Cold Spring Harbor perspectives in medicine 
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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] Wnt/frizzled Signaling in Endothelium: A Major Player in Blood-Retinal- and Blood-Brain-Barrier Integrity
The Wnt/frizzled signaling pathway is one of the major regulators of endothelial biology, controlling key cellular activities. Many secreted Wnt ligands have been identified and can initiate diverse signaling via binding to a complex set of Frizzled (Fzd) transmembrane receptors and coreceptors. Roughly, Wnt signaling is subdivided into two pathways: the canonical Wnt/β-catenin signaling pathway whose main downstream effector is the transcriptional coactivator β-catenin, and the noncanonical Wnt signaling pathway, which is subdivided into the Wnt/Ca2+ pathway and the planar cell polarity pathway. Here, we will fo...
Source: Cold Spring Harbor perspectives in medicine - May 17, 2022 Category: Research Authors: Bats, M.-L., Peghaire, C., Delobel, V., Dufourcq, P., Couffinhal, T., Duplaa, C. Tags: Angiogenesis PERSPECTIVES Source Type: research
[RETROSPECTIVE] A History of Cancer Research: Retroviral Oncogenes
The discovery and characterization of retroviral oncogenes were important milestones in cancer research. The viruses turned out not to be key causes of cancer in humans, but the oncogenes they carried provided key clues to the role cellular genes, the proto-oncogene counterparts of these sequences, played in tumorigenesis. In this excerpt from his forthcoming book, Joe Lipsick looks back at early work on retroviruses, such as the experiments that distinguished their ability to infect and transform cells, the groundbreaking work on Src, and some of the controversy surrounding the Nobel Prize awarded for these discoveries. (...
Source: Cold Spring Harbor perspectives in medicine - May 17, 2022 Category: Research Authors: Lipsick, J. Tags: A History of Cancer Research RETROSPECTIVE Source Type: research
[PERSPECTIVES] Causal Inference with Genetic Data: Past, Present, and Future
We present introductory concepts useful to readers unfamiliar with genetically informed methods for causal inference. We conclude that existing applications and foreseeable developments should ensure that we rapidly reap the rewards of this relatively new field, not only in terms of our understanding of human disease and development, but also in terms of tangible translational applications. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - March 1, 2022 Category: Research Authors: Pingault, J.-B., Richmond, R., Davey Smith, G. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development PERSPECTIVES Source Type: research
[TECHNIQUES] Developments from Bulk Optogenetics to Single-Cell Strategies to Dissect the Neural Circuits that Underlie Aberrant Motivational States
Motivational states are regulated by complex networks across brain regions that are composed of genetically and functionally distinct neuronal populations. Disruption within these neural circuits leads to aberrant motivational states and are thought to be the root cause of psychiatric disorders related to reward processing and addiction. Critical technological advances in the field have revolutionized the study of neural systems by allowing the use of optical strategies to precisely control and visualize neural activity within genetically identified neural populations in the brain. This review will provide a brief introduc...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2022 Category: Research Authors: Rodriguez-Romaguera, J., Namboodiri, V. M. K., Basiri, M. L., Stamatakis, A. M., Stuber, G. D. Tags: Addiction TECHNIQUES Source Type: research
[PERSPECTIVES] Molecular Pathology of Lung Cancer
This overview of the molecular pathology of lung cancer includes a review of the most salient molecular alterations of the genome, transcriptome, and the epigenome. The insights provided by the growing use of next-generation sequencing (NGS) in lung cancer will be discussed, and interrelated concepts such as intertumor heterogeneity, intratumor heterogeneity, tumor mutational burden, and the advent of liquid biopsy will be explored. Moreover, this work describes how the evolving field of molecular pathology refines the understanding of different histologic phenotypes of non-small-cell lung cancer (NSCLC) and the underlying...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2022 Category: Research Authors: J. Saller, J., Boyle, T. A. Tags: Lung Cancer: Disease Biology and Its Potential for Clinical Translation PERSPECTIVES Source Type: research
[PERSPECTIVES] Human Genomics and Drug Development
Insights into the genetic basis of human disease are helping to address some of the key challenges in new drug development including the very high rates of failure. Here we review the recent history of an emerging, genomics-assisted approach to pharmaceutical research and development, and its relationship to Mendelian randomization (MR), a well-established analytical approach to causal inference. We demonstrate how human genomic data linked to pharmaceutically relevant phenotypes can be used for (1) drug target identification (mapping relevant drug targets to diseases), (2) drug target validation (inferring the likely effe...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2022 Category: Research Authors: Schmidt, A. F., Hingorani, A. D., Finan, C. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development PERSPECTIVES Source Type: research
[PERSPECTIVES] Emerging HxNy Influenza A Viruses
The continuous emergence and reemergence of diverse subtypes of influenza A viruses, which are known as "HxNy" and are mediated through the reassortment of viral genomes, account for seasonal epidemics, occasional pandemics, and zoonotic outbreaks. We summarize and discuss the characteristics of historic human pandemic HxNy viruses and diverse subtypes of HxNy among wild birds, mammals, and live poultry markets. In addition, we summarize the key molecular features of emerging infectious HxNy influenza viruses from the perspectives of the receptor binding of Hx, the inhibitor-binding specificities and drug-resistance featur...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2022 Category: Research Authors: Liu, W. J., Wu, Y., Bi, Y., Shi, W., Wang, D., Shi, Y., Gao, G. F. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research
[TECHNIQUE] Lung Cancer Computational Biology and Resources
Comprehensive clinical, pathological, and molecular data, when appropriately integrated with advanced computational approaches, are transforming the way we characterize and study lung cancer. Clinically, cancer registry and publicly available historical clinical trial data enable retrospective analyses to examine how socioeconomic factors, patient demographics, and cancer characteristics affect treatment and outcome. Pathologically, digital pathology and artificial intelligence are revolutionizing histopathological image analyses, not only with improved efficiency and accuracy, but also by extracting additional information...
