[PERSPECTIVES] Growth Factors and Alcohol Use Disorder
Neurotrophic growth factors were originally characterized for their support in neuronal differentiation, outgrowth, and survival during development. However, it has been acknowledged that they also play a vital role in the adult brain. Abnormalities in growth factors have been implicated in a variety of neurological and psychiatric disorders, including alcohol use disorder (AUD). This work focuses on the interaction between alcohol and growth factors. We review literature suggesting that several growth factors play a unique role in the regulation of alcohol consumption, and that breakdown in these growth factor systems is ...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Liran, M., Rahamim, N., Ron, D., Barak, S. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Psychostimulant-Induced Adaptations in Nucleus Accumbens Glutamatergic Transmission
Carrying different aspects of emotional and motivational signals, glutamatergic synaptic projections from multiple limbic and paralimbic brain regions converge to the nucleus accumbens (NAc), in which these arousing signals are processed and prioritized for behavioral output. In animal models of drug addiction, some key drug-induced alterations at NAc glutamatergic synapses underlie important cellular and circuit mechanisms that promote subsequent drug taking, seeking, and relapse. With the focus of cocaine, we review changes at NAc glutamatergic synapses that occur after different drug procedures and abstinence durations,...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Wright, W. J., Dong, Y. Tags: Addiction PERSPECTIVES Source Type: research

[PERSPECTIVES] Influenza in High-Risk Hosts--Lessons Learned from Animal Models
Factoring significantly into the global burden of influenza disease are high-risk populations that suffer the bulk of infections. Classically, the very young, very old, and pregnant women have been identified as high-risk populations; however, recent research has uncovered several other conditions that contribute to severe infection. By using varied animal models, researchers have identified molecular mechanisms underpinning the increased likelihood for infection due to obesity and malnourishment, as well as insight into the role sex hormones play in antiviral immunity in males, in females, and across the life span. Additi...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Honce, R., Wohlgemuth, N., Meliopoulos, V. A., Short, K. R., Schultz-Cherry, S. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[TECHNIQUE] Experimental Approaches to Identify Host Factors Important for Influenza Virus
An ever-expanding toolkit of experimental methods provides the means to discover and characterize host factors important for influenza virus. Here, we describe common methods for investigating genetic relationships and physical interactions between virus and host. A comprehensive knowledge of host:virus interactions is key to understanding how influenza virus exploits the host cell and to potentially identify vulnerabilities that may be manipulated to prevent or treat disease. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Schaack, G. A., Mehle, A. Tags: Influenza: The Cutting Edge TECHNIQUE Source Type: research

[PERSPECTIVES] Genetic Risk Assessment in Psychiatry
Most psychiatric disorders of pediatric and adult onset are caused by a complex interplay of genetic and environmental risk factors. Risk assessment in genetic counseling is correspondingly complicated. Outside of neurodevelopmental conditions, genetic and genomic testing has not achieved clinical utility. Genetic counselors most often base risk assessment on the client's medical and family history and empiric recurrence risk data. In rare cases significant familial risk may arise from variants of large effect. New approaches such as polygenic risk scores have the potential to inform diagnosis and management of affected in...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Peay, H. L. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Impact of Emerging Technologies in Prenatal Genetic Counseling
For decades, prenatal testing has been offered to evaluate pregnancies for genetic conditions. In recent years, the number of testing options and range of testing capabilities has dramatically increased. Because of the risks associated with invasive diagnostic testing, research has focused on the detection of genetic conditions through screening technologies such as cell-free DNA. Screening for aneuploidy, copy number variants, and monogenic disorders is clinically available using a sample of maternal blood, but limited data exist on the accuracy of some of these testing options. Additional research is needed to examine th...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Stevens, B. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Normal Hematopoiesis Is a Balancing Act of Self-Renewal and Regeneration
The hematopoietic system is highly organized to maintain its functional integrity and to meet lifelong organismal demands. Hematopoietic stem cells (HSCs) must balance self-renewal with differentiation and the regeneration of the blood system. It is a complex balancing act between these competing HSC functions. Although highly quiescent at steady state, HSCs become activated in response to inflammatory cytokines and regenerative challenges. This activation phase leads to many intrinsic stresses such as replicative, metabolic, and oxidative stress, which can cause functional decline, impaired self-renewal, and exhaustion of...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Olson, O. C., Kang, Y.-A., Passegue, E. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights PERSPECTIVES Source Type: research

