Podcasts about Clonal

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Best podcasts about Clonal

Latest podcast episodes about Clonal

Blood Podcast
First-line asciminib for chronic myeloid leukemia, a new risk score for clonal cytopenia, and genotyped D-positive blood transfusion in sickle cell anemia

Blood Podcast

Play Episode Listen Later Nov 7, 2024 21:19


In this week's episode we'll learn more about the ASCEND study, which investigated first-line asciminib in chronic phase chronic myeloid leukemia; a new risk score for myeloid neoplasm transformation in patients with clonal cytopenia of undetermined significance; and use of RHD genotyped D-positive blood transfusions in patients with sickle cell and unexpected anti-D antibodies.Featured ArticlesAsciminib Monotherapy as Frontline Treatment of Chronic Phase Chronic Myeloid Leukaemia - Results from the ASCEND StudyRisk Prediction for Clonal Cytopenia: Multicenter Real-World Evidence Genotyped RhD+ red cells for D-positive patients with sickle cell disease with conventional RHD and unexpected anti-D 

Best of Oncology Podcast Series
Navigating AML: Unraveling FLT3 Clonal Evolution For Better Patient Care

Best of Oncology Podcast Series

Play Episode Listen Later Jul 23, 2024 21:26


Blood Podcast
Acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL; alternative donor transplantation for severe aplastic anemia; clonal relapse dynamics in AML following allogeneic HCT

Blood Podcast

Play Episode Listen Later Jul 18, 2024 23:32


In this week's episode we'll discuss the safety and efficacy of acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL; learn more about alternative donor transplantation for severe aplastic anemia and discuss clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation.Featured Articles: Acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL: Final efficacy and ctDNA analysis of the CLL2-BAAG trial Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation 

Best of Oncology Podcast Series
EHA HIGHLIGHTS 2024 - LEUKEMIA ROUNDTABLE DISCUSSION: GENETIC INSIGHTS INTO ACQUIRED RESISTANCE AND CLONAL EVOLUTION IN VEN-BASED THERAPY FOR AML

Best of Oncology Podcast Series

Play Episode Listen Later Jun 27, 2024 8:40


VJHemOnc Podcast
CHIP & CCUS: knowledge gaps, ongoing trials & recommendations for approaching patients with myeloid precursors

VJHemOnc Podcast

Play Episode Listen Later Mar 28, 2024 13:02


Clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of unknown significance (CCUS) are considered precursor diseases to hematologic malignancies,... The post CHIP & CCUS: knowledge gaps, ongoing trials & recommendations for approaching patients with myeloid precursors appeared first on VJHemOnc.

Blood Podcast
Identification of rare relapse-initiating stem cells post-transplantation; interferon α impairs erythropoiesis in sickle cell disease; TNFα promotes clonal dominance of KIT D816V+ cells in mastocytosis

Blood Podcast

Play Episode Listen Later Mar 14, 2024 22:48


In this week's episode we'll learn more about rare relapse-initiating stem cells in patients with MDS or AML in complete remission post-transplantation, discuss the role of interferon α in erythropoiesis in sickle cell disease, and learn more about how TNFα promotes clonal dominance of KIT D816V+ cells in mastocytosis.

Aging-US
Exploring Clonal Hematopoiesis and Its Impact on Aging, Cancer, and Patient Care

Aging-US

Play Episode Listen Later Jan 10, 2024 2:58


BUFFALO, NY- January 10, 2024 – A new #editorial paper was #published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 24, entitled, “Exploring clonal hematopoiesis and its impact on aging, cancer, and patient care.” In this new editorial, researchers Julieta Elena Rodriguez, Jean Baptiste Micol and Capucine Baldini from Gustave Roussy discuss clonal hematopoiesis. Clonal hematopoiesis (CH) is a term that refers to the presence in blood cells of hematologic malignancy-associated somatic mutations without fulfilling the diagnostic criteria of hematologic disease. Emerging evidence suggests that CH is a consequence of an expansion of cells harboring initiating driver mutations, potentially linked to the aging hematopoietic system. While these detectable somatic mutations are rare in individuals under 40 years old, they become increasingly prevalent in the elderly population, a term called age-related clonal hematopoiesis (ARCH), reaching up to 18.4% in those aged 90 years or older. Aging itself is a significant stressor associated with CH, particularly in individuals over 70 years old. DNMT3A, TET2, and ASXL1 mutations are more common with advancing age. “Recent evidence also indicates that CH may play a role in solid tumors, such as an increased risk of incident lung cancer [4]. While initial studies associated CH mutations with worse survival outcomes [5], newer findings suggest that solid tumor patients with CH may experience longer survival [6]. However, the underlying mechanisms behind this relationship remain to be elucidated.” DOI - https://doi.org/10.18632/aging.205404 Corresponding author - Capucine Baldini - capucine.baldini@gustaveroussy.fr Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205404 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, clonal hematopoiesis, solid tumors About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

The Genetics Podcast
EP 116: Genetics and Medicine: Clonal hematopoiesis, genomics in healthcare, and a new discovery in APOL1 kidney disease with Dr. Alex Bick

The Genetics Podcast

Play Episode Listen Later Jan 4, 2024 52:34


Join us for our first episode of 2024 as we welcome Dr. Alex Bick, Assistant Professor of Medicine in the Division of Genetic Medicine at Vanderbilt University. In this episode, we will explore the impact of clonal hematopoiesis on cancer and cardiovascular health, examine the integration of genomics in healthcare and preventative medicine, and discuss a recent finding from the Million Veterans Program of a modifier variant in APOL1 kidney disease.

Best of Oncology Podcast Series
ASH HIGHLIGHTS 2023 – LEUKEMIA ROUNDTABLE DISCUSSION: Clonal Hematopoiesis Mutations Detected at the Time of Stopping Tyrosine Kinase Inhibitor Therapy

Best of Oncology Podcast Series

Play Episode Listen Later Dec 15, 2023 3:23


Science (Video)
Clonal Hematopoiesis in Human Aging and Disease with Siddhartha Jaiswal - Sanford Stem Cell Symposium 2023

Science (Video)

Play Episode Listen Later Nov 8, 2023 28:53


Siddhartha Jaiswal, M.D., Ph.D., discusses clonal hematopoiesis and its impact on aging and diseases. Jaiswal highlights the role of genetic variations, focusing on a specific gene, TET2, and its link to clonal expansion. He explains that certain genetic variations can slow clonal expansion, potentially offering insights into treatments or interventions to mitigate its effects. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39260]

Health and Medicine (Video)
Clonal Hematopoiesis in Human Aging and Disease with Siddhartha Jaiswal - Sanford Stem Cell Symposium 2023

Health and Medicine (Video)

