEN include First Aid, Osmosis, Uworld, and Kaplan study guides. This is Mark Labella, you can follow or message me on Instagram at markjlabella.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.06.372227v1?rss=1 Authors: Hassan, S. S., Pal Choudhury, P., Uversky, V. N., Dayhoff, G. W., Aljabali, A. A. A., Uhal, B., Lundstrom, K., Rezaei, N., Seyran, M., Pizzol, D., Adadi, P., Lal, A., Soares, A., Abd El-Aziz, T. M., Kandimalla, R., Tambuwala, M., Azad, G. K., Sherchan, S. P., Baetas-da-Cruz, W., Takayama, K., Serrano Aroca, A., Chauhan, G., Palu, G., Brufsky, A. Abstract: The coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) which is pandemic with an estimated fatality rate less than 1% is ongoing. SARS-CoV-2 accessory proteins ORF3a, ORF6, ORF7a, ORF7b, ORF8, and ORF10 with putative functions to manipulate host immune mechanisms such as interferons, immune signaling receptor NLRP3 (NOD-, LRR-, and pyrin domain-containing 3) inflammasome, inflammatory cytokines such as interleukin {beta} (IL-1{beta}) are critical in COVID-19 pathology. Outspread variations of each of the six accessory proteins of all complete proteomes (available as of October 26, 2020, in the National Center for Biotechnology Information depository) of SARS-CoV-2, were observed across six continents. Across all continents, the decreasing order of percentage of unique variations in the accessory proteins was found to be ORF3a>ORF8>ORF7a>ORF6>ORF10>ORF7b. The highest and lowest unique variations of ORF3a were observed in South America and Oceania, respectively. This finding suggests that the wide variations of accessory proteins seem to govern the pathogenicity of SARS-CoV-2, and consequently, certain propositions and recommendations can be made in the public interest. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.09.27.302927v1?rss=1 Authors: Won, D.-g., Lee, K. Abstract: Thanks to the improvement of New Generation Sequencing (NGS), genome-based diagnosis for rare disease patients become possible. However, accurate interpretation of human variants requires massive amount of knowledge gathered from previous researches and clinical cases. Also, manual analysis for each variant in the genome of patients takes enormous time and effort of clinical experts and medical doctors. Therefore, to reduce the cost of diagnosis, various computational tools have been developed for the pathogenicity prediction of human variants. Nevertheless, there has been the circularity problem of conventional tools, which leads to the overlap of training data and eventually causes overfitting of algorithms. In this research, we developed a pathogenicity predictor, named as 3Cnet, using deep recurrent neural networks which analyzes the amino-acid context of a missense mutation. 3Cnet utilizes knowledge transfer of evolutionary conservation to train insufficient clinical data without overfitting. The performance comparison clearly shows that 3Cnet can find the true disease-causing variant from a large number of missense variants in the genome of a patient with higher sensitivity (recall = 13.9 %) compared to other prediction tools such as REVEL (recall = 7.5 %) or PrimateAI (recall = 6.4 %). Consequently, 3Cnet can improve the diagnostic rate for patients and discover novel pathogenic variants with high probability. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.13.248575v1?rss=1 Authors: Park, J. J., Chen, S. Abstract: The COVID-19 pandemic caused by SARS-CoV-2 has become a major threat across the globe. Here, we developed machine learning approaches to identify key pathogenic regions in coronavirus genomes. We trained and evaluated 7,562,625 models on 3,665 genomes including SARS-CoV-2, MERS-CoV, SARS-CoV and other coronaviruses of human and animal origins to return quantitative and biologically interpretable signatures at nucleotide and amino acid resolutions. We identified hotspots across the SARS-CoV-2 genome including previously unappreciated features in spike, RdRp and other proteins. Finally, we integrated pathogenicity genomic profiles with B cell and T cell epitope predictions for enrichment of sequence targets to help guide vaccine development. These results provide a systematic map of predicted pathogenicity in SARS-CoV-2 that incorporates sequence, structural and immunological features, providing an unbiased collection of genetic elements for functional studies. This metavirome-based framework can also be applied for rapid characterization of new coronavirus strains or emerging pathogenic viruses. Copy rights belong to original authors. Visit the link for more info

Nels and Vincent continue their discussion of SARS-CoV-2 from an evolutionary viewpoint, including function of the furin cleavage site, whether Vervet cells are an informative system, another bat isolate, and a nomenclature to assist genomic epidemiology. Hosts: Nels Elde and Vincent Racaniello Subscribe (free): iTunes, Google Podcasts, RSS, email Become a patron of TWiEVO SARS-CoV-2 in Vero cells (bioRxiv) More related SARSr virus from bat (bioRxiv) Patient isolates in Vero cells (medRxiv) Nomenclature for genomic epidemiology (bioRxiv) Time stamps by Jolene. Thanks! Science Picks Nels - EvoEco seminars Vincent - Coronavirus book for children Music on TWiEVO is performed by Trampled by Turtles Send your evolution questions and comments to twievo@microbe.tv

The TWiM team explore how Lactobacillus reuteri can rescue social deficits in three mouse models of autism spectrum disorder, and the role of Salmonella persisters in undermining host defenses during antibiotic treatment. Subscribe to TWiM (free) on iTunes, Google Podcasts, Stitcher, Android, RSS, or by email.  Become a Patron of TWiM! Please take the TWiM listener surveyBacteria alter behavior in mouse autism models (Neuron) Mice behaving badly (TWiM 131) Salmonella persisters undermine host immune defenses (Science) Persister cells (Ann Rev Microbiol) Music used on TWiM is composed and performed by Ronald Jenkees and used with permission. Send your microbiology questions and comments to twim@microbe.tv

