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A Tale of Sensitive Information
 
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Description: Confidential. Classified. Critical. Sensitive. Heard these words floating around before? Chances are you may work with sensitive information, or maybe you’re wondering, “What is sensitive information?”. From protected health information (PHI), to personally identifiable information (PII), to financial information, to research and administrative data, watch this video to learn more about the different types of sensitive information. When you work with sensitive information, it is your responsibility to protect it. Author: NIH
Views: 7769 nihvcast
Stress and Health: From Molecules to Societies
 
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Air date: Wednesday, October 28, 2009, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Few Westernized humans are likely to die of scarlet fever, malaria or malnutrition. Instead, we live well enough and long enough to succumb to the diseases of slow degeneration. It is increasingly recognized that a large percentage of such diseases can be caused by or worsened by stress. This lecture approaches the subject of stress and health from two very different perspectives. To learn more about Dr. Sapolsky, visit http://wals.od.nih.gov/2009-2010/october2009x.html The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Runtime: 01:10:29 NLM Title: Stress and health : from molecules to societies [electronic resource] / Robert Sapolsky. Series: NIH director's Wednesday afternoon lecture series Author: Sapolsky, Robert M. National Institutes of Health (U.S.) Publisher: [Bethesda, Md. : National Institutes of Health, 2009] Other Title(s): NIH director's Wednesday afternoon lecture series Abstract: (CIT): Few Westernized humans are likely to die of scarlet fever, malaria or malnutrition. Instead, we live well enough and long enough to succumb to the diseases of slow degeneration. It is increasingly recognized that a large percentage of such diseases can be caused by or worsened by stress. This lecture approaches the subject of stress and health from two very different perspectives. To learn more about Dr. Sapolsky, visit http://wals.od.nih.gov/2009-2010/october2009x.html The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Subjects: Glucocorticoids--adverse effects Hippocampus--physiopathology Stress, Physiological--physiology Stress, Psychological--physiopathology Publication Types: Government Publications Lectures Webcasts Permanent link: http://videocast.nih.gov/launch.asp?15399
Views: 102176 nihvcast
Protecting Yourself From Identity Theft Online
 
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Protecting Yourself From Identity Theft Online NIH Office of the CIO
Views: 7536 nihvcast
Trusted Insider
 
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IT Training
Views: 11790 nihvcast
In Search of the Holy Grail of Fly Motion Vision
 
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Air date: Wednesday, March 16, 2011, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Neurons responding to moving stimuli in a directionally selective way are found in the visual systems of almost all species, yet the underlying neural mechanisms and circuits giving rise to this particular response property are still elusive. In the fly, large motion-sensitive neurons located in the so-called ' lobula plate' respond to optic flow stimuli. These cells receive input from a retinotopically organized array of local motion-sensitive elements which are described in quantitative detail by a formal model called the 'Reichardt detector'. However, despite decades of research, it is still not known what neurons constitute the Reichardt detector and what biophysical mechanisms underlie the mathematical operations postulated in this model. Thus, the neural implementation of the Reichardt detector somehow became the 'holy grail' of fly motion vision. The talk will summarize some recent progress made along this direction, using the fruit fly Drosophila melanogaster and combining electrophysiology with the powerful genetics available in this organism. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Author: Dr. Alexander Borst, Max Planck Institute of Neurobiology Runtime: 00:59:55 Permanent link: http://videocast.nih.gov/launch.asp?16532
Views: 1677 nihvcast
Regulation of growth by the mTOR pathway
 
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Regulation of growth by the mTOR pathway Air date: Wednesday, March 20, 2013, 3:00:00 PM Wednesday Afternoon Lecture Series The mammalian target of rapamycin (mTOR), the target of the immunosuppressive drug rapamycin, is the central component of a nutrient- and hormone-sensitive signaling pathway that regulates cell growth and proliferation. This pathway becomes deregulated in many human cancers and plays an important role in the control of metabolism and aging. Sabatini's lab has identified two distinct mTOR-containing proteins complexes, one of which regulates growth through S6K and another that regulates cell survival through Akt. These complexes, mTORC1 and mTORC2, define both rapamycin-sensitive and insensitive branches of the mTOR pathway. New results on the regulation and functions of the mTORC1 and mTORC2 pathways will be discussed. Author: David M. Sabatini, M.D., Ph.D., MIT Runtime: 00:59:04 Permanent link: http://videocast.nih.gov/launch.asp?17962
Views: 44843 nihvcast
Is Aging Reversible? Resetting the Clock
 
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Is Aging Reversible? Resetting the Clock Air date: Wednesday, September 12, 2012, 3:00:00 PM Description: Wednesday Afternoon Lecture Series The Annual Florence Mahoney Lecture Aging is a process that is generally viewed as unidirectional, relentless, and inevitable. However, in addition to the existence of non-aging species, or at least species with negligible senescence, data from a wide range of living organisms suggests that environmental influences can markedly slow and even halt the aging process. Furthermore, recent experimental evidence suggests that aspects of the molecular and functional characteristics of aged cells and tissues even in mammals can be restored to a more youthful state. Analyses of age-related changes in cells have revealed clear epigenetic changes, and the reversibility of some of those processes, in essence leading to cell and tissue rejuvenation, suggest epigenetic mechanisms. Current studies focus on understanding the nature and regulation of those epigenetic mechanisms and the extent to which the aging clock can be rewound or reset by defined environmental influences while leaving other cellular characteristics, such as their state of differentiation, intact. For more information go to http://wals.od.nih.gov Author: Thomas A. Rando, M.D., Ph.D., Stanford University School of Medicine Runtime: 01:02:40 Permanent link: http://videocast.nih.gov/launch.asp?17556
Views: 13502 nihvcast
Induction of Pluripotency by Defined Factors
 
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Air date: Thursday, January 14, 2010, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Human ES cells have been expected as suitable resources for cell transplantation therapies. However, it has sparked ethical controversy and causes immune rejection. Hence, we decided to generate an ideal pluripotent stem cell for innovative medicine. At first, we constructed a pluripotency assay system that the candidate factors are introduced into neonate fibroblasts via retrovirus vectors. As the result, the set of Oct3/4, Sox2, c-Myc, and Klf-4 gave rise to drug resistant colonies implying potential pluripotency. The survived cells resembled ES cells in terms of morphology and proliferation showed ES cell markers and formed teratoma. It was named as induced pluripotent stem cell (iPS cell). iPS cells were created even from adult mouse fibroblasts. Moreover, iPS cells based on Nanog-expression demonstrated germline transmission. Furthermore, we successfully generated iPS cells from human adult fibroblasts, using a modified protocol. However, tumor formation was observed in chimera mouse, probably due to c-Myc retrovirus integrated into genome. We re-modified the protocol and successfully established iPS cells without using c-Myc. As further effort to lower a risk of tumorigenesis, we recently succeeded in developing a virus-free method - using a pair of plasmid vectors, instead of retrovirus vectors, to introduce the four genes into mouse fibroblasts. Further research results are discussed from the points of safety and induction efficiency of iPS cells for future clinical grade. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Runtime: 01:09:50 NLM Title: Induction of pluripotency by defined factors [electronic resource] / Shinya Yamanaka. Series: NIH director's Wednesday afternoon lecture series Author: Yamanaka, Shinya. National Institutes of Health (U.S.) Publisher: [Bethesda, Md. : National Institutes of Health, 2010] Other Title(s): NIH director's Wednesday afternoon lecture series Abstract: (CIT): Human ES cells have been expected as suitable resources for cell transplantation therapies. However, it has sparked ethical controversy and causes immune rejection. Hence, we decided to generate an ideal pluripotent stem cell for innovative medicine. At first, we constructed a pluripotency assay system that the candidate factors are introduced into neonate fibroblasts via retrovirus vectors. As the result, the set of Oct3/4, Sox2, c-Myc, and Klf-4 gave rise to drug resistant colonies implying potential pluripotency. The survived cells resembled ES cells in terms of morphology and proliferation showed ES cell markers and formed teratoma. It was named as induced pluripotent stem cell (iPS cell). iPS cells were created even from adult mouse fibroblasts. Moreover, iPS cells based on Nanog-expression demonstrated germline transmission. Furthermore, we successfully generated iPS cells from human adult fibroblasts, using a modified protocol. However, tumor formation was observed in chimera mouse, probably due to c-Myc retrovirus integrated into genome. We re-modified the protocol and successfully established iPS cells without using c-Myc. As further effort to lower a risk of tumorigenesis, we recently succeeded in developing a virus-free method - using a pair of plasmid vectors, instead of retrovirus vectors, to introduce the four genes into mouse fibroblasts. Further research results are discussed from the points of safety and induction efficiency of iPS cells for future clinical grade. Subjects: Induced Pluripotent Stem Cells--physiology Induced Pluripotent Stem Cells--transplantation Publication Types: Government Publications Lectures Webcasts Permanent link: http://videocast.nih.gov/launch.asp?15547 wals011410
Views: 43175 nihvcast
Wizardry of Tissue Repair and Regeneration: A Tale of Skin Cells when their Magic is all but Gone
 