Play Episode Listen Later Nov 8, 2023 28:53


Siddhartha Jaiswal, M.D., Ph.D., discusses clonal hematopoiesis and its impact on aging and diseases. Jaiswal highlights the role of genetic variations, focusing on a specific gene, TET2, and its link to clonal expansion. He explains that certain genetic variations can slow clonal expansion, potentially offering insights into treatments or interventions to mitigate its effects. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39260]

University of California Audio Podcasts (Audio)
Clonal Hematopoiesis in Human Aging and Disease with Siddhartha Jaiswal - Sanford Stem Cell Symposium 2023

University of California Audio Podcasts (Audio)

Play Episode Listen Later Nov 8, 2023 28:53


Siddhartha Jaiswal, M.D., Ph.D., discusses clonal hematopoiesis and its impact on aging and diseases. Jaiswal highlights the role of genetic variations, focusing on a specific gene, TET2, and its link to clonal expansion. He explains that certain genetic variations can slow clonal expansion, potentially offering insights into treatments or interventions to mitigate its effects. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39260]

Health and Medicine (Audio)
Clonal Hematopoiesis in Human Aging and Disease with Siddhartha Jaiswal - Sanford Stem Cell Symposium 2023

Health and Medicine (Audio)

Play Episode Listen Later Nov 8, 2023 28:53


Siddhartha Jaiswal, M.D., Ph.D., discusses clonal hematopoiesis and its impact on aging and diseases. Jaiswal highlights the role of genetic variations, focusing on a specific gene, TET2, and its link to clonal expansion. He explains that certain genetic variations can slow clonal expansion, potentially offering insights into treatments or interventions to mitigate its effects. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39260]

Science (Audio)
Clonal Hematopoiesis in Human Aging and Disease with Siddhartha Jaiswal - Sanford Stem Cell Symposium 2023

Science (Audio)

Play Episode Listen Later Nov 8, 2023 28:53


Siddhartha Jaiswal, M.D., Ph.D., discusses clonal hematopoiesis and its impact on aging and diseases. Jaiswal highlights the role of genetic variations, focusing on a specific gene, TET2, and its link to clonal expansion. He explains that certain genetic variations can slow clonal expansion, potentially offering insights into treatments or interventions to mitigate its effects. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39260]

UC San Diego (Audio)
Clonal Hematopoiesis in Human Aging and Disease with Siddhartha Jaiswal - Sanford Stem Cell Symposium 2023

UC San Diego (Audio)

Play Episode Listen Later Nov 8, 2023 28:53


Siddhartha Jaiswal, M.D., Ph.D., discusses clonal hematopoiesis and its impact on aging and diseases. Jaiswal highlights the role of genetic variations, focusing on a specific gene, TET2, and its link to clonal expansion. He explains that certain genetic variations can slow clonal expansion, potentially offering insights into treatments or interventions to mitigate its effects. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39260]

Stem Cell Channel (Audio)
Clonal Hematopoiesis in Human Aging and Disease with Siddhartha Jaiswal - Sanford Stem Cell Symposium 2023

Stem Cell Channel (Audio)

Play Episode Listen Later Nov 8, 2023 28:53


Siddhartha Jaiswal, M.D., Ph.D., discusses clonal hematopoiesis and its impact on aging and diseases. Jaiswal highlights the role of genetic variations, focusing on a specific gene, TET2, and its link to clonal expansion. He explains that certain genetic variations can slow clonal expansion, potentially offering insights into treatments or interventions to mitigate its effects. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39260]

Winning the War on Cancer (Video)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

Winning the War on Cancer (Video)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

Science (Video)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

Science (Video)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

Health and Medicine (Video)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

Health and Medicine (Video)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

University of California Audio Podcasts (Audio)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

University of California Audio Podcasts (Audio)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

Health and Medicine (Audio)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

Health and Medicine (Audio)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

Aging and Senior Health (Audio)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

Aging and Senior Health (Audio)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

Science (Audio)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

Science (Audio)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

UC San Diego (Audio)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

UC San Diego (Audio)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

Winning the War on Cancer (Audio)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

Winning the War on Cancer (Audio)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

Stem Cell Channel (Audio)
Clonal Expansion of Blood Stem Cells in Aging and Leukemia with Leonard Zon - Sanford Stem Cell Symposium 2023

Stem Cell Channel (Audio)

Play Episode Listen Later Nov 1, 2023 48:38


Leonard Zon, M.D., discusses cutting-edge research on the intricate relationship between macrophages, stem cells, and the development of leukemia using the zebrafish model. He delves into the fascinating interactions between these cell types, highlighting the role of a "don't eat me" signal and the influence of the leukemic niche. Through cellular barcoding and single-cell RNA sequencing, he unveils a potential therapeutic target which may offer promising insights into treating leukemia by disrupting the stromal activities that support it. Zon showcases the power of zebrafish models in advancing our understanding of hematopoiesis and cancer, promising new avenues for research and treatment. Series: "Stem Cell Channel" [Health and Medicine] [Science] [Show ID: 39064]

VJHemOnc Podcast
iwAL 2023 Session I: Clonal hematopoiesis in AML, early detection and potential therapeutics

VJHemOnc Podcast

Play Episode Listen Later Sep 15, 2023 18:05


The 5th International Workshop on Acute Leukemias (iwAL 2023) took place in San Diego, CA, and brought together leading experts... The post iwAL 2023 Session I: Clonal hematopoiesis in AML, early detection and potential therapeutics appeared first on VJHemOnc.

Blood Podcast
Poverty and relapse risk in children with ALL, eligibility and enrollment of diverse populations in myeloma trials, and clonal hematopoiesis in VEXAS syndrome

Blood Podcast

Play Episode Listen Later Jul 20, 2023 22:59


In this week's episode, we'll learn more about poverty and relapse risk in children with ALL, discuss eligibility criteria and enrollment of diverse racial and ethnic populations in multiple myeloma clinical trials, and learn more about clonal hematopoiesis in VEXAS syndrome.

