Cold Spring Harbor perspectives in medicine This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

[PERSPECTIVES] Mouse Models in the Study of Mature B-Cell Malignancies
Over the past two decades, genomic analyses of several B-cell lymphoma entities have identified a large number of genes that are recurrently mutated, suggesting that their aberrant function promotes lymphomagenesis. For many of those genes, the specific role in normal B-cell development is unknown; moreover, whether and how their deregulated activity contributes to lymphoma initiation and/or maintenance is often difficult to determine. Genetically engineered mouse models that faithfully mimic lymphoma-associated genetic alterations represent valuable tools for elucidating the pathogenic roles of candidate oncogenes and tum...
Source: Cold Spring Harbor perspectives in medicine - April 1, 2021 Category: Research Authors: Pasqualucci, L., Klein, U. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights PERSPECTIVES Source Type: research

[PERSPECTIVES] Neonatal Opioid Withdrawal Syndrome (NOWS): A Transgenerational Echo of the Opioid Crisis
The incidence of neonatal opioid withdrawal syndrome (NOWS) has increased substantially in the setting of the opioid epidemic, a major public health problem in the United States. At present, NOWS has commonly used assessment and treatment protocols, but new protocols have questioned old practices. However, because of limited access to opioid use disorder (OUD) treatment and socioeconomic factors, many pregnant (and postpartum) women with OUD do not receive treatment. The pathophysiology of NOWS is not completely understood, although limited research studies have been conducted in humans and animals to better understand its...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2021 Category: Research Authors: Weller, A. E., Crist, R. C., Reiner, B. C., Doyle, G. A., Berrettini, W. H. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Glutamatergic Systems and Memory Mechanisms Underlying Opioid Addiction
Glutamate is the main excitatory neurotransmitter in the brain and is of critical importance for the synaptic and circuit mechanisms that underlie opioid addiction. Opioid memories formed over the course of repeated drug use and withdrawal can become powerful stimuli that trigger craving and relapse, and glutamatergic neurotransmission is essential for the formation and maintenance of these memories. In this review, we discuss the mechanisms by which glutamate, dopamine, and opioid signaling interact to mediate the primary rewarding effects of opioids, and cover the glutamatergic systems and circuits that mediate the expre...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2021 Category: Research Authors: Heinsbroek, J. A., De Vries, T. J., Peters, J. Tags: Addiction PERSPECTIVES Source Type: research

[TECHNIQUES] Integrating Family-Based and Mendelian Randomization Designs
Most Mendelian randomization (MR) studies published in the literature to date have involved analyses of unrelated, putatively independent sets of individuals. However, estimates obtained from these sorts of studies are subject to a range of biases including dynastic effects, assortative mating, residual population stratification, and horizontal pleiotropy. The inclusion of related individuals in MR studies can help control for and, in some cases, estimate the effect of these biases on causal parameters. In this review, we discuss these biases, how they can affect MR studies, and describe three sorts of family-based study d...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2021 Category: Research Authors: Hwang, L.-D., Davies, N. M., Warrington, N. M., Evans, D. M. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development TECHNIQUES Source Type: research

[TECHNIQUES] Family-Based Designs that Disentangle Inherited Factors from Pre- and Postnatal Environmental Exposures: In Vitro Fertilization, Discordant Sibling Pairs, Maternal versus Paternal Comparisons, and Adoption Designs
Identifying environmental risk and protective exposures that have causal effects on health is an important scientific goal. Many environmental exposures are nonrandomly allocated and influenced by dispositional factors including inherited ones. We review family-based designs that can separate the influence of environmental exposures from inherited influences shared between parent and offspring. We focus on prenatal exposures. We highlight that the family-based designs that can separate the prenatal environment from inherited confounds are different to those that are able to pull apart later-life environmental exposures fro...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2021 Category: Research Authors: Thapar, A., Rice, F. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development TECHNIQUES Source Type: research

[PERSPECTIVES] Swine Influenza A Viruses and the Tangled Relationship with Humans
Influenza A viruses (IAVs) are the causative agents of one of the most important viral respiratory diseases in pigs and humans. Human and swine IAV are prone to interspecies transmission, leading to regular incursions from human to pig and vice versa. This bidirectional transmission of IAV has heavily influenced the evolutionary history of IAV in both species. Transmission of distinct human seasonal lineages to pigs, followed by sustained within-host transmission and rapid adaptation and evolution, represent a considerable challenge for pig health and production. Consequently, although only subtypes of H1N1, H1N2, and H3N2...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2021 Category: Research Authors: Anderson, T. K., Chang, J., Arendsee, Z. W., Venkatesh, D., Souza, C. K., Kimble, J. B., Lewis, N. S., Davis, C. T., Vincent, A. L. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Immunity to Influenza Infection in Humans
This review discusses the human immune responses to influenza infection with some insights from studies using animal models, such as experimental infection of mice. Recent technological advances in the study of human immune responses have greatly added to our knowledge of the infection and immune responses, and therefore much of the focus is on recent studies that have moved the field forward. We consider the complexity of the adaptive response generated by many sequential encounters through infection and vaccination. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - March 1, 2021 Category: Research Authors: Topham, D. J., DeDiego, M. L., Nogales, A., Sangster, M. Y., Sant, A. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Antibody Responses in Hepatitis C Infection
Antibody responses in hepatitis C virus (HCV) have been a rather mysterious research topic for many investigators working in the field. Chronic HCV infection is often associated with dysregulation of immune functions particularly in B cells, leading to abnormal lymphoproliferation or the production of autoantibodies that exacerbate inflammation and extrahepatic diseases. When considering the antiviral function of antibody, it was difficult to endorse its role in HCV protection, whereas T-cell response has been shown unequivocally critical for natural recovery. Recent breakthroughs in the study of HCV and antigen-specific a...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2021 Category: Research Authors: Law, M. Tags: Hepatitis C Virus: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[RETROSPECTIVE] A History of Cancer Research: Carcinogens and Mutagens
Observations of the incidence of tumors among chimney sweeps in the eighteenth century and later experiments with coal tars provided early evidence that carcinogens in the environment can promote cancer. Subsequent studies of individuals exposed to radiation, work on fly genetics, and the discovery that DNA was the genetic material led to the idea that these carcinogens act by inducing mutations in DNA that change the behavior of cells and ultimately cause cancer. In this excerpt from his forthcoming book, Joe Lipsick looks back at how the concepts of mutagenesis and carcinogenesis emerged, how these converged with develop...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2021 Category: Research Authors: Lipsick, J. Tags: RETROSPECTIVE Source Type: research