Dr Amit Khera:                  Welcome to Circulation on the Run, your weekly summary and backstage pass to the journal. I'm Dr Amit Khera, associate editor and digital strategies editor from UT Southwestern Medical Center in Dallas. And I have the privilege of standing in for Dr Carolyn Lam, your usual weekly podcast host. Today we have a special treat. It is our semiannual fellows and training FIT podcast. And the additional part of this treat is we have three very special FITs today. These are our assistant editors for social media for Circulation. And really I want to introduce you just a moment, but I want to thank these three for their hard work and efforts. It really is them that helped bring our social media to life. And importantly for us, we really have a commitment to enhancing fellow education involving fellows in our editorial process and really making sure that the journal is appealing to fellows in training. So we really rely on these three to help us understand what best resonates and what is most helpful for fellows in training. So without further ado, Jainy Savla from UT Southwestern. Welcome Jainy. Jainy Savla:                         Thanks for having me on the podcast today. Dr Amit Khera:                  And we have Daniel Ambinder from Johns Hopkins University. Hi Dan. Daniel Ambinder:             Hey Amit. Thanks for having me on the podcast today. Dr Amit Khera:                  Absolutely. And finally we have Jeff Hsu from UCLA. Hi Jeff. Jeff Hsu:                               Hi Amit and hi everyone. Very glad to be here. Dr Amit Khera:                  Well, Jainy, I'm going to start with you. You've been with us on the social media side the longest. I think it's maybe almost a year or a bit more that you've been working on these efforts. And again, very much appreciate all of your hard work and insight. Tell us a bit about yourself. Jainy Savla:                         So I'm currently a research fellow at UT Southwestern. So I completed my general cardiology training and I've been doing some extra research training in one of our basic science labs there. Dr Amit Khera:                  So not surprisingly with your background, do you select an article? So we've asked them each to select one article as they've been working through the social media side and see all of our articles come through. Each to select one that they found was interesting and perhaps summarize for us what it included and what appealed to them. So Jainy, tell us a little bit about the article you chose and why you chose it. Jainy Savla:                         So, I chose one of the articles that was published in April of 2018 from the Molkentin team lab. And this is a basic science article that focused on which types of cells contribute to heart regeneration. They hadn't thought that there was cardiac progenitor cell that could contribute to the development of new cardiomyocytes. And more recent data has shown that maybe that's not quite the case. So what this study did was used a lot of fancy lineage tracing models to try to figure out which types of cells we're actually contributing to the development of new cardiomyocytes. So importantly, what came from this was that one of their models, they were able to delete two transcription factors that are necessary for cardiomyocytes to develop from these progenitor cells. But they found that when they did that, they even got a higher number of cardiomyocytes that formed. And then what they were able to show in this paper was that actually comes from fusion of leukocytes to cardiomyocytes. And then interestingly, they found a role for one of these transcription factors and the development of endothelial cells. So that was kind of a new, not known function of one of these genes that was previously thought to be just contributory to cardiac development. Dr Amit Khera:                  It's really a fascinating article when you think about it. Most of the science we publish are people bringing to light new discoveries and certainly there was a component of that here. But in many ways, it was kind of a different article where there had been this a prevailing thought about these c kit positive cells and here they're actually had gone through, refuted what people had thought was happening with these in this de novo cardiomyocyte formation. So you'll see that very often where people's articles or work is headed out to sort of maybe refute or set right what's happening in the literature in the field. Can you comment on that as to that type of article and how that appealed to you in this study? Jainy Savla:                         That is interesting because previously it has meant that these cells can be used as a therapeutic option in human patients. But some of them were recent data showed that perhaps the new cardiomyocytes weren't actually coming from these cells, but it was hard to say. So the nice part about this paper was really they used a lot of important lineage tracing models to really show where these cells are coming from. And it helped clarify some of the, I guess, more confusing science that had been in the field since there were a few papers that showed these cells were contributary and then a few papers that have shown that maybe they weren't. So I think that's really helpful, particularly when you're talking about things that could be potentially used as therapeutic agents in human. And also the interesting thing is that while these cells themselves may not be useful to perhaps harvest and give to someone, you could potentially alter these cells and then they produce cells that fuse with cardiomyocytes. Or could you use this a different way? So I thought that was also interesting about this article. Dr Amit Khera:                  Great points in it. It does remind us again that in our enthusiasm for rushing things to clinical practices in some things in this field, the importance of rigorous basic science to really understand the molecular underpinnings. And as you mentioned, there's some new insights here that could be used for clinical therapeutic purposes in the future. So definitely an interesting article and glad you enjoyed it and brought it to our attention. I'm going to ask you a bit of a different question. You again have been working with this in the social media side for longer. You've seen this now for some time about the different articles that come through. I know you and I've had several conversations about our different platforms, Twitter or Facebook, and how they're different and how we engage with them and how we engage with the audience. Can you tell us a little bit just reflecting now on your time and working with social media from a journal perspective, kind of what you've learned? What are some interesting observations over this year? Jainy Savla:                         Definitely one interesting observation is just that their general usage of these social media platforms has increased significantly since I've started doing this. And you can see this with when we get articles that are accepted, how many