PaperPlayer biorxiv neuroscience
Clonal CD8 T cells in the leptomeninges are locally controlled and influence microglia in human neurodegeneration

PaperPlayer biorxiv neuroscience

Play Episode Listen Later Jul 14, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.13.548931v1?rss=1 Authors: Hobson, R., Levy, S. H. S., Flaherty, D., Xiao, H., Ciener, B., Reddy, H., Singal, C., Teich, A. F., Shneider, N. A., Bradshaw, E. M., Elyaman, W. Abstract: Recent murine studies have highlighted a crucial role for the meninges in surveilling the central nervous system (CNS) and influencing CNS inflammation. However, how meningeal immunity is altered in human neurodegeneration and its potential effects on neuroinflammation is understudied. In the present study, we performed single-cell analysis of the transcriptomes and T cell receptor repertoire of 72,576 immune cells from 36 postmortem human brain and leptomeninges tissues from donors with neurodegenerative diseases including amyotrophic lateral sclerosis, Alzheimers disease, and Parkinsons disease. We identified the meninges as an important site of antigen presentation and CD8 T cell activation and clonal expansion and found that T cell activation in the meninges is a requirement for infiltration into the CNS. We further found that natural killer cells have the potential to negatively regulate T cell activation locally in the meninges through direct killing and are one of many regulatory mechanisms that work to control excessive neuroinflammation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

HemeTalks: Conversations in Hematology Education
GENOM: Myelodysplastic Syndromes and Clonal Hematopoiesis

HemeTalks: Conversations in Hematology Education

Play Episode Listen Later Jun 20, 2023 16:31


Dr. Michael Diaz (@mdiazoncmd) and Dr. Namrata Chandhok (@NamrataChandhok) discuss the importance of genomic testing and how to understand and interpret test results when treating patients with myelodysplastic syndromes and clonal hematopoiesis. They also discuss the importance of selecting appropriate therapeutic agents to manage hematologic malignancies. This project is a collaboration between the American Society of Hematology, the Leukemia & Lymphoma Society, and the France Foundation. Access and complete the GENOM modules (for which you can claim CME and MOC credit) via ASH Academy On Demand! Music: "Happy Medium" performed by Zac Nelson, used under license from Shutterstock.

JACC Podcast
Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients with Atherosclerotic Cardiovascular Disease

JACC Podcast

Play Episode Listen Later May 15, 2023 10:09


Commentary by Dr. Valentin Fuster

PaperPlayer biorxiv cell biology
Dual stop codon suppression in mammalian cells with genomically integrated genetic code expansion machinery

PaperPlayer biorxiv cell biology

Play Episode Listen Later Mar 27, 2023


Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.26.534279v1?rss=1 Authors: Meineke, B., Heimgärtner, J., Caridha, R., Block, M., Kimler, K. J., Pires, M. F., Landreh, M., Elsässer, S. J. Abstract: Genetic code expansion via stop codon suppression is a powerful strategy to engineer proteins. Suppressor tRNAs are aminoacylated with noncanonical amino acids (ncAAs) by dedicated aminoacyl-tRNA synthetases (aaRS) and direct ncAA incorporation site-specifically during translation. These pairs of tRNA/aaRS must be orthogonal to the host's tRNAs, aaRS and natural amino acids. Pyrrolysyl-tRNA (PylT)/PylRS pairs from methanogenic archaea, as well as engineered tRNA/aaRS pairs derived from bacteria, are used for genetic code expansion in mammalian cells. Amber suppression is routinely achieved by transient introduction of the components leading to short-term and heterogeneous expression. Here, we demonstrate that stable integration of tRNA/aaRS genes allows for efficient, genetically encoded ncAA incorporation in diverse mammalian cell lines. We extend a general plasmid design and PiggyBac (PB) integration strategy developed for the Methanosarcina mazei PylT/PylRS pair to genomic integration of two tRNA/aaRS pairs of bacterial origin. We further explore suppression of ochre and opal stop codons and parallel incorporation of two distinct ncAAs, both accessible for click chemistry, by dual suppression in stable cell lines. Clonal selection allows for isolation of cells with high dual suppression efficiency and dual site-specific fluorescent labeling of a cell surface receptor using bioorthogonal click chemistries on live mammalian cells. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Blood Podcast
Single-cell genotyping of MDS/CMML clonal output, VTE risk in diffuse glioma, and Del(1p32) is an adverse prognostic factor in myeloma

Blood Podcast

Play Episode Listen Later Mar 16, 2023 20:53


In this week's episode we'll discuss how azacytidine therapy influences the contributions of mutated HSC clones to hematopoiesis in MDS and CMML, learn more about the risk of venous thromboembolism in patients with adult-type diffuse glioma, and discuss the importance of 1p32 deletions as an independent and adverse prognostic factor in myeloma.

Botany One
Clonal Plants Use Smart Connections to Boost Resistance Against Hungry Insects

Botany One

Play Episode Listen Later Mar 15, 2023 5:19


Plants that can reproduce by cloning themselves can share resources and signals to resist herbivores. Clones can change the structure of their leaves according to herbivore stress through the connections between them. You can read the blog post at https://botany.one/2023/03/clonal-plants-use-smart-connections-to-boost-resistance-against-hungry-insects/ You can read the original research at https://academic.oup.com/aobpla/article/15/2/plac062/6894554

Blood Podcast
HSCT for hypomorphic RAG deficiency, EBV-driven lymphoid neoplasms in pediatric ALL, and clonal hematopoiesis and recurrent vascular events in stroke patients

Blood Podcast

Play Episode Listen Later Feb 16, 2023 20:16


In this week's episode we'll discuss the benefits of early diagnosis and hematopoietic stem cell transplant in patients with hypomorphic RAG deficiency, learn more about EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy, and analyze the associations between clonal hematopoiesis and recurrent vascular events and death in patients with ischemic stroke. 

Oncology Data Advisor
Understanding Clonal Hematopoiesis With Rahul Banerjee, Jeremy Meier, and Samuel Rubinstein

Oncology Data Advisor

Play Episode Listen Later Nov 14, 2022 25:45


Dr. Jeremy Meier and Dr. Samuel Rubinstein of the University of North Carolina (UNC) Chapel Hill are the first and senior author, respectively, of a recently published review paper entitled Game of Clones: Diverse Implications for Clonal Hematopoiesis in Lymphoma and Multiple Myeloma. In this interview for Blood Cancer Awareness Month, Oncology Data Advisor's Editorial Board member Dr. Rahul Banerjee speaks with Dr. Meier and Dr. Rubinstein about their work in this area and the future of clonal hematopoiesis research in hematologic malignancies.

JACC Podcast
Impact of Clonal Hematopoiesis in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction

JACC Podcast

Play Episode Listen Later Oct 10, 2022 10:47


Commentary by Dr. Valentin Fuster

VJHemOnc Podcast
Clonal hematopoiesis and pre-MDS states

VJHemOnc Podcast

Play Episode Listen Later Aug 24, 2022 8:52


The relationship between mutations and precursor states in myelodysplastic syndromes (MDS) is a growing area of research, and advances in... The post Clonal hematopoiesis and pre-MDS states appeared first on VJHemOnc.

VJHemOnc Podcast
Clonal hematopoiesis and pre-MDS states

VJHemOnc Podcast

Play Episode Listen Later Aug 24, 2022 8:52


The relationship between mutations and precursor states in myelodysplastic syndromes (MDS) is a growing area of research, and advances in... The post Clonal hematopoiesis and pre-MDS states appeared first on VJHemOnc.