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Air date: Wednesday, March 07, 2012, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Views: Total views: 95, (4 Live, 91 On-demand) Category: Wednesday Afternoon Lectures Description: Current research focus of Dr. Tomic-Canic is molecular and cellular mechanisms of wound healing and its inhibition with the long-term goal to bring bench-side research back to patients at the bedside. Her research includes human and diabetic models of wound healing, wound genomics analyses, generating primary cells from patients' wound biopsies, local sustained gene delivery, cellular assays of wound healing, and histology and immunohistochemistry of skin. Dr. Tomic-Canic and her colleagues, supported in part by NINR, made several fundamental discoveries in the field of wound healing research. These discoveries include identification of the one of the first genes and unique molecular pathway that stops wounds from healing; a novel molecular mechanism though which corticosteroids inhibit wound healing; biomarkers that can guide the extent surgical debridement; establishment of human wound tissue/cell bank; new drugs that accelerate healing. Dr Tomic-Canic has an established track record of successfully bringing basic science discovery to clinical use for wound patients. Her lab has identified molecular markers that may predict clinical outcome of non-healing and guide surgical debridement of chronic ulcers, which are currently being validated in an NIH-sponsored clinical trial. The NIH Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. For more information, visit: The NIH Director's Wednesday Afternoon Lecture Series Author: Marjana Tomic-Canic, Ph.D., R.N., University of Miami Miller School of Medicine Runtime: 01:06:48 Permanent link: http://videocast.nih.gov/launch.asp?17147
Views: 6047 nihvcast
IPPCR 2016: Concepts in Pharmaceutical Development Project Management
 
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IPPCR 2016: Concepts in Pharmaceutical Development Project Management Air date: Monday, February 01, 2016, 5:00:00 PM Category: IPPCR Runtime: 00:48:04 Description: The Introduction to the Principles and Practice of Clinical Research (IPPCR) is a course to train participants on how to effectively conduct clinical research. The course focuses on the spectrum of clinical research and the research process by highlighting epidemiologic methods, study design, protocol preparation, patient monitoring, quality assurance, and Food and Drug Administration (FDA) issues. For more information go to http://clinicalcenter.nih.gov/training/training/ippcr1.html Author: Christopher D. Breder, M.D., Ph.D., FDA Permanent link: http://videocast.nih.gov/launch.asp?19461
Views: 4933 nihvcast
What We Have Learned from Structures of the Ribosome
 
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Air date: Wednesday, April 27, 2011, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: The publication of the atomic structures of the 50S and 30S ribosomal subunits in 2000 revolutionized our understanding of protein synthesis. In my talk I will focus on our work, initially on the 30S subunit and subsequently on the entire 70S ribosome, focusing on how the ribosome facilitates the accurate translation of the genetic code. The NIH Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. For more information, visit: The NIH Director's Wednesday Afternoon Lecture Series Author: Venki Ramakrishnan, Ph.D., Nobel Laureate and MRC Laboratory of Molecular Biology in Cambridge, UK Runtime: 01:02:23 Permanent link: http://videocast.nih.gov/launch.asp?16615
Views: 6536 nihvcast
A Mitochondrial Etiology of Metabolic and Degenerative Diseases, Cancer and Aging
 
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A Mitochondrial Etiology of Metabolic and Degenerative Diseases, Cancer and Aging Air date: Wednesday, April 02, 2014, 3:00:00 PM Category: Wednesday Afternoon Lectures Runtime: 01:10:05 Description: Wednesday Afternoon Lecture Series For half a millennium Western medicine has focused on anatomy and for the past century on nuclear DNA (nDNA), Mendelian, genetics. While these concepts have permitted many biomedical advances, they have proven insufficient for understanding the common "complex" diseases. Life requires energy, 90 percent of which comes from the mitochondrion. The mitochondrial genome consists of thousands of copies of the maternally inherited mitochondrial DNA (mtDNA) plus 1,000--2,000 nDNA genes. The mtDNA has a very high mutation rate, but the most deleterious mutations are removed by an ovarian prefertilization selection system. Hence, functional mtDNA variants are constantly being introduced into the human population, the more deleterious resulting in recent maternally inherited diseases. The milder mtDNA variants have accumulated sequentially as women spread throughout Africa and migrated out to colonize Eurasia and the Americas. Some ancient mtDNA variants alter mitochondrial energy metabolism in ways that were beneficial in different regional environments. In alternative environments and/or with age these same adaptive variants can be maladaptive and increase the risk for disease. For example, one variant increases the penetrance of mutations associated with an inherited form of vision loss, but is adaptive for survival at high altitudes. Mutations in the mtDNAs also accumulate with age in both stem and somatic tissue cells and can be associated with various forms of cancer. The introduction of mtDNA variants into the mouse germline via female embryonic stem cells has confirmed the causal role of mitochondrial deficiency in diseases. Hence, the pathophysiology of some common diseases may be bioenergetic dysfunction and their genetic complexity the result of thousands of nDNA and mtDNA bioenergetic gene variants interacting. For more information go to http://wals.od.nih.gov Author: Douglas Wallace, Perelman School of Medicine at the University of Pennsylvania Permanent link: http://videocast.nih.gov/launch.asp?18367
Views: 29652 nihvcast
Engineering T cells: moving beyond leukemia
 
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Engineering T cells: moving beyond leukemia Air date: Wednesday, September 28, 2016, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 00:49:33 Description: NIH Director’s Wednesday Afternoon Lecture Series It is now well established that the immune system can control and eliminate cancer cells. Adoptive T-cell transfer has the potential to overcome the significant limitations associated with vaccine-based strategies in patients who are often immune compromised. Dr. June will discuss how the emerging discipline of synthetic biology-which combines elements of genetic engineering and molecular biology to create new biological structures with enhanced functionalities-can be applied to cancer. He will also talk about the outlook for chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies, including managing toxicities and expanding the availability of personalized cell therapy as a promising approach to all hematologic malignancies and solid tumors. Many questions remain in the field of CAR T cells, but the encouraging response rates pave a wide road for future investigation. Carl June is the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine. He is currently Director of the Center for Cellular Immunotherapies at the Perelman School of Medicine, and Director of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania. He is a graduate of the Naval Academy in Annapolis, and Baylor College of Medicine in Houston, 1979. He had graduate training in Immunology and malaria with Dr. Paul-Henri Lambert at the World Health Organization, Geneva, Switzerland from 1978-79, and post-doctoral training in transplantation biology with E. Donnell Thomas and John Hansen at the Fred Hutchinson Cancer Research Center in Seattle from 1983 - 1986. He is board certified in Internal Medicine and Medical Oncology. He maintains a research laboratory that studies various mechanisms of lymphocyte activation that relate to immune tolerance and adoptive immunotherapy for cancer and chronic infection. In 2011, his research team published findings detailing a new therapy in which patients with refractory and relapsed chronic lymphocytic leukemia were treated with genetically engineered versions of their own T cells. The treatment has also now also been used with promising results to treat children with refractory acute lymphoblastic leukemia. He has published more than 350 manuscripts and is the recipient of numerous prizes and honors, including election to the Institute of Medicine in 2012 and the American Academy of Arts and Sciences in 2014, the William B Coley award, the Richard V Smalley Memorial Award from the Society for Immunotherapy of Cancer, the AACR-CRI Lloyd J. Old Award in Cancer Immunology, the Philadelphia Award in 2012, the Taubman Prize for Excellence in Translational Medical Science in 2014 (shared with S. Grupp, B. Levine, D. Porter), the Paul Ehrlich and Ludwig Darmstaedter Prize (shared w J. Allison), the Novartis Prize in Immunology (shared with Z. Eshaar and S. Rosenberg), the Karl Landsteiner Memorial award, the Debrecen Award and a lifetime achievement award from the Leukemia and Lymphoma Society. For more information go to https://oir.nih.gov/wals Author: Carl June, M.D., Richard W. Vague Professor in Immunotherapy and Director of the Center for Cellular Immunotherapies at the Perelman School of Medicine; Director of the Parker Institute for Cancer Immunotherapy at the University of Pennsylvania Permanent link: https://videocast.nih.gov/launch.asp?19892
Views: 8266 nihvcast
Dynamics of PKA Signaling
 