authors have Twitter handles that they'd like to be tagged in some of these posts. And that's just gone up significantly since I've started doing this. And that also changes sort of what the comments we get on some of the posts and the back and forth discussions that we're seeing on these platforms. And then the second thing I found really interesting over time is that the way people use Facebook is really different from the way people use Twitter. And you can follow the discussions that people have linked to our posts a little bit better on Facebook. And then on Twitter, there's also a lot of similar discussions about these posts. But they kind of manifest in different ways and it's really interesting to see how that plays out. Dr Amit Khera:                  I think those are fantastic points. And from a fellow's perspective, how do you think fellows are engaging with social media now compared to maybe, I don't know, when you started your training a few years back. What have you seen in a positive light? Jainy Savla:                         I mean in general, there are more fellows on Twitter now than when I was a first-year fellow. Even myself, I've got my Twitter account when I was in fellowship. I didn't have one prior to that. I mean it's interesting because people are able to showcase their work a little bit better I think with these types of handles whereas before maybe you wouldn't know that even one of your own co fellows had published something. So it's kind of nice to see people use that kind of as a networking tool in some ways or to showcase some of their own work, which is something that when I was a first year and I didn't have a Twitter handle and there weren't as many fellows on Twitter, I didn't really notice some of the work that's being done by some of my colleagues at my level. Dr Amit Khera:                  Those are great points and I'll stoplight some of the things you just said talking about it being a way for fellows to really showcase their work, to help with networking and in some ways, it's sort of the great equalizer. So I think it's really a valuable platform specifically for fellows. Well thank you Jainy. I'm going to move on to Daniel and hear a little bit from Daniel. Tell us a bit about yourself. Daniel Ambinder:             I'm currently a second year cardiology fellow at John's Hopkins Hospital and I plan on doing interventional and structural cardiology in the future. Dr Amit Khera:                  Great and certainly a lively and growing field and so many exciting things happening. Well, it's interesting you chose an article today that is more of a clinical article and obviously quite different than the last one we heard, but equally as interesting. Tell us a little about the article you've chose and why you chose it. Daniel Ambinder:             I was very excited about this article that was published in Circulation back in July 2018. So, it's by Dr Borlaug and Reddy on how to diagnose HFpEF and what they did was they took patients with clinical dyspnea and they used invasive human dynamics to kind of assess whether or not they had HFpEF. And by doing so they were able to generate a list of clinical and eco based guidance to help us kind of identify patients with heart failure with preserved ejection fraction. So they came up with this amazing little table which was featured in Circulation and on Circulation twitter, where they have a chart that basically goes through several clinical variables including weight and hypertensiveness, atrial fibrillation, pulmonary hypertension, being elderly. And filling pressure is based on echo cardiographic information. And by that they were able to generate a score and give you a probability of if your patient has HFpEF or not.                                                 And the reason why I really enjoyed reading this article and also posting this article was because going through internal medicine and not being so fundamentally aware of echo and kind of what goes into understanding left ventricular filling pressures, it was challenging to make a diagnosis of heart failure with preserved ejection fraction. Do you just basically say, "My patient has lower extremity swelling but normal EF? They have heart failure with preserved ejection fraction and [inaudible 00:09:32] on the [inaudible 00:09:33]. And so I thought that this would be really helpful to the medical community at large. And in fact, shortly after we posted it, I saw that our cardiology console fellow is actually utilizing this exact table to help one of the medicine teams manage a patient with lower extremity swelling and come to the diagnosis of heart failure with preserved ejection fraction. So that is why I chose this article for today. Dr Amit Khera:                  That's a great article and I thought you summarized it very well. And it is a field. HFpEF you'd see a lot of articles in Circulation on this topic. We have many people that are interested from an editor’s level but also from a society level. This is a huge problem, but we know very, very little. And I'm sure you know that as well and this was a wonderful tool. Just shows you're sort of the beauty and simplicity. Although if you read it, the message were pretty rigorous and they had a lot of great work that they did to develop it. But I love that the H2 HFpEF, how they basically came up with it h for heavy and the f from fibrillation. So I thought that was incredibly creative and a very simplistic but useful score. So, you said your, tell us about yourself. Have you used the H2 of the HFpEF score yet? Daniel Ambinder:             Absolutely. I use it in clinic on a daily basis. And I actually pull up the Tweet in my office and show the patients why I think that they have heart failure preserved ejection fraction, especially since many of my patients start to get really nervous when you start talking about heart failure. But then they don't understand that they have a normal functioning heart. They can't really put those two together. And so going through this chart and going through the etiology, or at least what we know about heart failure with preserved ejection fraction, turns out to be quite helpful. Dr Amit Khera:                  And the basis of this study goes back to hemodynamics. This obviously is a cohort where they had done invasive hemodynamics to essentially diagnosed HFpEF based on pressure. So as you, as someone who's going interventional and structural where we are really seeing kind of the rebirth or refocus on hemodynamics again, tell me a little bit like what