Unfiltered a wine podcast
Ep 105: Viticulture: Rootstocks, Clones, Vineyard design, Trellising, Vine training, Soil prep, Pests and Hazard control (Part 2)

Unfiltered a wine podcast

Play Episode Listen Later Jul 18, 2022 37:39


To download the transcript CLICK HERE PLEASE vote for me at The Peoples Choice Podcast Awards. Voting is open ONLY FOR JULY 2022. I am in the ‘ARTS' Category. CLICK HERE TO VOTE and thank you so much!! This is part 2 of my viticulture series. If you haven't heard part 1, go back to episode 98. However, if you are ready for part two, we are going be looking at rootstocks and clonal selections, then a little bit on vineyard design, how you choose your trellising for the vines. And in fact, training that vine, once you've done that. A small section on preparing your soils and then what you can do during the year, such as green harvesting and leaf stripping. You can choose to plant cover crops, put in an irrigation system, and you will most likely have to deal with pests and funguses, so this is discussed at the end giving a run down of what agrochemical farming is down to organics and then biodynamics.  If you want to skip ahead: 3.50: Rootstocks 8.17: Clonal selection 13.36: Vineyard design 15.33: Trellising choices 19.58: Training of the vine 22.53: Preparing of the soils 25.17: Weeds and cover crops 27.11: Irrigation 29.20: Leaf stripping and green harvesting 30.37: Pests and diseases 32.20: Prevention techniques and organic or biodynamic viticulture Fancy watching some videos on my youtube channel: Eat Sleep Wine Repeat Or come say hi at www.eatsleepwinerepeat.co.uk Or contact me on Instagram @eatsleep_winerepeat or on email: janina@eatsleepwinerepeat.co.uk Until next time, Cheers to you  

Blood Cancer Talks
Episode 1. Implications of Clonal Hematopoiesis

Blood Cancer Talks

Play Episode Listen Later Jul 15, 2022 50:50


In this episode, we bring two experts in clonal hematopoiesis, Dr. Sid Jaiswal from Stanford University and Dr. Alex Bick from Vanderbilt University to dissect the biology, potential clinical implications, and future of clonal hematopoiesis.