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Air date: Wednesday, March 03, 2010, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Dr. Taylor's research led to solving the crystal structure of the first protein kinase in 1991, providing a template for this entire family of essential regulatory enzymes. Understanding the molecular basis for function, visualizing this one protein kinase and its structure, function and dynamics and translating that information to other related protein kinases continues to provide an ideal interdisciplinary system for coupling technological advances in computation and biophysics with exciting biological questions. She is a member of the National Academy of Sciences, American Academy of Arts and Sciences, Institute of Medicine, Howard Hughes Medical Institute, a fellow of the American Academy of Arts & Sciences, and a Fellow of the American Association for the Advancement of Sciences. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Author: Dr. Susan Taylor Runtime: 00:58:38 Permanent link: http://videocast.nih.gov/launch.asp?15658
Views: 1164 nihvcast
Using human stem cells to understand and treat diabetes
 
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Using human stem cells to understand and treat diabetes Air date: Thursday, December 15, 2016, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 00:57:19 Description: NIH Director's Wednesday Afternoon Lecture Series One goal of regenerative medicine is to replace missing or dysfunctional cells in patients. The Melton lab has pursued this goal for diabetics, focusing on the possibility of turning human stem cells into functional pancreatic beta cells, the cells that sense glucose and provide just the right amount of insulin. People with either Type 1 (juvenile) or Type 2 diabetes could benefit from the availability of an unlimited supply of functional beta cells. In this lecture, Dr. Melton will discuss the challenges of and progress in producing functional beta cells and point to the way forward on transplanting those cells into patients. For more information go to https://oir.nih.gov/wals Author: Douglas A. Melton, Ph.D., Xander University Professor at Harvard University; Co-Director of the Harvard Stem Cell Institute; Investigator, Howard Hughes Medical Institute Permanent link: https://videocast.nih.gov/launch.asp?21062
Views: 2405 nihvcast
Demystifying Medicine 2014 - Obesity: Etiology, Pathogenesis and Why Weight Loss is Difficult
 
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Demystifying Medicine 2014 - Obesity: Etiology, Pathogenesis and Why Weight Loss is Difficult Air date: Tuesday, February 04, 2014, 4:00:00 PM Runtime: 01:51:29 The 2014 Demystifying Medicine Series, which is jointly sponsored by FAES and NIH, will begin January 7th and includes the presentation of patients, pathology, diagnosis and therapy in the context of major disease problems and current research. Primarily directed toward Ph.D. students, clinicians and program managers, the course is designed to help bridge the gap between advances in biology and their application to major human diseases. Each session includes clinical and basic science components presented by NIH staff and invitees. All students, fellows and staff are welcome, as well. For more information go to http://demystifyingmedicine.od.nih.gov Author: Jack Yanovski, MD, PhD (NICHD) Kevin Hall, PhD (NIDDK) Permanent link: http://videocast.nih.gov/launch.asp?18266
Views: 2948 nihvcast
The mammalian virome in genetic analysis of health and disease pathogenesis
 
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The mammalian virome in genetic analysis of health and disease pathogenesis Air date: Wednesday, April 22, 2015, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:13:51 Description: The Annual R. E. Dyer Lecture Disease occurs in only some people carrying risk alleles, a phenomenon that may well be due in part to the influence of our virome. Chronic virus infection of mice protects the host against cancer and infection through symbiotic stimulation of innate immunity, and can complement multiple genetic immunodeficiencies. The virome may contribute to individual variations in the clinical presentation of disease. However, persistent viruses can also trigger "virus-plus-susceptibility-gene" interactions leading to bacteria-dependent inflammatory disease. These bacteria-dependent phenotypes are only observed when the virus and a mutant allele of a host gene are present at the same time. Virgin hypothesized that trans-kingdom metagenomic (viruses, bacteria, archaea, fungi, metazoans) interactions may regulate virus infection, immunity, and inflammation. His lab confirmed this hypothesis by showing that helminth infection can reactivate latent herpesvirus through cytokine competition between IFN-gamma and IL-4/IL-13 at a viral promoter, and can inhibit antiviral immunity. The Virgin lab recently found that antibiotic treatment prevents persistent enteric norovirus infection, an effect rescued by fecal transplantation. This effect requires the IFN-lambda receptor but not adaptive immunity. Furthermore, treatment with IFN-lambda cures persistent enteric norovirus infection in the absence of adaptive immune cells, documenting the existence of what we believe to be sterilizing innate anti-viral immunity. These data beg the question of whether the virome is associated with human disease. His lab has found that the enteric virome is abnormal in both Crohn's disease and ulcerative colitis. They also observed significant disease-specific increases in Caudovirales taxa despite detecting expected decreases in bacterial microbiome diversity. This obesvation is consistent with a predator-prey relationship between the enteric virome and the bacterial microbiome in these diseases. Together these data indicate that mammals are best viewed as composite organisms in which the virome, and trans-kingdom interactions regulating and regulated by the virome, contribute to immunity, disease, and the genotype-phenotype relationship. Genetic analysis of disease risk, and the study of normal immunity, should incorporate consideration of the virome and trans-kingdom metagenomic interactions that control the virome. About the annual Rolla E. Dyer lecture: The annual Rolla E. Dyer Lecture features an internationally renowned researcher who has contributed substantially to the medical as well as the biological knowledge of infectious diseases. Established in 1950, the lecture series honors former NIH director Dr. R. E. Dyer, who was a noted authority on infectious diseases. For more information go to http://wals.od.nih.gov Author: Herbert W. 'Skip' Virgin IV, M.D., Ph.D., Edward Mallinckrodt Professor and Chair Department of Pathology and Immunology, Professor of Molecular Microbiology, and Professor of Medicine at Washington University School of Medicine Permanent link: http://videocast.nih.gov/launch.asp?18963
Views: 8557 nihvcast
Protein Folding: Seeing is Deceiving
 
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Air date: Wednesday, September 15, 2010, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: The protein folding problem was first recognized by Hsien Wu (1931) and Mirsky & Pauling (1936), approximately three-quarters of a century ago. The problem ‑‑ arguably the most significant unsolved problem in chemical biology ‑‑ is inherently grounded in protein thermodynamics, and thermodynamics is surely our most powerful discipline for understanding biological systems. So why does fundamental understanding of protein folding remain an unresolved question? In work at the NIH, Anfinsen showed that a protein's three-dimensional structure is a spontaneous consequence of its amino acid sequence in water at physiological temperature and pressure. Remarkably, under dilute solution conditions, a purified protein adopts its native fold without either the addition of energy or assistance from auxiliary cellular components (chaperones notwithstanding). The fold of the protein links the one‑dimensional, linear world of DNA to the three-dimensional world of biological function; accordingly, protein folding is a cornerstone of life on earth. Yet, in essence, this self-assembly process lies within the province of biophysics, not cell biology. The classic folding paradigm, established by Anfinsen and others, has been interpreted to mean that under folding conditions, the native fold is selected from an astronomical number of conceivable alternatives by the constellation of favorable interactions between and among its amino acid sidechains. This plausible idea is entirely consistent with the characteristic close-packing seen in protein crystal structures, where it is apparent that residues distant in sequence are juxtaposed in space, presumably providing both structural stability and topological specificity. Contrary to this view, I will discuss evidence from both experiment and simulations that the overall fold is established prior to eventual sidechain close-packing. Consequently, formation of the folded, hydrogen-bonded framework and its further stabilization via sidechain locking are separable folding events, an enormously simplifying realization. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Author: Dr. George Rose Runtime: 01:19:36 Permanent link: http://videocast.nih.gov/launch.asp?16130
Views: 24871 nihvcast
IPPCR 2015: Overview of Clinical Study Design
 