[PERSPECTIVES] Epigenetic Mechanisms in Leukemias and Lymphomas
Although we are just beginning to understand the mechanisms that regulate the epigenome, aberrant epigenetic programming has already emerged as a hallmark of hematologic malignancies including acute myeloid leukemia (AML) and B-cell lymphomas. Although these diseases arise from the hematopoietic system, the epigenetic mechanisms that drive these malignancies are quite different. Yet, in all of these tumors, somatic mutations in transcription factors and epigenetic modifiers are the most commonly mutated set of genes and result in multilayered disruption of the epigenome. Myeloid and lymphoid neoplasms generally manifest ep...
Source: Cold Spring Harbor perspectives in medicine - December 1, 2020 Category: Research Authors: Duy, C., Beguelin, W., Melnick, A. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights PERSPECTIVES Source Type: research

[PERSPECTIVES] The Evolution and Ecology of Resistance in Cancer Therapy
Despite the continuous deployment of new treatment strategies and agents over many decades, most disseminated cancers remain fatal. Cancer cells, through their access to the vast information of the human genome, have a remarkable capacity to deploy adaptive strategies for even the most effective treatments. We note there are two critical steps in the clinical manifestation of treatment resistance. The first, which is widely investigated, requires molecular machinery necessary to eliminate the cytotoxic effect of the treatment. However, the emergence of a resistant phenotype is not in itself clinically significant. That is,...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: Gatenby, R. A., Brown, J. S. Tags: Cancer Evolution PERSPECTIVES Source Type: research

[RETRACTION] Retraction: The Evolution and Ecology of Resistance in Cancer Therapy
(Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: Gatenby, R., Brown, J. Tags: RETRACTION Source Type: research

[TECHNIQUES] Synthetic Virology: Building Viruses to Better Understand Them
Generally comprised of less than a dozen components, RNA viruses can be viewed as well-designed genetic circuits optimized to replicate and spread within a given host. Understanding the molecular design that enables this activity not only allows one to disrupt these circuits to study their biology, but it provides a reprogramming framework to achieve novel outputs. Recent advances have enabled a "learning by building" approach to better understand virus biology and create valuable tools. Below is a summary of how modifying the preexisting genetic framework of influenza A virus has been used to track viral movemen...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: tenOever, B. R. Tags: Influenza: The Cutting Edge TECHNIQUES Source Type: research

[PERSPECTIVES] The Structure, Function, and Pathobiology of the Influenza A and B Virus Ion Channels
Influenza A virus AM2 protein is an integral membrane protein that is an ion channel (also known as a viroporin). The channel has 24 extracellular residues, 19 residues that span the membrane once and acts as both the channel pore and also the membrane anchoring domain, and a 54-residue cytoplasmic tail. The M2 protein has four identical chains linked via two disulfide bonds that form a four-helix bundle that is 107–108 more permeable to protons than Na+ ions. The M2 channel is activated by low pH, His residue 37 is the pH sensor, and Trp residue 41 is the channel gate. The channel is blocked by the antiviral drug am...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: Lamb, R. A. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[TECHNIQUES] Cellular Plasticity during Metastasis: New Insights Provided by Intravital Microscopy
Metastasis is a highly dynamic process during which cancer and microenvironmental cells undergo a cascade of events required for efficient dissemination throughout the body. During the metastatic cascade, tumor cells can change their state and behavior, a phenomenon commonly defined as cellular plasticity. To monitor cellular plasticity during metastasis, high-resolution intravital microscopy (IVM) techniques have been developed and allow us to visualize individual cells by repeated imaging in animal models. In this review, we summarize the latest technological advancements in the field of IVM and how they have been applie...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: Margarido, A. S., Bornes, L., Vennin, C., van Rheenen, J. Tags: Metastasis: Mechanism to Therapy TECHNIQUES Source Type: research