Discover CircRes
May 2022 Discover Circ Res

Discover CircRes

Play Episode Listen Later May 19, 2022 30:37


This month on Episode 36 of Discover CircRes, host Cynthia St. Hilaire highlights original research articles featured in the April 29 and May 13 issues of Circulation Research. This episode also features a conversation with Dr Patricia Nguyen and Jessica D'Addabbo from Stanford University about their study, Human Coronary Plaque T-cells are Clonal and Cross-React to Virus and Self.   Article highlights:   Zanoli, et al. COVID-19 and Vascular Aging   Wang, et al. JP2NT Gene Therapy in a Mouse Heart Failure Mode   Harraz, et al. Piezo1 Is a Mechanosensor in CNS Capillaries   Zhao, et al. BAT sEVs in Exercise Cardioprotection   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's journal, Circulation Research. I'm your host, Dr Cyndy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. And today, I'll be highlighting the articles from our April 29th and May 13th issues of Circulation Research. I also will speak with Dr Patricia Nguyen and Jessica D'Addabbo from Stanford University about their study, Human Coronary Plaque T-cells are Clonal and Cross-React to Virus and Self.   Cindy St. Hilaire:        The first article I want to share is titled Vascular Dysfunction of COVID 19 Is Partially Reverted in the Long-Term. The first author is Agostino Gaudio and the corresponding author is Luca Zanoli. And they're from the University of Catania. Cardiovascular complications, such as endothelial dysfunction, arterial stiffness, thrombosis and heart disease are common in COVID 19. But how quickly such issues resolve, once the acute phase of the illness has passed, remains unclear. To find out, this group examined aortic and brachial pulse wave velocity, and other measures of arterial stiffness in 90 people who, several months earlier, had been hospitalized with COVID 19. These measurements were compared with data from 180 controls, matched for age, sex, ethnicity and body mass index, whose arterial stiffness had been assessed prior to the pandemic. 41 of the COVID patients were also examined 27 weeks later to assess any changes in arterial stiffness over time. Together, the data showed arterial stiffness was higher in COVID patients than in controls. And though it improved over time, it tended to remain higher than normal for almost a year after COVID.   Cindy St. Hilaire:        This finding could suggest residual structural damage to the arterial walls or possibly, persistent low-grade inflammation in COVID patients. Either way, since arterial stiffness is a predictor of cardiovascular health, its potential longterm effects in COVID patients deserves further longitudinal studies.   Cindy St. Hilaire:        The second article I want to share is titled Gene Therapy with the N-Terminus of Junctophilin-2 Improves Heart Failure in Mice. The first author is Jinxi Wang and the corresponding author is Long-Sheng Song from the University of Iowa. Junctophilin-2 is a protein with a split personality. Normally, it forms part of the heart's excitation contraction coupling machinery. But when the heart is stressed, JP2 literally splits in two, and sends its N-terminal domain, JP2NT, to the nucleus, where it suppresses transcription of genes involved in fibrosis, hypertrophy, inflammation and other heart failure related processes. However, if this stress is severe or sustained, the protective action of JP2NT is insufficient to halt the progressive failure. This group asked. "What if this N-terminal domain could be ramped up using gene therapy to aid a failing mouse heart?"   Cindy St. Hilaire:        To answer this question, they injected adenoviral vectors encoding JP2NT into mice either before or soon after transaortic constriction, or TAC, tack, which is a method of experimentally inducing heart failure. They found, in both cases, that the injected animals fared better than the controls. Animals injected before TAC showed less severe cardiac remodeling than control mice, while those treated soon after TAC exhibited slower loss of heart function with reduced ventricle dilation and fibrosis. These data suggest that supplementing JP2NT, via gene therapy or other means, could be a promising strategy for treating heart failure. And this data provides a basis for future translational studies.   Cindy St. Hilaire:        The third article I want to share is titled Piezo1 Is a Mechanosensor Channel in Central Nervous System Capillaries. The first and corresponding author is Osama Harraz from the University of Vermont. Neurovascular coupling is the process whereby transient activation of neurons leads to an upsurge in local blood flow to accommodate the increased metabolic needs of the cell. It's known that agents released from active neurons trigger changes in local capillaries that prompt vasodilation, but how these hemodynamic changes are sensed and controlled is not entirely clear. This group suspected that the mechanosensory protein Piezo1, a calcium channel that regulates dilation and constriction of other blood vessels, may be involved. But whether Piezo1 is even found in the microcirculation of the CNS was unknown. This group shows that Piezo1 is present in cortical capillaries of the brain and the retina of the mouse, and that it responds to changes in blood pressure and flow.   Cindy St. Hilaire:        Ex vivo preparations of mouse retina showed that experimentally induced changes in hemodynamics caused calcium transients and related currents within capillary endothelial cells, and that these were dependent on the presence of Piezo1. While it is not entirely clear how Piezo1 influences cerebral blood flow, its pressure induced activation of CNS capillary endothelial cells suggest a critical role in neurovascular coupling.   Cindy St. Hilaire:        The last article I want to share is titled Small Extracellular Vesicles from Brown Adipose Tissue Mediate Exercise Cardioprotection. The first authors are Hang Zhao and Xiyao Chen. And the corresponding authors are Fuyang Zhang and Ling Tao from the Fourth Military Medical University. Regular aerobic exercise is good for the heart and it increases the body's proportion of brown adipose tissue relative to white adipose tissue. This link has led to the idea that brown fat, possibly via its endocrinal activity, might somehow contribute to exercise related cardioprotection. Zhao and colleagues now show that, indeed, brown fat produces extracellular vesicles that are key to preserving heart health. While mice subjected to four weeks of aerobic exercise were better protected against subsequent heart injury than their sedentary counterparts, blocking the production of EVs prior to exercise significantly impaired this protection. Furthermore, injection of brown fat derived EVs into the hearts of mice lessened the impact of subsequent cardiac injury.   Cindy St. Hilaire:        The team went on to identify micro RNAs within the vesicles responsible for this protection, showing that the micro RNAs suppressed an apoptosis pathway in cardiomyocytes. In identifying mechanisms and molecules involved in exercise related cardio protection, the work will inform the development of exercise mimicking treatments for people at risk of heart disease or who are intolerant to exercise.   Cindy St. Hilaire:        Lastly, I want to bring up that the April 29th issue of Circulation Research also contains a short Review Series on pulmonary hypertension, with articles on: The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure, by Olivier Boucherat; Harnessing Big Data to Advance Treatment and Understanding of Pulmonary Hypertension, by Christopher Rhodes and colleagues; New Mutations and Pathogenesis of Pulmonary Hypertension: Progress and Puzzles in Disease Pathogenesis, by Christophe Guignabert and colleagues; Group 3 Pulmonary Hypertension From Bench to Bedside, by Corey Ventetuolo and colleagues; and Novel Approaches to Imaging the Pulmonary Vasculature and Right Heart, by Sudarshan Rajagopal and colleagues; and Understanding the Pathobiology of Pulmonary Hypertension Due to Left Heart Disease, by Jessica Huston and colleagues.   Cindy St. Hilaire:        Today, Dr Patricia Nguyen and Jessica D'Addabbo, from Sanford University, are with me to discuss their study, Human Coronary Plaque T-cells are Clonal and Cross-React to Virus and Self. And this article is in our May 13th issue of Circulation Research. So, Trisha and Jessica, thank you so much for joining me today.   Jessica D'Addabbo:    Thank you for having us.   Patricia Nguyen:         Yes. Thank you for inviting us to your podcast. We're very excited to be here.   Cindy St. Hilaire:        Yeah. And I know there's lots of authors involved in this study, so unfortunately we can't have everyone join us, but I appreciate you all taking the time.   Patricia Nguyen:         This is like a humongous effort by many people in the group, including Roshni Roy Chowdhury, and Xianxi Huang, as well as Charles Chan and Mark Davis. So, we thank you.   Cindy St. Hilaire:        So atherosclerosis, it stems from lipid deposition in the vascular wall. And that lipid deposition causes a whole bunch of things to happen that lead to a chronic inflammatory state. And there's many cells that can be inflammatory. And this study, your study, is really focusing on the role of T-cells in the atherosclerotic plaque. So, before we get into the nitty gritty details of your study, can you share with us, what is it that a T-cell does normally and what is it doing in a plaque? Or rather, let me rephrase that as, what did we know a T-cell was doing in a plaque before your study?   