Source: Cold Spring Harbor perspectives in medicine - February 1, 2022 Category: Research Authors: Cai, L., Xiao, G., Gerber, D., D. Minna, J., Xie, Y. Tags: Lung Cancer: Disease Biology and Its Potential for Clinical Translation TECHNIQUE Source Type: research
[TECHNIQUE] Mendelian Randomization: Concepts and Scope
We describe the scope of MR, highlighting the range of applications being made possible as genetic data sets and resources become larger and more freely available. We outline the MR approach in detail, covering concepts, assumptions, and estimation methods. We cover some common misconceptions, provide strategies for overcoming violation of assumptions, and discuss future prospects for extending the clinical applicability, methodological innovations, robustness, and generalizability of MR findings. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - January 4, 2022 Category: Research Authors: Richmond, R. C., Davey Smith, G. Tags: Combining Human Genetics and Causal Inference to Understand Human Disease and Development TECHNIQUE Source Type: research
[PERSPECTIVES] Antivirals Targeting the Neuraminidase
The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and laninamivir) to treat influenza A and B infections. NA changes, naturally occurring or acquired under selective pressure, have been shown to reduce drug binding, thereby affecting the effectiveness of NA inhibitors. Drug resist...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2022 Category: Research Authors: Gubareva, L., Mohan, T. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research
[PERSPECTIVES] Equine Influenza
Horses are the third major mammalian species, along with humans and swine, long known to be subject to acute upper respiratory disease from influenza A virus infection. The viruses responsible are subtype H7N7, which is believed extinct, and H3N8, which circulates worldwide. The equine influenza lineages are clearly divergent from avian influenza lineages of the same subtypes. Their genetic evolution and potential for interspecies transmission, as well as clinical features and epidemiology, are discussed. Equine influenza is spread internationally and vaccination is central to control efforts. The current mechanism of inte...
Source: Cold Spring Harbor perspectives in medicine - January 4, 2022 Category: Research Authors: Chambers, T. M. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research
[PERSPECTIVES] Accessory Gene Products of Influenza A Virus
Influenza A virus has long been known to encode 10 major polypeptides, produced, almost without exception, by every natural isolate of the virus. These polypeptides are expressed in readily detectable amounts during infection and are either fully essential or their loss severely attenuates virus replication. More recent work has shown that this core proteome is elaborated by expression of a suite of accessory gene products that tend to be expressed at lower levels through noncanonical transcriptional and/or translational events. Expression and activity of these accessory proteins varies between virus strains and is nonesse...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2021 Category: Research Authors: Pinto, R. M., Lycett, S., Gaunt, E., Digard, P. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research
[PERSPECTIVES] Human Influenza Epidemiology
Influenza virus infections are common in people of all ages. Epidemics occur in the winter months in temperate locations and at varying times of the year in subtropical and tropical locations. Most influenza virus infections cause mild and self-limiting disease, and around one-half of all infections occur with a fever. Only a small minority of infections lead to serious disease requiring hospitalization. During epidemics, the rates of influenza virus infections are typically highest in school-age children. The clinical severity of infections tends to increase at the extremes of age and with the presence of underlying medic...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2021 Category: Research Authors: Ryu, S., Cowling, B. J. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research
[TECHNIQUE] Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy Development
Experimental preclinical models have been a cornerstone of lung cancer translational research. Work in these model systems has provided insights into the biology of lung cancer subtypes and their origins, contributed to our understanding of the mechanisms that underlie tumor progression, and revealed new therapeutic vulnerabilities. Initially patient-derived lung cancer cell lines were the main preclinical models available. The landscape is very different now with numerous preclinical models for research each with unique characteristics. These include genetically engineered mouse models (GEMMs), patient-derived xenografts ...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2021 Category: Research Authors: Arnal-Estape, A., Foggetti, G., Starrett, J. H., Nguyen, D. X., Politi, K. Tags: Lung Cancer: Disease Biology and Its Potential for Clinical Translation TECHNIQUE Source Type: research
[PERSPECTIVES] Influenza Immunization in the Context of Preexisting Immunity
Although we develop influenza immunity from an early age, it is insufficient to prevent future infection with antigenically novel strains. One proposed way to generate long-term protective immunity against a broad range of influenza virus strains is to boost responses to the conserved epitopes on the hemagglutinin, the major surface glycoprotein on the influenza virus. Influenza-specific humoral immunity comprises a large fraction of the overall immune memory in humans, and it has been long recognized that preexisting immunity to influenza shapes the response to subsequent influenza infections and vaccinations. However, th...
Source: Cold Spring Harbor perspectives in medicine - November 1, 2021 Category: Research Authors: Linderman, S. L., Ellebedy, A. H., Davis, C., Eberhardt, C. S., Antia, R., Ahmed, R., Zarnitsyna, V. I. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research