[PERSPECTIVES] Premetastasis
Sterile inflammation within primary tumor tissues can spread to distant organs that are devoid of tumor cells. This happens in a manner dependent on tumor-led secretome, before the actual metastasis occurs. The premetastatic microenvironment is established in this way and is at least partly regulated by hijacking the host innate immune system. The biological manifestation of premetastasis include increased vascular permeability, cell mobilization via the blood stream, degradation of the extracellular matrix, immunosuppression, and host antineoplastic activities. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: Maru, Y. Tags: Metastasis: Mechanism to Therapy PERSPECTIVES Source Type: research

[PERSPECTIVES] Interferon-Free Hepatitis C Virus Therapy
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with ~71 million chronically infected individuals worldwide. Treatment of patients with HCV-related liver disease has advanced considerably thanks to the development of new direct-acting antiviral drugs that are now administered as highly potent, safe, and well-tolerated combinations with a high barrier to resistance. International organizations, such as the European Association for the Study of the Liver, the American Association for the Study of Liver Diseases jointly with the Infectious Diseases Society of America, or the World Health Organizat...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: Pawlotsky, J.-M. Tags: Hepatitis C Virus: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[PERSPECTIVES] Birds of a Feather? Genetic Counseling, Genetic Testing, and Humanism
Humanism is a philosophy that emphasizes rational, scientific, and empiric analysis of the world we live in to improve the physical, social, and psychological life of humanity. Although individual genetic counselors may or may not identify as humanists, genetic counseling and genetic testing are primarily humanistic endeavors because they are situated in the context of humanistic medicine in the westernized world. Humanistic goals are also implicit and explicit in the profession and practice of genetic counselors. This review examines the relationship between humanism and genetic counseling, highlighting situations in whic...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: Resta, R. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Genetic Counseling and Assisted Reproductive Technologies
Despite the ever-increasing number of patients undergoing fertility treatments and the expanded use of genetic testing in this context, there has been limited focus in the literature on the involvement of genetics professionals in the assisted reproductive technology (ART) setting. Here we discuss the importance of genetic counseling within reproductive medicine. We review how genetic testing of embryos is performed, the process of gamete donation, the challenges associated with genetic testing, and the complexities of genetic test result interpretation. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: Lilienthal, D., Cahr, M. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Impact of Genetics on Mature Lymphoid Leukemias and Lymphomas
Recurrent genetic aberrations have long been recognized in mature lymphoid leukemias and lymphomas. As conventional karyotypic and molecular cloning techniques evolved in the 1970s and 1980s, multiple cytogenetic aberrations were identified in lymphomas, often balanced translocations that juxtaposed oncogenes to the immunoglobulin (IG) or T-cell receptor (TR) loci, leading to dysregulation. However, genetic characterization and classification of lymphoma by conventional cytogenetic methods is limited by the infrequent occurrence of recurrent karyotypic abnormalities in many lymphoma subtypes and by the frequent difficulty ...
Source: Cold Spring Harbor perspectives in medicine - November 2, 2020 Category: Research Authors: Bailey, N. G., Elenitoba-Johnson, K. S. J. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights PERSPECTIVES Source Type: research