Patricia Nguyen:         So, T-cells, as you know, are members of the adaptive immune system. They are the master regulators of the entire immune system, secreting cytokines and other proteins to attract immune cells to a diseased portion of the body, for example. T-cells have been characterized in plaque previously, mainly with immunohisto chemistry. And their characterization has also been recently performed using single cell technologies. Those studies have been restricted to mainly mirroring studies, studies in mice in their aortic walls, in addition to human carotid arteries. So, it is well known that T cells are found in plaque and a lot of attention has been given to the macrophage subset as the innate immune D. But let's not forget the T-cell because they're actually composed about... 50% in the plaque are T-cells.   Patricia Nguyen:         And we were particularly interested in the T-cell population because we have a strong collaboration with Dr Mark Davis, who's actually the pioneer of T-cell biology and was the first to describe the T-cell receptor alpha beta receptor in his lab in the 1970s. So, he has developed many techniques to interrogate T-cell biology. And our collaboration with him has allowed us and enabled us to perform many of these single cell technologies. In addition, his colleague, Dr Chen, also was pivotal in helping us with the interrogation and understanding of the T-cells in plaque.   Cindy St. Hilaire:        And I think one of the really neat strengths of your study is that you used human coronary artery plaques. So, could you walk us through? What was that like? I collect a lot of human tissue in my lab. I get a lot of aortic valves from the clinic. And it's a lot of logistics. And a lot of times, we're just fixing them, but you are not just fixing them. So, can you walk us through? What was that experimental process from the patient to the Petri dish? And also, could you tell us a little bit about your patient population that you sampled from?   Jessica D'Addabbo:    So, these were coronary arteries that we got from patients receiving a heart transplant. So, they were getting a heart transplant for various reasons, and we would receive their old heart, and someone would help us dissect out the coronary arteries from these. And then, we would process each of these coronary arteries separately. And this happened at whatever hour the hearts came out of the patient.   Jessica D'Addabbo:    So sometime, I was coming in at 3:00 AM with Dr Nguyen and we would be working on these hearts then, because we wanted the samples to be as fresh as possible. So, we would get the arteries. We would digest out the tissue. And then, we would have certain staining profiles that we wanted to look at so that we could put the cells on fax to be able to sort the cells, and then do all the downstream sequencing from there.   Cindy St. Hilaire:        So, in terms of, I don't know, the time when you get that phone call that a heart's coming in to actually getting those single cells that you can either send a fax or send a sequencing, how long did that take, on a good day? Let's talk only about good days.   Jessica D'Addabbo:    Yeah. A lot of factors went into that, sometimes depending on availability of things. But usually, we were ready with all of the materials in advance. So, I'd say it could be anywhere from six to 12 hours, it would take, to get everything sorted. Then, everything after that would happen. But that was just that critical period of making sure we got the cells fresh.   Patricia Nguyen:         So we have to credit the CT surgeons at Stanford for setting up the program or the structure, infrastructure, that enables us to obtain this precious tissue. That is Jack Boyd and Joseph Woo of CT surgery. So, they have enabled human research on hearts by making these tissues available. Because as you know, a transplant... They can say the transplant's happening at 12:00 AM, but it actually doesn't happen until 4:00 AM. And I think it's very difficult for a lab to make that happen all the time. And I think having their support in this paper was critical. And this has allowed us, enabled us, to interrogate kind of the spectrum of disease, especially focusing on T-cells, which are... They make a portion of the plaque, but the plaque itself has not like a million cells that are immune. A lot of them are not immune. So, enabling us to get the tissue in a timely fashion where they're not out of the body for more than 30 minutes enables us to interrogate these small populations of cells.   Cindy St. Hilaire:        That's actually the perfect segue to my next question, which is, how many cells in a plaque were you able to investigate with the single cell analysis? And what was the percentage again of the T-cells in those plaques or in... I guess you looked at different phases of plaque. So, what was that spectrum for the percentage of T-cells?   Patricia Nguyen:         So, for 10X, for example, you need a minimum of 10,000 captured cells. You could do less, but the utility of the 10X is maximized with 10,000. So, many times before the ability to multiplex these tissues, we were doing like capturing 5,000 for example. And the number of cells follows kind of the disease progression, in the sense that as a disease is more severe, you have more immune cells, in general. And it kind of decreases as it becomes more fibrotic and scarred, like calcified. So, it was a bit challenging to get very early just lipid-only cells. And a lot of those, we captured like 3000 or something like that. And efficiency is like 80% perhaps. So, you kind of capture…   Cindy St. Hilaire:        And also, how many excised hearts are going to have early athero? So, it's...   Patricia Nguyen:         Well, there are... nonischemics will have...   Cindy St. Hilaire:        Oh, okay. Okay.   Patricia Nguyen:         So, the range was nonischemic to ischemic.   Cindy St. Hilaire:        Oh great.   Patricia Nguyen:         So, about a portion... I would say one third of the total heart transplants were ischemic. And a lot of them were non ischemic. But as you know, the nonischemic can mix with ischemia. And so, they could have mild to moderate disease in the other arteries, for example, but not severe like 70%/90% obstruction.   Cindy St. Hilaire:        Wow. That's so great. That's amazing. Amazing sample size you have. So T-cell, it's kind of an umbrella term, right? There's many different types of T-cells. And when you start to get in the nitty gritty, they really do have distinct functions. So, what types of T-cells did you see and did you focus on in this study?   Jessica D'Addabbo:    So, the two main types of T-cells are CD4 positive T-cells and CD8 positive T-cells. And we looked at both of these T-cells from patients. We usually sorted multiple plates from each. And then, with 10X, we captured both. But our major finding was actually that the CD8 positive t-cell population was more clonally expanded than the CD4 population, which led us to believe that these cells were more important in the coronary artery disease progression and in the study that we were doing because for a cell to be clonally expanded, it means it was previously exposed to an antigen. And so, if we're finding these T-cells that are clonally expanded in our plaques, then we're hypothesizing that they were likely exposed to some sort of antigen, and then expanded, and then settled into the plaque.   Cindy St. Hilaire:        And when you're saying expansion, are you talking about them being exposed to the antigen in the plaque and expanding there? Or do you think they're being triggered in the periphery and then honing in as a more clonal population?   Patricia Nguyen:         So, that's a great question. And unfortunately, I don't have the answer to that. So basically-   Jessica D'Addabbo:    Next paper, next paper.   Patricia Nguyen:         Exactly. So, we... Interesting to expand on Jessica's answer. Predominantly what was found, as you said, was memory T-cells, so memory T-cells expressing specific markers, so memory versus naive. And these were effector T-cells. And memory meaning they were previously expanded by antigen engagement, and just happened to be in the plaque for whatever reason. We do not know why T-cells specifically are attracted to the plaque, but they are obviously there. And they're in a memory state, if you will. And some of them did display activation markers, which suggested that they clonally expanded to an antigen. What that antigen is, is the topic of another paper. But certainly, it is important to understand that these patients that we recruit, because they were transplant patients, they're not actively infected, right? That is a exclusionary criteria for transplants, right?   Patricia Nguyen:         So, that means these T-cells were there for unclear reasons. Why they're there is unclear. Whether they are your resident T-cells also is unclear, because the definition of resident T-cell still remains controversial. And you actually have to do lineage tracking studies to find out, "Okay, where... Did they come from the bone marrow? Did they come from the periphery? How did they get there?" Versus, "Okay. They were already there and they just expanded, for whatever reason, inside the plaque."   Cindy St. Hilaire:        So, your title... It was a great title, with this provocative statement, "T-cells are clonal and cross react to virus and self." So, tell us a little bit more about this react to virus and self bit. What did your data show?   