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IPPCR 2015: Overview of Clinical Study Design Air date: Tuesday, October 20, 2015, 5:00:00 PM Category: IPPCR Runtime: 01:29:48 Description: The Introduction to the Principles and Practice of Clinical Research (IPPCR) is a course to train participants on how to effectively conduct clinical research. The course focuses on the spectrum of clinical research and the research process by highlighting epidemiologic methods, study design, protocol preparation, patient monitoring, quality assurance, and Food and Drug Administration (FDA) issues. For more information go to https://ippcr.nihtraining.com/login.php Author: Laura Lee Johnson, Ph.D., FDA Permanent link: http://videocast.nih.gov/launch.asp?19257
Views: 12378 nihvcast
The Epigenetic Basis of Common Human Disease
 
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The Epigenetic Basis of Common Human Disease Air date: Wednesday, September 03, 2014, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 00:59:42 Description: Wednesday Afternoon Lecture Series Although epigenetic changes in the cancer genome have been known for three decades, the role of epigenetics in common human disease and its relationship to genetic variation has only recently begun to be explored. The Feinberg lab has been developing whole-genome approaches to the epigenetic analysis of human disease and contributing to a new field of epigenetic epidemiology that integrates genetic, epigenetic, and environmental factors. One of the most exciting developments in this recent work is the idea that epigenetic plasticity under genetic control may confer a survival advantage in evolution, and may also be important in normal tissue differentiation and response to the environment. Dr. Feinberg has suggested a unifying model of cancer in which epigenetic dysregulation allows rapid selection for tumor cell survival at the expense of the host. For more information go to http://wals.od.nih.gov Author: Andrew P. Feinberg, M.P.H., M.D., Gilman Scholar and Professor of Medicine Director, Center for Epigenetics, Johns Hopkins University School of Medicine Permanent link: http://videocast.nih.gov/launch.asp?18582
Views: 11014 nihvcast
Measuring and Modeling Life-Death Decisions in Single Cells
 
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Air date: Wednesday, October 20, 2010, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Lecture Summary: When monitoring signal transduction at the level of single living cells, we observe remarkably complex dynamics and great variability from one cell to the next. However, it is also clear that finely tuned interactions among processes operating on quite different time scales are essential in cell fate determination and, conversely, that errors in coordination underlie many oncogenic changes. How can the observed variability among genetically identical cells be reconciled with an apparent requirement for precise control, what is the impact of variability on the evolution of tumors and what are the implications for emergence of drug resistant cancers in patients? I will begin to address these issues with an emphasis on cellular responses to TRAIL, a prototypical inducer of receptor-mediated (extrinsic) apoptosis and an investigational therapeutic. Some TRAIL-treated human cells die within ~40 min, some only after 12 hr, and yet others live indefinitely. We have explored three explanations for these differences: (i) genetic or epigenetic variation (ii) the involvement of one or more biochemical processes subject to stochastic fluctuation (iii) transient but deterministic differences in cell state. I will illustrate how all three interact on different time scales to determine those aspects of cellular physiology that are highly invariant and those that are variable. I will also illustrate how studying these problems requires mathematical analysis of the underlying biochemistry. This analysis involves a close interplay between model generation, model calibration against data and model verification through empirical testing of molecular hypotheses. I will advance the thesis that we must replace the informal pictorial models currently dominating molecular biology with probabilistic mathematical constructs that assign rigorous "degrees of belief" to specific biochemical hypothesis given prior knowledge and a specific set of empirical data. Lecture Objectives: 1. To describe an approach to understanding signal transduction pathways that involves combining biochemical and cell-based measurement with mathematical modeling of relevant molecular processes. In my lecture the focus will be on receptor-mediated cell death triggered by TRAIL and Fas ligands 2. To present an analysis of variability from one cell to the next in responses to TRAIL and our determination that this variability has a non-genetic basis, arising from natural fluctuations in protein levels among otherwise non-identical cells. 3. To consider the impact of non-genetic variability on responses to therapeutic drugs more generally and on the likely connection between variability and fractional killing observed clinically. To advance the idea that non-genetic variability, having its origins in the inherently stochastic nature of biochemical reactions, is a probable explanation for many phenomena currently ascribed to tumor stem cells. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Author: Dr. Peter Sorger, Harvard Medical School Runtime: 01:09:00 Permanent link: http://videocast.nih.gov/launch.asp?16220
Views: 2743 nihvcast
Ancient DNA and the new science of the human past
 
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Ancient DNA and the new science of the human past Air date: Wednesday, September 21, 2016, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:05:46 Description: NIH Director's Wednesday Afternoon Lecture Beginning in 2010, it became practical to sequence whole genomes from DNA extracted from ancient human boness, and to analyze the data to understand changes in biology over time. Since that timethen, the amount of ancient DNA data has increased at an extraordinary rate, with the number of samples with at least one-fold genome coverage being 5 five in 2013, 18 in 2014, and 116 in 2015. Dr. Reich will begin his lecture by describing how present-day Europeans derive from a fusion highly divergent ancestral populations as different from each other as are Europeans and East Asians. He will then summarize the history of modern humans in Europe over the approximately 45,000 years since they first arrived. He will next describe the spread of farming populations from the Near East over the last twelve thousands12,000 years. He will finally conclude by describing explaining how the analysis of ancient DNA has led to. some of the insights about human biological change over time. For more information go to https://oir.nih.gov/wals/2016-2017/ancient-dna-new-science-human-past Author: David Reich, D. Phil., Professor of Genetics Investigator, Howard Hughes Medical Institute, Harvard Medical School Permanent link: https://videocast.nih.gov/launch.asp?19875
Views: 42173 nihvcast
Epigenetics: How Genes and Environment Interact
 
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Epigenetics: How Genes and Environment Interact Air date: Wednesday, April 18, 2012, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Human epidemiological and animal experimental data indicate that the risk of developing adult onset diseases and neurological disorders is influenced by persistent adaptations to prenatal and early postnatal environmental exposures. One group of epigenetically regulated genes that potentially links environmental exposures early in development to adult diseases are those with metastable epialleles. These genes have highly variable expression because of stochastic allelic changes in the epigenome rather than mutations in the genome. The viable yellow agouti (Avy) mouse harbors a metastable Agouti gene because of an upstream insertion of a transposable element. We have used the Avy mouse to investigate the importance of epigenetic alterations in determining adult disease risk in response to early developmental exposure to both chemical and physical agents. The importance these studies with regards to human health and disease will be discussed. The NIH Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. For more information, visit: The NIH Director's Wednesday Afternoon Lecture Series Author: Randy Jirtle, Ph.D., Duke University Runtime: 00:58:00 Permanent link: http://videocast.nih.gov/launch.asp?17223
Views: 27434 nihvcast
The 3D genome organization and long-range control of gene expression
 