[RETROSPECTIVE] The 1918 Influenza Pandemic and Its Legacy
Just over a century ago in 1918–1919, the "Spanish" influenza pandemic appeared nearly simultaneously around the world and caused extraordinary mortality—estimated at 50–100 million fatalities—associated with unexpected clinical and epidemiological features. The pandemic's sudden appearance and high fatality rate were unprecedented, and 100 years later still serve as a stark reminder of the continual threat influenza poses. Sequencing and reconstruction of the 1918 virus have allowed scientists to answer many questions about its origin and pathogenicity, although many questions remain. Sev...
Source: Cold Spring Harbor perspectives in medicine - September 30, 2020 Category: Research Authors: Taubenberger, J. K., Morens, D. M. Tags: Influenza: The Cutting Edge RETROSPECTIVE Source Type: research

[PERSPECTIVES] Influenza Vaccines Delivered in Early Childhood Could Turn Antigenic Sin into Antigenic Blessings
Substantial evidence has accumulated that "original antigenic sin" is a central factor shaping immune responses against influenza viruses. Here, we argue that this propensity of initial influenza virus exposure to establish a lifelong immunological imprint presents a remarkable opportunity: Immunization of infants prior to their initial, natural viral exposure could circumvent narrow immunological imprinting directed toward a single viral strain. Simultaneous initial exposure to antigens from multiple influenza strains via vaccination holds the promise of extending immunological imprinting across all currently ci...
Source: Cold Spring Harbor perspectives in medicine - September 30, 2020 Category: Research Authors: Worobey, M., Plotkin, S., Hensley, S. E. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] The Etiology and Impact of Muscle Wasting in Metastatic Cancer
Metastasis arises when cancer cells disseminate from their site of origin and invade distant organs. While cancer cells rarely colonize muscle, they often induce a debilitating muscle-wasting condition known as cachexia that compromises feeding, breathing, and cardiac function in metastatic cancer patients. In fact, nearly 80% of metastatic cancer patients experience a spectrum of muscle-wasting states, which deteriorates the quality of life and overall survival of cancer patients. Muscle wasting in cancer results from increased muscle catabolism induced by circulating tumor factors and a systemic metabolic dysfunction. In...
Source: Cold Spring Harbor perspectives in medicine - September 30, 2020 Category: Research Authors: Biswas, A. K., Acharyya, S. Tags: Metastasis: Mechanism to Therapy PERSPECTIVES Source Type: research

[PERSPECTIVES] Bone Tropism in Cancer Metastases
Bone is a frequent site of metastases in many cancers. Both bone properties and the tumor-intrinsic traits are associated with the metastatic propensity to bone (i.e., the bone tropism). Whereas an increasing body of mechanistic studies expanded our understanding on bone tropism, they also revealed complexity across the bone lesions originated from different cancer types. In this review, we will discuss the physical, chemical, and biological properties of bone microenvironment, identify potential players in every stage of bone metastases, and introduce some of the known mechanisms regulating the bone colonization. Our obje...
Source: Cold Spring Harbor perspectives in medicine - September 30, 2020 Category: Research Authors: Wang, H., Zhang, W., Bado, I., Zhang, X. H.- F. Tags: Metastasis: Mechanism to Therapy PERSPECTIVES Source Type: research