Jessica D'Addabbo:    So, because of the way we sequenced the T-cell receptor, we were able to have paired alpha and beta chains. And because we knew the HLA type of the patients, we were able to put the sequences that we got out after we sequenced these through an algorithm called GLIPH, which allows us to look at the CDR3 region of the T cell receptor, which is the epitope binding region. And there are certain peptide. They're about anywhere from three to four amino acids long. These are mapped to certain binding specificities to known peptides. And so, basically, we were able to look at which epitopes were most common in our plaques. And we found that after comparing these to other epitopes, that these were actually more binding to virus. Patricia Nguyen:         So let me add to what Jessica stated, and kind of emphasize the value of the data set, if you will. So, this is, I believe, the first study that provides the complete TCR repertoire of coronary plaque, and actually any plaque that I know of, which is special because we know that there is specificity of TCR binding. It's more complicated than the antibody that binds directly from B cells to the antigen, because the T-cells bind processed antigen. So, the antigens are processed by antigen presenting cells like Dendritic cells and macrophages. And they have a specific HLA MHC class that they need to present to. And they need both arms, the antigen epitope and the MHC, to activate the T-cell. So unfortunately, it's not very direct to find the antigen that is actually activating the T-cell because we're only given a piece of it. Right?            Patricia Nguyen:         But we have provided a comprehensive map of all the TCRs that we find in the plaque. And these TCRs have a sequence, an immuno acid sequence. And luckily, in the literature, there is a database of all TCR specificities. Okay. So, armed with our TCR repertoire, we can then match our TCR repertoire with an existing database of known TCR specificities. Surprisingly, the matching TCRs are specific to virus, like flu, EBV and CMB. And also, because this was done in the era of COVID, we thought it would be important to look at the coronavirus database. We did find that there were matches to the coronavirus database. Even though our finding is not specific to SARS, it does lend to some potential mechanistic link there as well.   So, because this is all computational, it is important to validate. So, the importance of validation requires us to put the TCR alpha beta chain into a Jurkat cell, which is a T-cell line that does not have alpha beta chains on it, and then expose it to what we think is the cognate antigen epitote, with the corresponding HLA MHC APC. Because you don't have all those pieces, it will not work. Yes. So importantly, we did find that what we predicted to have the specificity of a flu peptide had specificity to a flu peptide.   Patricia Nguyen:         So then, the important question was, "Okay, these patients aren't infected, right? Why are these things here? Is there a potential cross reactivity with self peptides?"   Patricia Nguyen:         So luckily, our collaborator, Dr Charles Chan, was able to connect us with another computational algorithm that he was familiar with, whereby we were able to take the peptide sequences from the flu and match them with peptide sequencing from proteins that are self and ubiquitous. And we demonstrated, again, these T-cells were activated in vitro. That is why we concluded that there's a potential cross reactivity between self and virus that can potentially lead to thrombosis associated with viral infections. Of course, this all needs to be proved in vivo.   Cindy St. Hilaire:        Sure, sure.   Patricia Nguyen:         It's that first step for other things.   Cindy St. Hilaire:        The other big immune cell that we know is in atherosclerotic plaques and that's macrophages. And they can help to present antigens and things like that. And they also help to chew up the necrotic bits. And so, do you think that this T-cell component is an earlier, maybe disease driving, process or an adaptive process that goes awry as a secondary event? Patricia Nguyen:         So, I'm a fan of the T-cell. So... I'm with team T cell. I would like to think that it is playing an active role in pathology in this case and not a reactive role, in the sense of just being there. I think that the T-cell is actively communicating with other cells within the plaque, and promoting pro fibrotic and pro inflammatory reactions, depending on the T-cell. So, a subset of this paper was looking at kind of the interactions between the T-cell and other cells within the plaque, like macrophages and smooth muscle cells. And as we know, T-cells are activated and they produce cytokines. Those cytokines then communicate to other cells. And we found that, computationally, when you look at the transcriptome, there is a pro-inflammatory signature of the T-cell that resides in the more complex stage. And then, there's an anti-inflammatory signature that kind of resides in the transition between lipid and fibro atheroma, if you will.   Cindy St. Hilaire:        So, do you know, or is it known, how dynamic these populations are? Obviously, the hearts that you got, the samples you got, didn't have active infections. But do you know perhaps even how long ago they happened, or even how soon after there might be an infection or an antigen presented that you could get this expansion? And could that be a real driver of rupture or thrombosis?   Patricia Nguyen:         So, in theory, you would suppose that T-cells expanding and dividing and producing more and more cytokines would then lead to more macrophages coming, more of their production of proteinases that destroy the plaque. Right? So yes, in theory, yes. I think it's very difficult to kind of map the progression of T cell clonality in the current model that we have, because we're just collecting tissues. However, in the future, as organoids become more in science and kind of a primary tissue, where we can... For example, Mark Davis is making organoids with spleen, and also introducing skin to that.   Patricia Nguyen:         And certainly, we could think of an organoid involving the vasculature with immune cells introduced. And so, I think, in the next phase, project 2.0, we can investigate what... like over time, if you could model atherosclerosis and the immune system contribution, T-cells as well as macrophages and other immune cells, you can then kind of map how it happens in humans. Because obviously, mice are different. We know that mice... Actually, the models of transgenic mice do not rupture. It's very hard to make them rupture. Right?   Cindy St. Hilaire:        Well, if you stop feeding them high fat diet, the plaque goes away.   Patricia Nguyen:         For sure, for sure. So I think.. I mean, Mark Davis is a huge proponent of human based research, like research on human tissue. And as a physician scientist, obviously I'm more inclined to do human based research. And Jessica's going to be a physician someday soon. And I'm sure she's more inclined to do human based research. And certainly, the mouse model and in vitro models are great because you can manipulate them. But ultimately, we are trying to cure human diseases.   Cindy St. Hilaire:        Mice are not little humans. That's what we say in my lab. I similarly do a lot of human based stuff and it's amazing how great mice are for certain things, but still how much is not there when we need to really fully recapitulate a disease model.   So, my last question is kind of regarding this autoimmune angle of your findings. And that is, women tend to have more autoimmune diseases than men, but due to the fact that you are getting heart transplants, you've got a whole lot more men in your study than women. I think it was like 31 men to four women. But, I mean, what can you do? It's the nature of heart transplants. But I'm wondering, did you happen to notice...Maybe the sample size perhaps is too small, but were there any differences in the populations of these cells between women and men? And do you think there could be any differences regarding this more prevalence of autoimmune like reactions in women?   Patricia Nguyen:         So, that's an interesting question, but you hit it on the nose when you said "Your sample is defined mainly by men." And in addition, the samples that were women tend to have less disease. And they tend to be nonischemic in etiology. So, I think that kind of restricts our analysis. And perhaps, I guess, future studies could model using female tissues, for example, instead of only male. But the limitation of all human studies is sample availability. And perhaps, human organoid research can be less limited by that. And certainly, mouse research has become more evenly distributed of male and female mice.   Cindy St. Hilaire:        Yeah. Suffice it to say, human research is hard, but you managed to do an amazing and really important study. It was really elegant and well done. Congratulations on what is an epic amount of time. 12-hour experiments are no joke, and really beautiful data. So, thank you so much for joining me today, Dr Nguyen and Miss almost Dr D'Addabbo. Congrats and I'm really looking forward to seeing your future work.   Jessica D'Addabbo:    Thank you so much.   Patricia Nguyen:         Thanks so much.   Jessica D'Addabbo:    Thank you for having us. This is wonderful.   Cindy St. Hilaire:        That's it for the highlights from the April 29th and May 13th issues of Circulation Research. Thank you so much for listening. Please check out the Circ Res Facebook page and follow us on Twitter and Instagram with the handle @Circres and #Discover CircRes. Thank you to our guests: Dr Patricia Nguyen, and soon to be Doctor, Jessica D'Addabbo, from Stanford University.   This podcast was produced by Ishara Ratnayaka, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Copy text for the highlighted articles was provided by Ruth Williams. I'm your host, Dr Cindy St. Haler. And this is Discover CircRes, you're on the go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2022. The opinions expressed by the speakers of this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, visit aha journals.org.  