you're learning in terms of hemodynamics and how you think that importance in today's practice of cardiovascular medicine. Daniel Ambinder:             One of my passions is spending as much time as I possibly can in the cardiac ICU. And we're fortunate to meet many different patients that come in with very different kinds of cardiogenic shock for other hemodynamic compromise from other types of shock. And I have found it extremely helpful to think about either using a virtual Swan or by actually getting the measurements with a PA catheter to kind of identify where the break in the system is to hopefully provide our patients with the ability to turn them around in a fast manner before they develop metabolic compromise from prolonged hypoperfusion. Dr Amit Khera:                  Great summary of how you're using hemodynamics and the training. And I'm going to pivot. The last question for you is when we first met I think several months back and we're communicating about your interest in social media, one thing that was really interesting and fascinating was the great work you're doing on Twitter on your own account where you essentially, if I think you told me this right, you sit on your iPhone and basically in this matter of a very few minutes would construct cases and teaching points on Twitter. So tell me a little bit about that, about using Twitter for medical education and learning cardiology and cases. And I know you're passionate about that. So tell us a little bit more about that. Daniel Ambinder:             Back in May, last year, I had been in my first year of cardiology fellowship. And I was really kind of obsessed with grabbing as much imaging and cases as I could to construct them into teaching stories to share these important stories that I encounter with other people. And so also share the aha moments that I have when I'm learning from my mentors about a new clinical condition or even a clinical condition that I've encountered many times. We never thought about any unique way. And so I was putting these all together and developing somewhat of a library of cases. But I would share them with the residents that I was working with at the time. And then Dr Erin Michos was one of my mentors at Hopkins. She's an echocardiographer and she kind of exposed me to the Twitter community where you're really able to just start reaching out to different people and share the same insights that I had saved on my drive on my computer. And so I started constructing these cases, putting that together and developing them and then associating them with like a few bullet pointed tidbits of pearls that I can put on Twitter. And I quickly realized what an amazing community Twitter have to offer in terms of cardiology and in terms of the medical education community at large.                                                 At first, I realized you can't put out content and not expect to participate in a conversation. It has to be two ways. You have to really engage with others and others will engage with you. And then just a couple months later, it's really grown that you can post a case, post the teaching pearl and in about 24 hours it can be viewed thousands and thousands of times, really internationally. And generates just so much great conversation. So it's been really a tremendous way to communicate with the world, especially within the cardiovascular world. Dr Amit Khera:                  Well thanks. I think there's so much learning that can happen and I think the work you're doing with cases and with others. And I know when I've gone on Twitter, even in just two minutes you can see really fascinating things and learn a lot. So keep up the good work and appreciate your efforts there. I'm going to switch gears and finally finished with Jeff Hsu from UCLA. Jeff, tell us a bit about yourself. Jeff Hsu:                               I'm a fellow at UCLA. So I actually finished my general cardiology fellowship pretty recently and now I'm a research fellow in the STAR program here. I'm also enrolled in the PhD program at UCLA in the Department of Physiology and planning to defend in the next few months. So right now, very stressed out about that. Starting in July, I'll be starting advanced fellowship in advanced heart failure and transplant here at UCLA.                                                 Well excellent and best of luck to you in your PhD defense. Now you also chose a very interesting article that again, all of yours are a bit different. So tell us a little about the article you chose and why you chose it.                                                 When I chose this article, I was really excited by a few weeks ago. It was published in the December 4th issue of Circulation called Determining the Pathogenicity of a Genomic Variant of Uncertain Significance Using CRISPR/Cas9 and Human Induced Pluripotent Stem Cells. So this came out of the lab of Joe Wu at Stanford and the co first authors is Ning Ma, Joe Zhang and Ilanit Itzhaki. But I think the beauty of this article is that it really addressed this frustrating clinical scenario in question that we often encounter nowadays in this era of genome sequencing. And now that we're sequencing a lot more people, since the cost of sequencing has come down a lot, we were finding a lot of these mutations that we don't know what to do with, so I think Dr Wu's lab really try to address this question using the disease model with the cardiomyopathy. So, leveraging Dr Wu's expertise in using human induced pluripotent stem cells or iPSCs, they found a patient who is actually healthy but apparently had this mutation in this gene called MYL3 or myosin light chain 3. And so this patient had a variance of uncertain significance in this gene.                                                 Now, notably, this patient, again had no clinical phenotype, was very healthy and the patient's family members over three generations were all healthy too. But had this mutation that based on in silico analyses was thought to be likely pathogenic. So using cells from this patient that they reprogrammed into cardiomyocyte, they tested various properties of these cells from the same patient to see whether or not they thought this mutation is actually a pathogenic mutation. So again, using these reprogrammed cardiomyocytes, they tested a variety of things including gene expression, sarcomere structure, and cell contractility, action potentials, and the handling of calcium. And they saw that even with this mutation, there were no abnormal findings in vitro in their system.                                                 