[PERSPECTIVES] Bridging the Gap between Scientific Advancement and Real-World Application: Pediatric Genetic Counseling for Common Syndromes and Single-Gene Disorders
Screening and diagnostic testing for single-gene disorders and common syndromes in the pediatric setting frequently generate data that are challenging to interpret, and the ability to diagnose genetic conditions has outpaced the development of successful treatments or cures. Genetic testing is now integrated purposefully into a variety of primary and specialty care clinics, creating an increased requirement for genetic literacy among providers and patients, as well as a growing need to incorporate genetic counseling services into mainstream clinical practice. The practice of pediatric genetic counseling encompasses a uniqu...
Source: Cold Spring Harbor perspectives in medicine - September 30, 2020 Category: Research Authors: McGlynn, J. A., Langfelder-Schwind, E. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Evolving Roles of Genetic Counselors in the Clinical Laboratory
Genetic counselors (GCs) possess several core competencies that provide direct benefit in the clinical laboratory setting. Communication with clients about complex information such as test methodology or results and the skills of facilitation and translation of complex information were recognized as important skills early in the establishment of GCs in laboratories. The clinical expertise of GCs serves as the background and experience from which they facilitate complex laboratory cases. Early roles for GCs in the laboratory also included result reporting, case management, and test development. The scope of roles has broade...
Source: Cold Spring Harbor perspectives in medicine - September 30, 2020 Category: Research Authors: Cho, M. T., Guy, C. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] PTEN in Regulating Hematopoiesis and Leukemogenesis
PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. By counteracting the PI3K/AKT/mTOR pathway, PTEN plays an essential role in regulating hematopoietic stem cells (HSCs) self-renewal, migration, lineage commitment, and differentiation. PTEN also plays important roles in suppressing leukemogenesis, especially T-cell acute lymphoblastic leukemia (T-ALL). Herein, we will review the function of PTEN in regulating hematopoiesis and leukemogenesis and discuss potential therapeutic approaches against leukemia with PTEN mutations. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - September 30, 2020 Category: Research Authors: Wu, Y., Zhu, H., Wu, H. Tags: The PTEN Family PERSPECTIVES Source Type: research

[PERSPECTIVES] PTEN: Bridging Endocytosis and Signaling
The transduction of signals in the PTEN/PI3-kinase (PI3K) pathway is built around a phosphoinositide (PIP) lipid messenger, phosphatidylinositol trisphosphate, PI(3,4,5)P3 or PIP3. Another, more ancient role of this family of messengers is the control of endocytosis, where a handful of separate PIPs act like postal codes. Prominent among them is PI(3)P, which helps to ensure that endocytic vesicles, their cargo, and membranes themselves reach their correct destinations. Traditionally, the cancer and the endocytic functions of the PI3K signaling pathway have been studied by cancer and membrane biologists, respectively, with...
Source: Cold Spring Harbor perspectives in medicine - September 30, 2020 Category: Research Authors: Lee, M. F., Trotman, L. C. Tags: The PTEN Family PERSPECTIVES Source Type: research

[PERSPECTIVES] Structure and Function of the Influenza Virus Transcription and Replication Machinery
Transcription and replication of the influenza virus RNA genome is catalyzed by the viral heterotrimeric RNA-dependent RNA polymerase in the context of viral ribonucleoprotein (vRNP) complexes. Atomic resolution structures of the viral RNA synthesis machinery have offered insights into the initiation mechanisms of viral transcription and genome replication, and the interaction of the viral RNA polymerase with host RNA polymerase II, which is required for the initiation of viral transcription. Replication of the viral RNA genome by the viral RNA polymerase depends on host ANP32A, and host-specific sequence differences in AN...
Source: Cold Spring Harbor perspectives in medicine - August 31, 2020 Category: Research Authors: Fodor, E., te Velthuis, A. J. W. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Normal Aging and Its Role in Cancer Metastasis
Metastasis is the most common cause of death, with treatments failing to provide a durable response. Aging is a key prognostic factor in many cancers. Emerging data suggest that normal age-related changes in the tumor microenvironment can contribute to metastatic progression. These changes encompass secreted factors, biophysical changes, and changes in both stromal and immune cell populations. These data also highlight the importance of conducting studies in preclinical models of appropriate age. Ultimately, therapies may also need to be tailored to reflect patient age, as markers of metastatic disease differ in young and ...
Source: Cold Spring Harbor perspectives in medicine - August 31, 2020 Category: Research Authors: Fane, M., Weeraratna, A. T. Tags: Metastasis: Mechanism to Therapy PERSPECTIVES Source Type: research