Star Wars at the Movies
Ep 20: Clonal Recall

Star Wars at the Movies

Play Episode Listen Later May 16, 2022 121:06


The 20th installment of the podcast commemorates 20 years of Attack of the Clones with a battalion of fans and friends sharing their Episode II recollections and reflections. From online spoiler forums and Celebration II to red carpet encounters and the hunt for the elusive “digi-proj,” 2002 springs back to life like an incredibly old frog dueling an evil retired Jedi in this retrospective on a movie created at a pivotal crossroads of cinematic art and technology.

The Black Wine Guy Experience
Go Your Own Way: Diane Carpenter on Somms, Streaming, and Clonal Selection

The Black Wine Guy Experience

Play Episode Listen Later Mar 21, 2022 86:40


MJ's guest today is owner of Ross Knoll Vineyard, Co-founder and Board Member for SommTV, and executive producer for SOMM Films, Diane Carpenter. In 2017 Diane and her husband David of 34 years cultivated their own vineyard in Sonoma County, California and planted 3000 Calera Clone Pinot Noir vines. Two years later, Diane and her colleagues created SommTV, where Diane has been an Executive Producer on Somm: Into the Bottle and SOMM 3. Diane is also Co-Founder and Board Member of Forgotten Man Films, where they produce the ongoing SOMM series. In this episode, MJ and Diane discuss her upbringing in England, meeting her husband, and moving to America. Diane details her journey through wine, from the glass that sparked her passion to getting her hands dirty in wine country for the first time to starting SommTV. She shares how she has balanced raising a family and pursuing a career.A huge thank you to Diane Carpenter! Check out her website and join her mailing list: www.dianecarpenter.orgFollow her on IG at @yourwinestylistThis episode's in studio wine:2020 Ross Knoll Rose Cuvee Chelsea ___________________________________________________________For insider info from MJ and exclusive content from the show sign up at Blackwineguy.comFollow MJ @blackwineguy Thank you to our sponsor: Taub Family Selections. Taub Family Selections is a dynamic fourth generation, family-owned wine import company with a truly enviable portfolio of fine wines from 11 countries. They are proud to represent an exceptional portfolio of high quality, terroir centric and historic producers from around the world, including Italy and France - where they have an exciting roster of burgeoning vignerons from Burgundy coming your way soon. Learn more at www.taubfamilyselections.comThank you to our sponsor: Independence Wine and Spirits - or IWS. IWS is one of the hot up and coming distributors of fine wines and spirits headquartered in New York City. Like Taub Family Selections, IWS is owned by the Taub family, who have re-entered the NY wholesale market, bringing the family back to its roots in distribution where they held court from 1951 – 2004. To learn more about IWS go to: https://independencewine.com Thank you to our sponsor: Ross Knoll Vineyard Wines is a female owned company which produces handcrafted wines with winemaker, Justin Seidenfeld, made from Pinot Noir grapes sourced from exceptional vineyards in the Russian River Valley. Go to rossknollvineyard.com and join their waitlist for the 2021 vintage Pinot Noir which will be released early 2022.Thank you to our sponsor: SOMM TV. SOMM TV is a streaming network focused on the world of wine, food, and travel. Many call it the "Netflix" of wine & food!Use code MJ60 at checkout and get your first year of SOMM TV at 60% off! That's only $20 for the whole year!Checkout Link: http://watch.sommtv.com/checkout?code=mj60&plan=yearly See acast.com/privacy for privacy and opt-out information.

JACC Speciality Journals
JACC: CardioOncology - Cardiovascular Disease Among Patients with Acute Myeloid Leukemia and Clonal Hematopoiesis of Indeterminate Potential(CHIP)-Related Mutations

JACC Speciality Journals

Play Episode Listen Later Mar 15, 2022 3:16


Outliving Cancer
Cancer as a Clonal Disease

Outliving Cancer

Play Episode Listen Later Mar 1, 2022 26:37


Dr. Nagourney today discusses how cancer is a clonal disease, and how that impacts potential treatm

Trainee Pearls
#4 Christopher Gibson: Clonal Hematopoiesis and transplantation

Trainee Pearls

Play Episode Listen Later Jan 21, 2022 40:01


Clonal hematopoiesis (CH) is an age-related, asymptomatic condition in which leukemia-associated somatic mutations are detected in the blood of individuals without a hematologic malignancy. In the nontransplant setting, CH is uniformly associated with adverse outcomes, including an elevated risk of developing hematologic malignancies and an increased risk of nonhematologic outcomes because of altered inflammatory signaling. Current evidence has thus been insufficient to resolve disagreement about whether to screen older candidate donors for CH, and some transplant centers have begun excluding donors found to have CH on the basis of the assumption that the adverse associations of native CH also apply in the context of transplant. This study performed a comprehensive analysis of samples from donors age 40 years or older to determine the impact of CH on overall recipient outcomes, risk of DCL, and measures of graft alloimmune activity. Article: https://ascopubs.org/doi/full/10.1200/JCO.21.02286

Wetenschap Vandaag | BNR
Wat te doen met een leger gekloonde marmerkreeften?

Wetenschap Vandaag | BNR

Play Episode Listen Later Jan 19, 2022 6:08


Ze wordt gezien als één van de hardnekkigste invasieve diersoorten: de marmerkreeft. Nu proberen onderzoekers te ontdekken of het diertje - dat zichzelf razendsnel voortplant - ons ook kan helpen.  Een behoorlijke plaag is het dier dat zich over de hele wereld heeft verspreid inmiddels. Terwijl het ooit begon met één oermoeder. Een afstammeling van de Noord-Amerikaanse rivierkreeft. Die moeder kwam in 1995 via een dierenmarkt in Duitsland in een aquarium terecht en daar begon ze aan haar leger van kinderen. Ze heeft inmiddels miljoenen nakomelingen die allemaal genetisch identiek zijn. Daar kwamen Duitse wetenschappers tot hun verbazing achter toen ze in 2018 het genoom van de moeder en andere marmerkreeften - die overal over de wereld werden teruggevonden - bestudeerden. Bijna geen genetische verschillen. Er komen bij de voortplanting van dit dier geen mannen kijken, dat kan ze zelf. Parthenogenese heet het. Eigenlijk is het gewoon klonen. Als je daarover nadenkt is het nogal apart dat veel diersoorten juist zoveel mogelijk genetische variatie nastreven om een gezonde populatie te krijgen, maar deze kreeft het zo bizar goed doet met nauwelijks genetische variatie.  Omdat dat klonen overeenkomsten heeft met hoe een tumor in een lichaam groeit is het dier sinds het onderzoek in 2018 ook een model voor kankeronderzoek. Maar wat moeten we er verder mee? Daar zijn wel wat ideeën voor.  Met dank aan dit uitgebreide artikel in The Guardian: ‘We started eating them': what do you do with an invasive army of crayfish clones? De paper uit 2018 vind je hier: Clonal genome evolution and rapid invasive spread of the marbled crayfish.  See omnystudio.com/listener for privacy information.

Room For Improvement
42: Tedious Pedantry

Room For Improvement

Play Episode Listen Later Mar 4, 2018 49:53


Wikipedias discussed in today's episode: www.wikipedia.org/wiki/Lithuania_Governorate www.wikipedia.org/wiki/The_Shrine_(film) www.wikipedia.org/wiki/%C5%A0koda_Rapid_(1935%E2%80%9347) www.starwars.wikia.com/wiki/Gonky www.wikipedia.org/wiki/Family_reunion www.wikipedia.org/wiki/Galbi-jjim www.wikipedia.org/wiki/Ruhaga_of_Toro www.wikipedia.org/wiki/Clonal_colony