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The 3D genome organization and long-range control of gene expression Air date: Wednesday, February 03, 2016, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:00:35 Description: NIH Director’s Wednesday Afternoon Lecture Series The 3-dimensional (3D) genome organization plays an essential role in orchestrating many essential nuclear processes, including DNA replication, transcription, and repair of DNA damages. Great strides have been made recently in the study of 3D chromatin architecture in mammalian cells, with the development of technologies for genome-wide analysis of chromatin interactions at increasing precision and concepts such as "chromosome territories," "topologically associating domains," and "chromatin loops". For his lecture, Dr. Ren will discuss how these advances are transforming the study of gene regulatory mechanisms in mammalian cells. He will give specific examples that illustrate the role of 3D chromatin organization in developing revolutionary tools in sequencing diploid genomes; elucidate the molecular basis of genetic disorders caused by genome structural variations; and offer a functional characterization of enhancers, a class of gene regulatory sequences that can activate target genes at a large genomic distance. The dysfunction of enhancers has been implicated in the etiology of cancer, diabetes, and a broad spectrum of other human diseases. For more information go to https://oir.nih.gov/wals Author: Bing Ren, Ph.D., Ludwig Institute for Cancer Research, University of California, San Diego Permanent link: http://videocast.nih.gov/launch.asp?19464
Views: 6100 nihvcast
Genome regulation by long noncoding RNAs
 
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Genome regulation by long noncoding RNAs Air date: Wednesday, June 1, 2016, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:03:47 Description: NIH Director’s Wednesday Afternoon Lecture Series Dr. Chang’s research addresses how large sets of genes are turned on or off together, which is important in normal development, cancer, and aging. Chang discovered a new class of genes, termed long noncoding RNAs, can control gene activity throughout the genome, illuminating a new layer of biological regulation. He has invented new methods for defining the shapes of RNA and DNA genome-wide. The long term goal of his research is to decipher the regulatory information in the genome to benefit human health. For more information go to https://oir.nih.gov/wals Author: Howard Y. Chang, M.D., Ph.D., Stanford University Permanent link: http://videocast.nih.gov/launch.asp?19718
Views: 5341 nihvcast
The depressed brain: sobering and hopeful lessons
 
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The depressed brain: sobering and hopeful lessons Air date: Wednesday, June 10, 2015, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:03:33 Description: NIH Director’s Wednesday Afternoon Lecture In her talk, Dr. Akil will discuss the challenges of understanding the pathophysiology of major depressive disorder at the molecular and cellular level and the surprising insights derived from genomics and human postmortem studies. She will describe how animal models and neuroscience studies at multiple levels (from genetic to behaviorial) can be used to test and validate new targets for treatment and/or as biomarkers of the illness. Her talk will also focus on the notion of "molecular organizers" that play a broad role in neuroplasticity, development, adaptation to the environment, and responsiveness to treatment. For more information go to https://oir.nih.gov/wals Author: Huda Akil, Ph.D., Gardner Quarton Distinguished University Professor of Neuroscience and Psychiatry, Co-Director of the Molecular and Behavioral Neuroscience Institute, University of Michigan Permanent link: http://videocast.nih.gov/launch.asp?19057
Views: 2312 nihvcast
The epigenetic clock, biological age, and chronic diseases
 
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The epigenetic clock, biological age, and chronic diseases Air date: Wednesday, June 15, 2016, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:03:40 Description: NIH Director’s Wednesday Afternoon Lecture Series It has been a long standing goal to develop molecular biomarkers of biological age. Recent studies demonstrate that powerful epigenetic biomarkers of aging can be defined based on DNA methylation levels. For example, the epigenetic clock (PMID: 24138928) is a multivariate age estimation method that applies to sorted cell types (CD4T cells or neurons), complex tissues, and organs and even prenatal brain samples. The epigenetic clock is an attractive biomarker of aging because a) it applies to most human and chimpanzee tissues, b) its accurate measurement of chronological age is unprecedented, c) it is predictive of all-cause mortality even after adjusting for a variety of known risk factors, d) it correlates with measures of cognitive and physical fitness in the elderly, and e) it has been found useful for detecting accelerated aging effects due to obesity, Down syndrome, and HIV infection. Recent genomewide association studies shed light on the underlying biological mechanisms. For more information go to https://oir.nih.gov/wals Author: Steve Horvath, Sc.D., Ph.D., University of California, Los Angeles Permanent link: http://videocast.nih.gov/launch.asp?19753
Views: 5303 nihvcast
New antibiotics from the microbial dark matter
 
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New antibiotics from the microbial dark matter Air date: Wednesday, February 15, 2017, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 00:58:16 Description: NIH Director's Wednesday Afternoon Lecture Series We are experiencing an antibiotic crisis: Our ability to discover novel compounds has diminished and pathogens go largely unchecked in acquiring and spreading resistance. The main source of antibiotics–soil actinomycetes–has been overmined. In chronic infections, the problem is compounded by the presence of dormant persister cells that are resistant to all antibiotics. As a result, chronic osteomyelitis or infections in patients with cystic fibrosis can be untreatable. About 99 percent of environmental microorganisms are uncultured. Dr. Lewis’s lab developed approaches for killing persister cells and growing uncultured bacteria. The lab found that this "microbial dark matter" harbors novel antimicrobials that evolved to be essentially free of resistance. For more information go to https://oir.nih.gov/wals/2016-2017 Author: Kim Lewis, Ph.D., Director, Antimicrobial Discovery Center, Northeastern University Permanent link: https://videocast.nih.gov/launch.asp?21138
Views: 1430 nihvcast
A Look at the Unconscious Brain Under General Anesthesia
 
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Air date: Wednesday, March 02, 2011, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: General anesthesia is a drug-induced, reversible condition comprised of five behavioral and physiological states: unconsciousness, amnesia (loss of memory), analgesia (loss of pain sensation), akinesia (immobility), and cardiovascular, respiratory and thermoregulatory stability with control of the stress response. The mechanisms by which anesthetic drugs induce the state of general anesthesia is considered one of the biggest mysteries of modern medicine. We have been using three experimental paradigms to study general anesthesia-induced loss of consciousness in humans: combined fMRI/EEG recordings, high-density EEG recordings and intracranial recordings. These studies are allowing us to establish precise neurophysiological, neuroanatomical and behavioral correlates of general anesthesia. We will discuss the relation between our findings and two other important altered states of arousal: sleep and coma. Our findings suggest that the state of general anesthesia is not as mysterious as currently believed. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Author: Dr. Emery Brown, Massachusetts Institute of Technology Runtime: 01:10:51 Permanent link: http://videocast.nih.gov/launch.asp?16502
Views: 17284 nihvcast
The future of genetic codes and BRAIN codes
 
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The future of genetic codes and BRAIN codes Air date: Wednesday, February 8, 2017, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:06:08 Description: Marshall W. Nirenberg Lecture This lecture, established in 2011, recognizes Marshall Nirenberg for his work to decipher the genetic code, which resulted in his receiving the 1968 Nobel Prize in Physiology or Medicine. Nirenberg's research career at the NIH spanned more than 50 years, and his research also focused on neuroscience, neural development, and the homeobox genes. The Nirenberg lecture recognizes outstanding contributions to genetics and molecular biology. Dr. Church is a professor of genetics at Harvard Medical School and director of PersonalGenomes.org, which provides the world's only open-access information on human genomic, environmental, and trait data (GET). His 1984 Harvard Ph.D. thesis included the first methods for direct genome sequencing, molecular multiplexing, and barcoding. These methods led to the first genome sequence (pathogen, Helicobacter pylori) in 1994. His innovations have contributed to nearly all "next generation" DNA sequencing methods and companies. These innovations plus his lab's work on chip-DNA-synthesis, gene editing, and stem cell engineering resulted in founding additional application-based companies spanning the fields of medical diagnostics and synthetic biology/therapeutics. He has also pioneered new privacy, biosafety, ELSI, environmental, and biosecurity policies. He is director of an IARPA BRAIN Project and the NIH Center for Excellence in Genomic Science. His honors include election to National Academy of Sciences and the National Academy of Engineering. He is also a Franklin Bower Laureate for Achievement in Science. He has co-authored 425 papers, 95 patent publications, and one book (Regenesis). Dr. Church's lecture will focus on transformative technologies moving at exponential rates for reading, writing and editing genomes, epigenomes, and other omes. Applications include cells resistant to all viruses via new genetic codes, production and analysis of organs for transplantation, and therapy testing. For more information go to https://oir.nih.gov/wals/2016-2017 Author: George M. Church, Ph.D., Professor of Genetics, Harvard Medical School Permanent link: https://videocast.nih.gov/launch.asp?21127
Views: 5384 nihvcast
Translational Bioinformatics: Transforming 300 Billion Points of Data
 