[PERSPECTIVES] Control of HCV Infection by Natural Killer Cells and Macrophages
Host defense against invading pathogens within the liver is dominated by innate immunity. Natural killer (NK) cells have been implicated at all stages of hepatitis C virus (HCV) infection, from providing innate protection to contributing to treatment-induced clearance. Decreased NK cell levels, altered NK cell subset distribution, activation marker expression, and functional polarization toward a cytolytic phenotype are hallmarks of chronic HCV infection. Interferon α (IFN-α) is a potent activator of NK cells; therefore, it is not surprising that NK cell activation has been identified as a key factor associated...
Source: Cold Spring Harbor perspectives in medicine - August 31, 2020 Category: Research Authors: Rosen, H. R., Golden-Mason, L. Tags: Hepatitis C Virus: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[PERSPECTIVES] Impact of Immunometabolism on Cancer Metastasis: A Focus on T Cells and Macrophages
Despite improved treatment options, cancer remains the leading cause of morbidity and mortality worldwide, with 90% of this mortality correlated to the development of metastasis. Since metastasis has such an impact on treatment success, disease outcome, and global health, it is important to understand the different steps and factors playing key roles in this process, how these factors relate to immune cell function and how we can target metabolic processes at different steps of metastasis in order to improve cancer treatment and patient prognosis. Recent insights in immunometabolism direct to promising therapeutic targets ...
Source: Cold Spring Harbor perspectives in medicine - August 31, 2020 Category: Research Authors: Flerin, N. C., Pinioti, S., Menga, A., Castegna, A., Mazzone, M. Tags: Metastasis: Mechanism to Therapy PERSPECTIVES Source Type: research

[TECHNIQUE] Connecting Genotype with Behavioral Phenotype in Mouse Models of Autism Associated with PTEN Mutations
A subset of individuals with autism spectrum disorder (ASD) and macrocephaly carry mutations in the gene PTEN. Animal models, particularly mice, have been helpful in establishing a causal role for Pten mutations in autism-relevant behavioral deficits. These models are a useful tool for investigating neurobiological mechanisms of these behavioral phenotypes and developing potential therapeutic interventions. Here we provide an overview of various genetic mouse models that have been used to characterize behavioral phenotypes caused by perturbation of Pten. We discuss convergent and divergent phenotypes across models with the...
Source: Cold Spring Harbor perspectives in medicine - August 31, 2020 Category: Research Authors: Clipperton-Allen, A. E., Page, D. T. Tags: The PTEN Family TECHNIQUE Source Type: research

[PERSPECTIVES] Genetic Counseling, Personalized Medicine, and Precision Health
Millions of individuals in the United States will have their exomes and genomes sequenced over the next 5 years as the use of genomic sequencing technologies in clinical care grows and as initiatives in personalized medicine and precision health move forward. As a result, we will see a shift away from the patient population of early adopters who pursued direct-to-consumer (DTC) testing and paid thousands of dollars to get their genomes sequenced and toward a different and more diverse set of test takers. Early data suggest that these individuals will have different motivations for pursuing genomic sequencing and will be le...
Source: Cold Spring Harbor perspectives in medicine - August 31, 2020 Category: Research Authors: Ramos, E. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Psychological Issues in Managing Families with Inherited Cardiovascular Diseases
The field of cardiovascular genetic counseling has evolved dramatically in recent years largely to manage the unique psychological needs of the inherited cardiovascular disease patient population. For many, there can be difficulty in coming to terms with a diagnosis, whether it be adjusting to lifestyle recommendations such as exclusion from competitive sports or living with a small but remarkable risk of sudden cardiac death. For those considered at risk of life-threatening ventricular arrhythmias, the decision to have an implantable cardioverter defibrillator can be difficult. Living with the device, especially for those...
Source: Cold Spring Harbor perspectives in medicine - August 31, 2020 Category: Research Authors: Ingles, J. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] PTEN as a Guardian of the Genome: Pathways and Targets
Faithful transmission of genetic information is only possible with the structural and functional integrity of the genome. PTEN has been recognized as a guardian of the genome since the identification of its noncanonical localization and function in the nucleus. Yet, the role of PTEN in guarding the genome relies on integration of diverse mechanisms elicited by its canonical activity in antagonizing PI3K as well as emerging noncanonical functions. In the nucleus, PTEN maintains the structural integrity of chromosomes and the architecture of heterochromatin by physically interacting with chromosomal and nucleosomal component...
Source: Cold Spring Harbor perspectives in medicine - August 31, 2020 Category: Research Authors: Fan, X., Kraynak, J., Knisely, J. P. S., Formenti, S. C., Shen, W. H. Tags: The PTEN Family PERSPECTIVES Source Type: research