Now just to prove that their cell culture system and this in vitro model of testing the pathogenicity of certain mutations actually works, they actually took cells from a patient who did have the clinical phenotype as a result of a known mutation that causes hypertrophic cardiomyopathy. And found that when testing those cells in vitro, they did demonstrate abnormal phenotypes in all the parameters I mentioned before. So I thought this is really exciting. I thought this is a great way to address, potentially answer whether or not we think these variants of uncertain significance that we often encounter are indeed pathogenic because we are often just left in this situation where we don't know what to do with this information. But this potentially at least is a proof of concept for this protocol where we can finally take advantage of the ability to take cells from our patient and actually test them in the lab to see whether or not either various treatments work or whether or not these mutations that actually will results in pathology down the line. So I thought overall this was a great paper that was a great summary of how we can take the bedside to the bench actually. And I'm just really looking forward to the future where we can maybe then bring it back to the bedside. Dr Amit Khera:                  Well thanks. I think that's an excellent choice and a great summary. And this article really hit all of the kind of timely and cutting-edge topics in the era genomic medicine and precision medicine have really kind of individualized treatments. And when we get stuck, these VUSes, these are a nightmare. And also this is sort of proof of concept for extending this to other treatments and other ways to test drugs and therapies. I've heard Joe, we talk about this before and use the word disease in the dishes. He did I think in the article itself and it's exactly that. I mean the potential here is profound. I'll pivot this into the next question for you. For our roles, one thing we do is we interact a lot with media and I interact a lot with them to help translate, I guess, the articles that we have to things that would be able to be digestible for media and for lay individuals. It was interesting because it's hard for us to do that with basic science and most of the time we have some difficulty in translating that. But this one translated pretty well and I think we had done some various press releases and things because it really showed the potential of modern medicine and kind of the excitement of it.                                                 But that gets to the question I have for you, something we have discussed as well, your interest in basic science and some of the challenges of taking basic science articles and digesting them down to a couple hundred-word tweet. Even as beautiful as all the pictures are, and in this article I think there's six figures, but each panel is 10 pictures or 10 figures by themselves. And how do we digest basic science articles down to make them really appeal to people on social media and help people understand that may not be in the fields or in basic science that are clinicians, if you will. I know you've thought about that a little bit. Tell me a little bit about your thoughts on that. Jeff Hsu:                               Jainy, Dan and I have this challenge on a weekly basis, figuring out how to summarize great articles such as this one into a short tweet. And I think that is a big challenge particularly for basic science articles on social media to make it appeal to a broader audience because the audience you're seeing on Twitter and Facebook, again, they're not just basic scientists. If you want to catch people's attention, you need to find a way to really understand the big picture of the question you're answering in your basic science research. So I think that is a challenge. You're challenged to make your science appealing to a broader audience. But I think again, that's one of the advantages of social media is that you can appeal to a larger audience and have a wide range of people engage with your research and understand your research. So it is something that we work on is to try to pick out the figure that best represents the science that was done in these basic science articles.                                                 It can be quite challenging because a lot of times one picture won't do it justice. So it's tough to distill a full article in one picture. It is helpful when some articles do have a summary, a graphic or figure where they typically reserve their last figure for either a cartoon or some type of schematic that really explains either the mechanism or pathway that they explored in their article. So what we've found is that these articles that do have some of these illustrations or summary figures, they seem to engage a larger audience on Twitter and social media. So personally I find it more appealing when I do see these summary figures. So if there is one recommendation, I would have the basic science researchers, especially trainees is in this age of social media, try to come up with an illustration or summary figure for your research. I think it helps you figure out what is truly important with the research that you've done and helps you communicate this research to a broader audience. And I've seen a lot of people take advantage of a graphic designers to really help them illustrate their research. And I found that to be very effective in articles I've read on social media. Dr Amit Khera:                  Thanks Jeff. That's a great point and great suggestion. And certainly these days the most effective communicators are those they can translate their complex science into easily digestible bites and can think of ways to portray them in ways that sort of summarize, like you said, be it summary figures or otherwise. And it's a challenge and also talent. And you all are certainly perfecting that. Well, I think we've had an excellent conversation. I have to tell you, I'm so excited to get the chance to spotlight you all. You do excellent work each day. Every week you're working hard and coming up with great ideas and suggestions and we really value having your input as fellows and training and as a colleague.                                                 Thank you for joining us today on our FIT podcast. Amit Khera standing in for Carolyn Lam. We look forward to seeing you for our next edition of Circulation on the Run. This program is copyright American Heart Association 2018.  