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Translational Bioinformatics: Transforming 300 Billion Points of Data into Diagnostics, Therapeutics, and New Insights into Disease Air date: Wednesday, June 20, 2012, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Description: There is an urgent need to translate genome-era discoveries into clinical utility, but the difficulties in making bench-to-bedside translations haven't been well described. The nascent field of translational bioinformatics may help. Dr. Butte's lab at Stanford University builds and applies tools that convert more than 300 billion points of molecular, clinical, and epidemiological data (measured by researchers and clinicians over the past decade) into diagnostics, therapeutics, and new insights into disease. Dr. Butte, a bioinformatician and pediatric endocrinologist, will highlight his lab's work on using publicly available molecular measurements to find new uses for drugs, discovering new treatable mechanisms of disease in type 2 diabetes, and evaluating patients presenting with whole genomes sequenced. The NIH Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. For more information, visit: The NIH Director's Wednesday Afternoon Lecture Series Author: Atul Butte, M.D., Ph.D., Stanford University Runtime: 01:07:42 Permanent link: http://videocast.nih.gov/launch.asp?17321
Views: 11932 nihvcast
Mitochondria: dynamic organelles critical for human health
 
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Mitochondria: dynamic organelles critical for human health Air date: Wednesday, October 03, 2012, 3:00:00 PM Description: Mitochondria are dynamic organelles that fuse, divide, and move. Human genetic studies indicate that these processes are important for normal functioning of tissues, particularly neurons. Mutations in Mitofusion-2 (Mfn2) cause peripheral neuropathy (Charcot-Marie-Tooth 2A), and mutations in optic atrophy 1 (OPA1) cause eye disease (dominant optic atrophy). Mouse knockout studies focused on the mitofusins Mfn1 and Mfn2 have shown that mitochondrial fusion is important for organellar function. Dr. Chan will discuss mouse studies that reveal the physiological functions of mitochondrial dynamics. In addition, Dr. Chan will discuss how new mouse models can be combined with imaging approaches to understand the role of mitochondrial dynamics in neurodegeneration. The NIH Director's Wednesday Afternoon Lecture Series, colloquially known as WALS, is the highest-profile lecture program at the NIH. Lectures occur on most Wednesdays from September through June from 3:00 to 4:00 p.m. in Masur Auditorium, Building 10 on the NIH Bethesda campus. Each season includes some of the biggest names in biomedical and behavioral research. The goal of the WALS is to keep NIH researchers abreast of the latest and most important research in the Unites States and beyond. An added treat is the annual J. Edward Rall Cultural Lecture, which features top authors and other cultural icons. All speakers are nominated by the NIH community. For more information, visit: The NIH Director's Wednesday Afternoon Lecture Series Author: David C. Chan, M.D., Ph.D., California Institute of Technology Runtime: 01:00:09 Permanent link: http://videocast.nih.gov/launch.asp?17600
Views: 12688 nihvcast
Leptin and the neural circuit regulation food intake and glucose metabolism
 
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Leptin and the neural circuit regulation food intake and glucose metabolism Air date: Wednesday, January 11, 2017, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 00:57:39 Description: NIH Director’s Wednesday Afternoon Lecture Series The discovery of leptin has led to the elucidation of a robust physiologic system that maintains fat stores at a relatively constant level. Leptin is a peptide hormone secreted by adipose tissue in proportion to its mass. This hormone circulates in blood and acts on the hypothalamus to regulate food intake and energy expenditure. When fat mass falls, plasma leptin levels fall stimulating appetite and suppressing energy expenditure until fat mass is restored. When fat mass increases, leptin levels increase, suppressing appetite until weight is lost. By such a mechanism, total energy stores are stably maintained within a relatively narrow range. Recessive mutations in the leptin gene are associated with massive obesity in mice and some humans. Treatment with recombinant leptin markedly reduces food intake and body weight. The low leptin levels in patients with leptin mutations are also associated with multiple abnormalities including infertility, diabetes, and immune abnormalities all of which are corrected by leptin treatment. These findings have established important links between energy stores and many other physiologic systems and led to the use of leptin as a treatment for an increasing number of other human conditions including a subset of obesity, some forms of diabetes including lipodystrophy and hypothalamic amenorrhea, the cessation of menstruation seen in extremely thin women. Identification of a physiologic system that controls energy balance establishes a biologic basis for obesity. Recent studies have explored the relationship between leptin and the reward value of food. In addition, new methods for identifying neurons activated by leptin and other stimuli have been developed as have methods for noninvasively activating cells using radio waves. These new approaches are being applied to studies of the neural processes that control feeding, a complex motivational behavior. For more information go to https://oir.nih.gov/wals Author: Jeffrey Friedman, M.D., Ph.D., Professor, The Rockefeller University; Director, Starr Center for Human Genetics; Investigator, Howard Hughes Medical Institute Permanent link: https://videocast.nih.gov/launch.asp?21075
Views: 7714 nihvcast
IPPCR 2015: Conceptual Approach to Survival Analysis
 
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IPPCR 2015: Conceptual Approach to Survival Analysis Air date: Monday, November 16, 2015, 5:00:00 PM Category: IPPCR Runtime: 01:30:11 Description: The Introduction to the Principles and Practice of Clinical Research (IPPCR) is a course to train participants on how to effectively conduct clinical research. The course focuses on the spectrum of clinical research and the research process by highlighting epidemiologic methods, study design, protocol preparation, patient monitoring, quality assurance, and Food and Drug Administration (FDA) issues. For more information go to https://ippcr.nihtraining.com/login.php Author: Laura Lee Johnson, Ph.D., FDA Permanent link: http://videocast.nih.gov/launch.asp?19321
Views: 16371 nihvcast
Epigenetic Genome Control by Heterochromatin and RNAi Machinery
 
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Air date: Wednesday, October 27, 2010, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Lecture Summary: Expression profiling of eukaryotic genomes has revealed widespread transcription outside the confines of protein-coding genes, leading to the production of antisense and non-coding RNAs. Studies in Schizosaccharomyces pombe and multicellular organisms suggest that transcription and non-coding RNAs provide a framework for the assembly of heterochromatin structures, which have been linked to various chromosomal processes. In addition to gene regulation, heterochromatin is critical for centromere function, cell fate determination as well as transcriptional and posttranscriptional silencing of repetitive DNA elements that are known to be major source of genomic instability. We have found that heterochromatin factors are widely distributed across euchromatic loci and collaborate with RNAi machinery to suppress antisense transcripts across large portions of the genome. Our recent progress in understanding the mechanisms of heterochromatin assembly, and the roles of RNAi and heterochromatin factors in epigenetic genome control will be discussed. Lecture Objectives: 1. Discuss roles of RNAi machinery and non-coding RNAs in heterochromatin assembly. 2. Roles of heterochromatin machinery in gene silencing and maintenance of genome stability. 3. Novel genome surveillance mechanisms essential for silencing retrotransposons. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Author: Dr. Shiv Grewal, Center for Cancer Research, National Cancer Institute Runtime: 01:02:34 Permanent link: http://videocast.nih.gov/launch.asp?16229
Views: 10748 nihvcast
Stem Cells, Aging & Aging Stem Cells
 
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Stem Cells, Aging & Aging Stem Cells Air date: Wednesday, April 5, 2017, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:03:33 Description: NIH Director’s Wednesday Afternoon Lecture Series A leader in the field of stem cell biology, Dr. Wagers has done groundbreaking research to uncover new migratory pathways and signaling networks that regulate the functioning of hematopoietic stem cells. Understanding how these cells function could lead to better treatments for a range of diseases including cancer, anemia, and diabetes. For her lecture, Dr. Wagers will discuss the fundamental principles that govern tissue aging and determine stem cell function in organ regeneration and degenerative disease. The annual Florence S. Mahoney Lecture on Aging is named in honor of Florence Stephenson Mahoney (1899–2002). She devoted the last half of her life to successfully advocating for the creation of the National Institute on Aging and increased support for the NIH. Amy Wagers, Ph.D., Forst Family Professor of Stem Cell and Regenerative Biology at Harvard University and Harvard Medical School, Senior Investigator, Joslin Diabetes Center and Principal Faculty, Harvard Stem Cell Institute Permanent link: https://videocast.nih.gov/launch.asp?23213
Views: 3343 nihvcast
Aquaporin water channels - from transfusion medicine to malaria
 