[PERSPECTIVES] Non-Hodgkin Lymphomas: Malignancies Arising from Mature B Cells
Non-Hodgkin lymphomas (NHLs) are a diverse group of entities, both clinically and molecularly. Here, we review the evolution of classification schemes in B-cell lymphoma, noting the now standard WHO classification system that is based on immune cell-of-origin and molecular phenotypes. We review how lymphomas arise throughout the B-cell development process as well as the molecular and clinical features of prominent B-cell lymphomas. We provide an overview of the major progress that has occurred over the past decade in terms of our molecular understanding of these diseases. We discuss treatment options available and focus on...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2021 Category: Research Authors: Shingleton, J., Wang, J., Baloh, C., Dave, T., Davis, N., Happ, L., Jadi, O., Kositsky, R., Li, X., Love, C., Panea, R., Qin, Q., Reddy, A., Singhi, N., Smith, E., Thakkar, D., Dave, S. S. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights PERSPECTIVES Source Type: research

[TECHNIQUES] Polygenic Mendelian Randomization
This article reviews the concepts and assumptions underlying the commonly used polygenic MR methods. Using a polygenic score as an instrument is equivalent to a weighted mean of individual SNP results, and the other fundamental averages, median and mode, may also be used to estimate causal effects. Outlier detection is useful for identifying pleiotropic SNPs to be excluded from analysis. Bayesian approaches are available to incorporate prior beliefs about pleiotropy. These methods each entail different assumptions, and together provide a set of sensitivity analyses to help triangulate evidence about causality. (Source: Col...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2021 Category: Research Authors: Dudbridge, F. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development TECHNIQUES Source Type: research

[PERSPECTIVES] Opioid-Induced Molecular and Cellular Plasticity of Ventral Tegmental Area Dopamine Neurons
Opioid drugs are highly valued as potent analgesics; however, there are significant risks associated with long-term use because of their abuse liability. Opioids cause changes in ventral tegmental area (VTA) gene expression and cell activity that have been linked to addiction-related behaviors in rodent models. Here, we focus on VTA dopamine (DA) neurons and review the cellular, structural, and synaptic plasticity changes induced by acute and chronic opioid exposure. We also discuss many avenues for future research including determination of whether opioid neuroadaptations are specific for subpopulations of VTA DA neurons....
Source: Cold Spring Harbor perspectives in medicine - February 1, 2021 Category: Research Authors: Doyle, M. A., Mazei-Robison, M. S. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] The Role of the Central Amygdala in Alcohol Dependence
Alcohol dependence is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking, loss of control in limiting intake, and the emergence of a withdrawal syndrome in the absence of the drug. Accumulating evidence suggests an important role for synaptic transmission in the central nucleus of the amygdala (CeA) in mediating alcohol-related behaviors and neuroadaptive mechanisms associated with alcohol dependence. Acute alcohol facilitates -aminobutyric acid (GABA)ergic transmission in the CeA via both pre- and postsynaptic mechanisms, and chronic alcohol increases baseline GABAergic transmission....
Source: Cold Spring Harbor perspectives in medicine - February 1, 2021 Category: Research Authors: Roberto, M., Kirson, D., Khom, S. Tags: Addiction PERSPECTIVES Source Type: research

[TECHNIQUES] Multivariable Mendelian Randomization and Mediation
Mendelian randomization (MR) is the use of genetic variants associated with an exposure to estimate the causal effect of that exposure on an outcome. Mediation analysis is the method of decomposing the effects of an exposure on an outcome, which act directly, and those that act via mediating variables. These effects are decomposed through the use of multivariable analysis to estimate the causal effects between three types of variables: exposures, mediators, and an outcome. Multivariable MR (MVMR) is a recent extension to MR that uses genetic variants associated with multiple, potentially related exposures to estimate the e...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2021 Category: Research Authors: Sanderson, E. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development TECHNIQUES Source Type: research

[PERSPECTIVES] Pathobiological Origins and Evolutionary History of Highly Pathogenic Avian Influenza Viruses
High-pathogenicity avian influenza (HPAI) viruses have arisen from low-pathogenicity avian influenza (LPAI) viruses via changes in the hemagglutinin proteolytic cleavage site, which include mutation of multiple nonbasic to basic amino acids, duplication of basic amino acids, or recombination with insertion of cellular or viral amino acids. Between 1959 and 2019, a total of 42 natural, independent H5 (n = 15) and H7 (n = 27) LPAI to HPAI virus conversion events have occurred in Europe (n = 16), North America (n = 9), Oceania (n = 7), Asia (n = 5), Africa (n = 4), and South America (n = 1). Thirty-eight of these HPAI outbrea...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2021 Category: Research Authors: Lee, D.-H., Criado, M. F., Swayne, D. E. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research