What is the difference between infectivity, pathogenicity, and virulence? Why does it matter? Listen and learn why we need to know each of these for every pathogen. 

Professor Peter Simmonds studies the epidemiology, evolution and emergence of a wide range of human pathogenic viruses. RNA viruses are major pathogens that represent the majority of new viruses emerging over time. They are particularly good at evading the host's response to infection. A better understanding of the interaction between virus and host can lead to a better control of viral infections. Recent discoveries on viral genome composition and structure might allow us to manipulate this interaction and generate new, safer vaccines.

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler The TWiVsters explore mutations in the interferon pathway associated with severe influenza in a child, outbreaks of avian influenza in North American poultry farms, Ebolavirus infection of the eye weeks after recovery, and Ebolavirus stability on surfaces and fluids. This episode is sponsored by @ASM Conferences and ASM Microbe Links for this episode Life threatening influenza and IRF7 deficiency (Science) Whole exome sequencing (Wikipedia) Herpes encephalitis in children with Trif deficiency (TWiV 175) Avian influenza in the US (USDA, ProMedMail, CDC) Ebola eye (NEJM, NYTimes) Viral persistence (Virology lectures, pdf) Uveitis (National Eye Institute) Image credit Stability of Ebolavirus on surfaces (EID) Ignorance with Stuart Firestein (TWiV Special) Letters read on TWiV Timestamps by Jennifer. Thank you! Weekly Science Picks Alan - Winogradsky time-lapseRich - Missing link in evolution of complex cellsKathy - GrantomeDickson - National Geographic Landscape Photo of the DayVincent - PyMol and Chimera Listener Pick of the Week Mauricio - Vax!

Eshwar Mahenthiralingam Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, UK speaks on "Burkholderia bacteria: using genetics to balance pathogenicity with biotechnological versatility."This seminar has been recorded by ICGEB Trieste

Background: Toxigenic Corynebacterium ulcerans can cause a diphtheria-like illness in humans and have been found in domestic animals, which were suspected to serve as reservoirs for a zoonotic transmission. Additionally, toxigenic C. ulcerans were reported to take over the leading role in causing diphtheria in the last years in many industrialized countries. Methods: To gain deeper insights into the tox gene locus and to understand the transmission pathway in detail, we analyzed nine isolates derived from human patients and their domestic animals applying next generation sequencing and comparative genomics. Results: We provide molecular evidence for zoonotic transmission of C. ulcerans in four cases and demonstrate the superior resolution of next generation sequencing compared to multi-locus sequence typing for epidemiologic research. Additionally, we provide evidence that the virulence of C. ulcerans can change rapidly by acquisition of novel virulence genes. This mechanism is exemplified by an isolate which acquired a prophage not present in the corresponding isolate from the domestic animal. This prophage contains a putative novel virulence factor, which shares high identity with the RhuM virulence factor from Salmonella enterica but which is unknown in Corynebacteria so far. Furthermore, we identified a putative pathogenicity island for C. ulcerans bearing a diphtheria toxin gene. Conclusion: The novel putative diphtheria toxin pathogenicity island could provide a new and alternative pathway for Corynebacteria to acquire a functional diphtheria toxin-encoding gene by horizontal gene transfer, distinct from the previously well characterized phage infection model. The novel transmission pathway might explain the unexpectedly high number of toxigenic C. ulcerans.

Background: Ralstonia solanacearum is a soil-borne beta-proteobacterium that causes bacterial wilt disease in many food crops and is a major problem for agriculture in intertropical regions. R. solanacearum is a heterogeneous species, both phenotypically and genetically, and is considered as a species complex. Pathogenicity of R. solanacearum relies on the Type III secretion system that injects Type III effector (T3E) proteins into plant cells. T3E collectively perturb host cell processes and modulate plant immunity to enable bacterial infection. Results: We provide the catalogue of T3E in the R. solanacearum species complex, as well as candidates in newly sequenced strains. 94 T3E orthologous groups were defined on phylogenetic bases and ordered using a uniform nomenclature. This curated T3E catalog is available on a public website and a bioinformatic pipeline has been designed to rapidly predict T3E genes in newly sequenced strains. Systematical analyses were performed to detect lateral T3E gene transfer events and identify T3E genes under positive selection. Our analyses also pinpoint the RipF translocon proteins as major discriminating determinants among the phylogenetic lineages. Conclusions: Establishment of T3E repertoires in strains representatives of the R. solanacearum biodiversity allowed determining a set of 22 T3E present in all the strains but provided no clues on host specificity determinants. The definition of a standardized nomenclature and the optimization of predictive tools will pave the way to understanding how variation of these repertoires is correlated to the diversification of this species complex and how they contribute to the different strain pathotypes.