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Aquaporin water channels - from transfusion medicine to malaria Air date: Wednesday, September 09, 2015, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 00:57:37 Description: NIH Director’s Wednesday Afternoon Lecture Series Biochemical analysis of the Rhesus blood group antigen led to the serendipitous discovery of AQP1, the first molecular water channel. Found throughout nature, aquaporin water channels confer high water permeability to cell membranes. AQP1 has been characterized biophysically, and the atomic structure of AQP1 is known. Identification of the Colton blood group antigen on the extracellular domain of AQP1 allowed identification of rare individuals who are AQP1-null and manifest a subclinical form of nephrogenic diabetes insipidus. Thirteen homologous proteins exist in humans. Some transport only water (aquaporins); others transport water plus glycerol (aquaglyceroporins). These proteins are required for generation of physiological fluids (urine, cerebrospinal fluid, aqueous humor, sweat, saliva, and tears). Involvement of aquaporins in multiple clinical states is becoming recognized—renal concentration, fluid retention, blindness, skin hydration, brain edema, thermal stress, glucose homeostasis, malaria, and even arsenic poisoning. Aquaporins are particularly important in plant biology. This information now provides the challenge of developing new technologies to manipulate aquaporins for clinical or agricultural benefits. For more information go to https://oir.nih.gov/wals Author: Peter Agre, M.D., Johns Hopkins Malaria Research Institute Permanent link: http://videocast.nih.gov/launch.asp?19139
Views: 457 nihvcast
Biomedical research: increasing value, reducing waste
 
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Biomedical research: increasing value, reducing waste Air date: Wednesday, April 20, 2016, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:00:55 Description: NIH Director’s Wednesday Afternoon Lecture Series More than $200 billion is spent worldwide annually on biomedical research but estimates suggest as much as 85 percent may be wasted. What are the determinants of research waste and is such a high figure justified? A series of five papers in The Lancet (January 8, 2014) introduced this topics in detail and is updated in this lecture. This presentation focuses on redundancy and duplication of research hypotheses, research designs that cannot reliably test hypotheses, publication bias, and irreproducibility. Solutions for reducing waste and increasing value are discussed. For more information go to https://oir.nih.gov/wals Author: Michael B. Bracken, Ph.D., MPH, FACE, Yale School of Public Health Permanent link: http://videocast.nih.gov/launch.asp?19636
Views: 343 nihvcast
The Structural Basis of Ebola Viral Pathogenesis
 
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The Structural Basis of Ebola Viral Pathogenesis Air date: Wednesday, November 06, 2013, 3:00:00 PM Description: The Wednesday Afternoon Lecture Series presents the NIH Director's Lecture Dr. Saphire's lab studies viruses with compact genomes that encode just four to seven genes each. Viruses with limited genomes offer a defined landscape of possible protein-protein interactions. Each protein is critical-many are obligated to perform multiple functions and some rearrange their structures to achieve those new functions. As a result, these few polypeptides accomplish a surprisingly complex set of biological functions including immune evasion, receptor recognition, cell entry, transcription, translation, assembly and exit. Dr. Saphire systematically analyzes the structures and functions of each protein encodes by the virus to gain fundamental insights into the biology of entry, immune evasion, and assembly, and to decipher the collaborative roles of these proteins in pathogenesis. In this lecture, Dr. Saphire will illustrate the molecular function throughout the viral life cycle: how the Ebola virus glycoprotein remodels itself during viral entry and how this remodeling affects the antibody response; how the Ebola and Lassa viruses suppress host innate immune signaling; and how the Ebola matrix protein assembles into one structure to bud new virions and into a different conformation to bind RNA and control transcription inside infected cells. For more information go to http://wals.od.nih.gov Author: Erica Ollmann Saphire, Ph.D., Professor, Department of Immunology and Microbial Science, The Scripps Research Institute Runtime: 00:55:40 Permanent link: http://videocast.nih.gov/launch.asp?18151
Views: 16863 nihvcast
Computational Biology in the 21st Century: Making Sense out of Massive Data
 
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Computational Biology in the 21st Century: Making Sense out of Massive Data Air date: Wednesday, February 01, 2012, 3:00:00 PM Category: Wednesday Afternoon Lectures Description: The last two decades have seen an exponential increase in genomic and biomedical data, which will soon outstrip advances in computing power to perform current methods of analysis. Extracting new science from these massive datasets will require not only faster computers; it will require smarter algorithms. We show how ideas from cutting-edge algorithms, including spectral graph theory and modern data structures, can be used to attack challenges in sequencing, medical genomics and biological networks. The NIH Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Author: Dr. Bonnie Berger Runtime: 00:58:06 Permanent link: http://videocast.nih.gov/launch.asp?17563
Views: 4956 nihvcast
From microbial immunity to genome editing
 
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From microbial immunity to genome editing Air date: Wednesday, June 28, 2017, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:06:44 Description: NIH Director's Wednesday Afternoon Lecture Series The microbial CRISPR-Cas adaptive immune systems provide archaea and bacteria with a programmable defense against invading nucleic acids. Several years ago, Dr. Zhang and others reported that the effector module from Streptococcus pyogenes CRISPR-Cas9 (SpCas9) could be harnessed for genome editing. Following this work, Zhang's lab has discovered, characterized, and engineered additional Cas enyzmes for use as molecular biology tools. These include a novel class of CRISPR-Cas systems that use RNA-guided RNases, such as Cas13a (C2c2) and Cas13b. Leveraging the natural properties of Cas13a, the lab developed a single-molecule nucleic acid sensing platform termed SHERLOCK, which can be used for rapid pathogen detection and genotyping. Zhang is continuing to explore microbial diversity to identify novel enzymes and systems that could serve as the basis for the development of additional molecular biology tools and applying these tools to tackle complex biological questions.. For more information go to https://oir.nih.gov/wals Author: Feng Zhang, Ph.D., Core Member, The Broad Institute of MIT; Investigator, McGovern Institute for Brain Research; Associate Professor, Departments of Brain and Cognitive Sciences and Biological Engineering, Massachusetts Institute of Technology Permanent link: https://videocast.nih.gov/launch.asp?23381
Views: 6011 nihvcast
Toward a Universal Influenza Virus Vaccine
 
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Toward a Universal Influenza Virus Vaccine Air date: Wednesday, April 30, 2014, 3:00:00 PM Category: Wednesday Afternoon Lectures Runtime: 00:51:42 Description: Wednesday Afternoon Lecture Series Because influenza viruses are constantly changing, it's difficult to develop effective vaccines against them. Two molecules on the surface of the virus control its infectivity: hemagglutinin and neuraminidase. Current influenza virus vaccines predominantly elicit a protective immune response to the immunodominant but variable head of the hemagglutinin. This approach is effective, especially when the vaccine strain closely matches the circulating virus. Another vaccine strategy involves redirecting the response to the more conserved stalk domain of the hemagglutinin and the immunosubdominant neuraminidase. This can be achieved by using vaccine strains that express chimeric hemagglutinin proteins whereby the head of the hemagglutinin represents an exotic subtype never encountered by humans under natural conditions. Such influenza virus constructs are likely to boost memory B-cells directed against conserved epitopes of the hemagglutinin stalk and the neuraminidase, and thus should afford broad spectrum protection against a variety of antigenic drift and shift strains. For more information go to http://wals.od.nih.gov Author: Peter Palese, Ph.D., Professor and Chair, Department of Microbiology, Mount Sinai School of Medicine Permanent link: http://videocast.nih.gov/launch.asp?18409
Views: 1619 nihvcast
Perspective on autoimmunity: a view from the ANCA vasculitis looking glass
 
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Perspective on autoimmunity: a view from the ANCA vasculitis looking glass Air date: Wednesday, November 2, 2016, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 00:59:24 Description: NIH Director's Wednesday Afternoon Lecture Astute Clinician Lecture Dr. Falk's research probes questions focused on immune-mediated kidney diseases, especially glomerulonephritis. His clinical and basic science interests include both anti-neutrophil cytoplasmic autoantibody (ANCA) glomerulonephritis and small vessel vasculitis (SVV). A central objective of Falk's research is elucidating the causes of ANCA necrotizing and crescentic glomerulonephritis. Unraveling the cause of this disease requires considering a number of factors involved in the development of ANCA glomerulonephritis. Dr. Falk conceptualizes this process as opening the vasculitis lock with a key that has a number of "ridges and valleys" analogous to those factors that contribute to the development of this autoimmune disease. Dr. Falk participates in a research group that, in a large study over the last four years, has revealed a number of avenues of investigation and new approaches to ongoing questions that pertain not only to ANCA glomerulonephritis, but to the general fields of autoimmunity, inflammation and basic neutrophil and monocyte biology. This annual lecture started in 1998 and honors a U.S. scientist who has observed an unusual occurrence, and by investigating it, has opened an important new avenue of research. The lectureship exemplifies how astute clinical observations can lead to innovative research. Speakers are selected by the NIH Clinical Center. For more information go to https://oir.nih.gov/wals/2016-2017 Debug: Show Debug Author: Ronald J. Falk, M.D., Hugh and Nan Cullman Eminent Professor and Chair, Department of Medicine at University of North Carolina - Chapel Hill Permanent link: https://videocast.nih.gov/launch.asp?19984
Views: 1204 nihvcast
Molecular Chaperones in Protein Folding and Neurodegeneration
 
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Air date: Wednesday, January 27, 2010, 3:00:00 PM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Lecture Objectives: 1. Explain the biological function of molecular chaperones, in particular the chaperonin ring class of chaperones. 2. Explain the mechanism of action of chaperonins, including the nature of their use of ATP. 3. Discuss studies of protein misfolding and neurodegenerative disease, relating the action of chaperones in one such condition. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Author: Arthur Horwich, M.D., Yale School of Medicine Runtime: 01:06:47 Permanent link: http://videocast.nih.gov/launch.asp?15583
Views: 35684 nihvcast
From the 'Genetic Code' to the 'Genetic Code'
 
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Air date: Friday, May 20, 2011, 11:30:00 AM Time displayed is Eastern Time, Washington DC Local Category: Wednesday Afternoon Lectures Description: Annual Marshall Nirenberg Lecture - 2011 The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. Eric Lander , Ph.D., President and Director of the Broad Institute of Harvard and MIT, Professor of Biology at MIT and Professor of Systems Biology at Harvard, will present the first annual Marshall Nirenberg Lecture on May 20, 2011. "From the 'Genetic Code' to the 'Genetic Code'" Author: Eric Lander , Ph.D., President and Director of the Broad Institute of Harvard and MIT Runtime: 01:23:00 Permanent link: http://videocast.nih.gov/launch.asp?16668
Views: 3161 nihvcast
Thinking about cancer as an infectious disease
 
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Thinking about cancer as an infectious disease Air date: Wednesday, May 31, 2017, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 00:47:33 Description: The Wednesday Afternoon Lecture Series presents the annual George Khoury Lecture Infection causes one in five cancers throughout the world. Why do just seven human viruses cause cancer, but not others? Merkel cell polyomavirus (MCV), the recently discovered cause of Merkel cell carcinoma (a rare type of skin cancer), provides clues on how viruses can cause cancer as well as insights into cancers that are not caused by infection. Tumor-virus studies reveal a fundamental duality between antiviral defenses and tumor suppression. MCV is an example in which mutations to our viral flora, not to the host cells themselves, help to turn this innocuous agent into the cause for the most aggressive skin cancer. MCV also reveals how a small virus, composed of just a few genes, can persist and successfully evade the immune system for decades. This feature has importance not only for viral cancers but also may give clues to other chronic viral infections. About the Khoury lecture: Organized by NIH scientists to honor the memory of cancer virologist George Khoury, M.D., who was highly regarded as a superb scientist and caring mentor of the postdoctoral fellows in his laboratory. Dr. Khoury, former chief of the Laboratory of Molecular Virology at the National Cancer Institute, was known for his instinctive inquisitive nature, unfaltering kindness, self-giving mentorship, and exceptional science. For more information go to https://oir.nih.gov/wals/2016-2017 Author: Patrick Moore, M.D., M.P.H., Distinguished and American Cancer Society Professor at University of Pittsburgh Cancer Institute Permanent link: https://videocast.nih.gov/launch.asp?23328
Views: 968 nihvcast
IPPCR 2015: Overview of Hypothesis Testing
 
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IPPCR 2015: Overview of Hypothesis Testing Air date: Tuesday, November 03, 2015, 5:00:00 PM Category: IPPCR Runtime: 01:27:08 Description: The Introduction to the Principles and Practice of Clinical Research (IPPCR) is a course to train participants on how to effectively conduct clinical research. The course focuses on the spectrum of clinical research and the research process by highlighting epidemiologic methods, study design, protocol preparation, patient monitoring, quality assurance, and Food and Drug Administration (FDA) issues. For more information go to https://ippcr.nihtraining.com/login.php Author: Paul Wakim, Ph.D., NIH Permanent link: http://videocast.nih.gov/launch.asp?19299
Views: 4383 nihvcast
IPPCR: The Clinical Researcher and the Media
 
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IPPCR: The Clinical Researcher and the Media Air date: Tuesday, March 22, 2016, 5:00:00 PM Category: IPPCR Runtime: 00:27:43 Description: The Introduction to the Principles and Practice of Clinical Research (IPPCR) is a course to train participants on how to effectively conduct clinical research. The course focuses on the spectrum of clinical research and the research process by highlighting epidemiologic methods, study design, protocol preparation, patient monitoring, quality assurance, and Food and Drug Administration (FDA) issues. For more information go to http://clinicalcenter.nih.gov/training/training/ippcr1.html Author: John Burklow, M.S., NIH Permanent link: http://videocast.nih.gov/launch.asp?19566
Views: 937 nihvcast
Epigenetic Regulation of Senescence and Aging
 
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Epigenetic Regulation of Senescence and Aging Air date: Wednesday, March 12, 2014, 3:00:00 PM Category: Wednesday Afternoon Lectures Runtime: 01:08:10 Description: Wednesday Afternoon Lecture Series The Annual Florence Mahoney Lecture Aging is a crucial risk factor in a constellation of human diseases, including cancer and neurodegeneration. Along with other risk factors such as environmental exposures, diet, behavior and heredity, these risks can be understood through their impact on the epigenetic landscape in ways that ultimately lead to the burden of disease. Among these risks, aging had been regarded as fixed, but current thinking holds that aging is plastic and its pace can be slowed or even reversed. Dr. Berger's laboratory has been studying the causal roles of epigenetics in aging, focused on structural features of chromatin and gene regulation in relation to senescence. These studies of the epigenetic landscape of senescent cells reveal profound alterations both in genome-wide transcription and histone post-translational modifications (which help regulate the structure of chromatin). Most of the epigenetic changes cover broad domains of the genome, and the locations and underlying gene regulatory changes indicate that, on one hand, oncogenic escape results from induction of specific genes that regulate pluripotency, while on the other hand aging-related alterations are caused by mutations that accumulate over "open domains" in chromatin after many cell replications. These findings provide a broad view of the relationship between aging and disease. Further, the chromatin changes lead to profound implications for potential epigenetic therapeutics to address diseases of aging. For more information go to http://wals.od.nih.gov Author: Dr. Shelley Berger, Perelman School of Medicine at the University of Pennsylvania Permanent link: http://videocast.nih.gov/launch.asp?18326
Views: 11545 nihvcast