The NF-kappa B/REL-family of transcription factors plays a central role in coordinating the expression of a wide variety of genes controlling immune responses including autoimmunity of the central nervous system (CNS). The inactive form of NF-kappa B consists of a heterodimer which is complexed with its inhibitor, I kappa B. Conditional knockout-mice for I kappa B alpha in myeloid cells (IysMCreI kappa B alpha(fl/fl)) have been generated and are characterized by a constitutive activation of NF-kappa B proteins allowing the study of this transcription factor in myelin-oligodendrocyte-glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), a well established experimental model for autoimmune demyelination of the CNS. In comparison to controls, IysMCreI kappa B alpha(fl/fl) mice developed a more severe clinical course of EAE. Upon histological analysis on day 15 p.i., there was an over two fold increased infiltration of T-cells and macrophages/microglia. In addition, IysMCreI kappa B alpha(fl/fl) mice displayed an increased expression of the NF-kappa B dependent factor inducible nitric oxide synthase in inflamed lesions. These changes in the CNS are associated with increased numbers of CD11b positive splenocytes and a higher expression of Ly6c on monocytes in the periphery. Well in accordance with these changes in the myeloid cell compartment, there was an increased production of the monocyte cytokines interleukin(IL)-12 p70, IL-6 and IL-1beta in splenocytes. In contrast, production of the T-cell associated cytokines interferon gamma (IFN-gamma) and IL-17 was not influenced. In summary, myeloid cell derived NF-kappa B plays a crucial role in autoimmune inflammation of the CNS and drives a pathogenic role of monocytes and macrophages independently from T-cells.

Infection with Helicobacter pylori, carrying a functional cag type IV secretion system (cag-T4SS) to inject the Cytotoxin associated antigen (CagA) into gastric cells, is associated with an increased risk for severe gastric diseases in humans. Here we studied the pathomechanism of H. pylori and the role of the cag-pathogenicity island (cag-PAI) for the induction of gastric ulcer and precancerous conditions over time (2-64 weeks) using the Mongolian gerbil model. Animals were challenged with H. pylori B128 (WT), or an isogenic B128DeltacagY mutant-strain that produces CagA, but is unable to translocate it into gastric cells. H. pylori colonization density was quantified in antrum and corpus mucosa separately. Paraffin sections were graded for inflammation and histological changes verified by immunohistochemistry. Physiological and inflammatory markers were quantitated by RIA and RT-PCR, respectively. An early cag-T4SS-dependent inflammation of the corpus mucosa (4-8 weeks) occurred only in WT-infected animals, resulting in a severe active and chronic gastritis with a significant increase of proinflammatory cytokines, mucous gland metaplasia, and atrophy of the parietal cells. At late time points only WT-infected animals developed hypochlorhydria and hypergastrinemia in parallel to gastric ulcers, gastritis cystica profunda, and focal dysplasia. The early cag-PAI-dependent immunological response triggers later physiological and histopathological alterations towards gastric malignancies.

Background: Photorhabdus luminescens and Yersinia enterocolitica are both enteric bacteria which are associated with insects. P. luminescens lives in symbiosis with soil nematodes and is highly pathogenic towards insects but not to humans. In contrast, Y. enterocolitica is widely found in the environment and mainly known to cause gastroenteritis in men, but has only recently been shown to be also toxic for insects. It is expected that both pathogens share an overlap of genetic determinants that play a role within the insect host. Results: A selective genome comparison was applied. Proteins belonging to the class of two-component regulatory systems, quorum sensing, universal stress proteins, and c-di-GMP signalling have been analysed. The interorganismic synopsis of selected regulatory systems uncovered common and distinct signalling mechanisms of both pathogens used for perception of signals within the insect host. Particularly, a new class of LuxR-like regulators was identified, which might be involved in detecting insect-specific molecules. In addition, the genetic overlap unravelled a two-component system that is unique for the genera Photorhabdus and Yersinia and is therefore suggested to play a major role in the pathogen-insect relationship. Our analysis also highlights factors of both pathogens that are expressed at low temperatures as encountered in insects in contrast to higher (body) temperature, providing evidence that temperature is a yet under-investigated environmental signal for bacterial adaptation to various hosts. Common degradative metabolic pathways are described that might be used to explore nutrients within the insect gut or hemolymph, thus enabling the proliferation of P. luminescens and Y. enterocolitica in their invertebrate hosts. A strikingly higher number of genes encoding insecticidal toxins and other virulence factors in P. luminescens compared to Y. enterocolitica correlates with the higher virulence of P. luminescens towards insects, and suggests a putative broader insect host spectrum of this pathogen. Conclusion: A set of factors shared by the two pathogens was identified including those that are involved in the host infection process, in persistence within the insect, or in host exploitation. Some of them might have been selected during the association with insects and then adapted to pathogenesis in mammalian hosts.

Wed, 13 Jun 2007 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/8057/ https://edoc.ub.uni-muenchen.de/8057/1/Antonenka_Uladzimir.pdf Antonenka, Uladzimir ddc:500, ddc:570, Fakultät für

In dieser Arbeit wurde die Methode der subtraktiven Hybridisierung angewandt, um neue Virulenzfaktoren zu finden, die spezifisch für hochpathogene Yersinia enterocolitica Stämme sind. Hierfür wurde die DNA eines nicht pathogenen „Treiber”-Stammes (Y. enterocolitica NF-O, Biotyp 1A) gegen die DNA eines hochpathogenen „Tester”-Stammes (Y. enterocolitica WA-314, Biotyp 1B) subtrahiert. Mit Hilfe der subtraktiven Hybridisierung konnten verschiedene Tester-spezifische Sequenzen ermittelt werden, die sowohl für bereits bekannte als auch neue potentielle Virulenzmarker kodieren. In dieser Arbeit konnte ein neues TypII-Sekretionscluster, genannt yts1 (Yersinia TypII Sekretion 1), ermittelt werden. Das yts1-Gencluster umfasst ein 13 kb großes Operon-ähnliches Modul, welches die Gene yts1C-S enthält. Mittels reverser Transkription/PCR konnte eine bevorzugte Transkription bei 37 °C gezeigt werden. Southern Blot-Analysen sowie PCR haben gezeigt, dass das yts1-Gencluster nur in den hochpathogenen Y. enterocolitica Stämmen vorkommt. Dagegen sind yts1-Gene weder in schwachpathogenen sowie apathogenen Y. enterocolitica Stämmen noch in Y. pseudotuberculosis- und Y. pestis-Isolaten zu finden. Durch Inaktivierung des yts1E-Gens in Y. enterocolitica wurde eine Mutante hergestellt und hinsichtlich Mauspathogenität mit dem Mutterstamm verglichen. Bei oraler Infektion der Mäuse erwies sich die yts1E-Mutante als attenuiert (geringere Keimzahlen) in Leber und Milz im Vergleich zum Mutterstamm. Im Gegensatz dazu konnte bei intravenöser Infektion der Mäuse kein Unterschied zwischen Mutante und Mutterstamm festgestellt werden. Dies könnte ein Hinweis darauf sein, dass das TypII-Sekretionssystem die Erregerdissemination von den Peyer-Plaques in Milz and Leber fördert. Das yts1-Sekretionscluster grenzt stromabwärts an ein Gen, welches für ein potentielles Chitin-Bindungsprotein (ChiY) kodiert. ChiY ist ein mögliches Substrat des Yts1-Sekretons. Sequenzanalysen sagen voraus, dass ChiY ein 55-kDa Protein mit zwei definierten Chitin-Bindungsdomänen ist, von denen sich die eine Domäne am N- und die andere am C-Terminus des Proteins befindet. Es konnte gezeigt werden, dass rekombinantes ChiY Chitin bindet. Sequenzanalysen des zugänglichen fast kompletten Genoms von Y. enterocolitica 8081 (Biotyp 1B) führten zum Nachweis eines möglichen zweiten TypII-Sekretionscluster, das in dieser Arbeit als yts2 bezeichnet wird. Wie mittels PCR gezeigt werden konnte, kommt yts2 - im Gegensatz zu Y. pseudotuberculosis und Y. pestis - in allen getesteten pathogenen und apathogenen Y. enterocolitica-Stämmen vor. Reverse Transkriptionsanalysen/PCR zeigten, dass die yts2 - Gene bevorzugt bei 27 °C abgelesen werden. Mittels subtraktiver Technik konnte auch ein neues Insertionselement (IS1330) charakterisiert werden. Durch Southern Blot-Analysen konnte gezeigt werden, dass IS1330 nur in pathogenen Y. enterocolitica Serotypen vorkommt und somit für die epidemiologische Typisierung dieser Spezies eingesetzt werden kann. Diese Arbeit repräsentiert einen neuen Ansatz zur Aufklärung von unterschiedlichen intraspezifischen Genomsequenzen von Y. enterocolitica mit Hilfe der subtraktiven Hybridisierung, um unser Verständnis der genetischen Vielfalt und Heterogenität dieser bakteriellen Spezies zu erweitern. Das zum ersten Mal hier beschriebene yts1-Cluster repräsentiert einen neuen Lokus, der eine wichtige Rolle für die Pathogenese der hochpathogenen Y. enterocolitica Stämme spielt.