[CORRIGENDUM] Corrigendum: Mechanism of Bone Mineralization
(Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - August 2, 2020 Category: Research Authors: Murshed, M. Tags: CORRIGENDUM Source Type: research

[PERSPECTIVES] Influenza Hemagglutinin Structures and Antibody Recognition
Hemagglutinin (HA) is most abundant glycoprotein on the influenza virus surface. Influenza HA promotes viral entry by engaging the receptor and mediating virus–host membrane fusion. At the same time, HA is the major antigen of the influenza virus. HA antigenic shift can result in pandemics, whereas antigenic drift allows human circulating strains to escape herd immunity. Most antibody responses against HA are strain-specific. However, antibodies that have neutralizing activities against multiple strains or even subtypes have now been discovered and characterized. These broadly neutralizing antibodies (bnAbs) target c...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2020 Category: Research Authors: Wu, N. C., Wilson, I. A. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Quantifying between-Host Transmission in Influenza Virus Infections
The error-prone replication and life cycle of influenza virus generate a diverse set of genetic variants. Transmission between hosts strictly limits both the number of virus particles and the genetic diversity of virus variants that reach a new host and establish an infection. This sharp reduction in the virus population at transmission––the transmission bottleneck––is significant to the evolution of influenza virus and to its epidemic and pandemic potential. This review describes transmission bottlenecks and their effect on the diversity and evolution of influenza virus. It also reviews the methods...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2020 Category: Research Authors: Johnson, K. E. E., Ghedin, E. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[TECHNIQUE] Zebrafish In Vivo Models of Cancer and Metastasis
Metastasis, the dispersal of cancer cells from a primary tumor to secondary sites within the body, is the leading cause of cancer-related death. Animal models have been an indispensable tool to investigate the complex interactions between the cancer cells and the tumor microenvironment during the metastatic cascade. The zebrafish (Danio rerio) has emerged as a powerful vertebrate model for studying metastatic events in vivo. The zebrafish has many attributes including ex-utero development, which facilitates embryonic manipulation, as well as optically transparent tissues, which enables in vivo imaging of fluorescently labe...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2020 Category: Research Authors: Astell, K. R., Sieger, D. Tags: Metastasis: Mechanism to Therapy TECHNIQUE Source Type: research

[PERSPECTIVES] New Approaches on Cancer Immunotherapy
Metastasis, which occurs when cancer cells disseminate from the primary tumor site to other parts of the body, is the primary cause of mortality in patients, and the recurrence of multiple metastatic tumors is an obstacle to eliminating cancer. Recent clinical studies demonstrated that patients who respond to immunotherapy have longer survival rates with lower metastatic relapse, suggesting that immunotherapy may be one of the solutions to overcome cancer metastasis. Indeed, various host immune cells not only shape the tumor microenvironment but also participate in multiple stages of metastasis. Therefore, to improve clini...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2020 Category: Research Authors: Cha, J.-H., Chan, L.-C., Song, M. S., Hung, M.-C. Tags: Metastasis: Mechanism to Therapy PERSPECTIVES Source Type: research

[PERSPECTIVES] Tumor-Based Genetic Testing and Familial Cancer Risk
As genetic testing on somatic tumor tissue becomes a more routine part of personalized cancer treatment, a growing opportunity arises to identify hereditary germline variants within those results. These germline results can affect future cancer screening for both patients and their family members. Finding this germline information can be complicated as a result of differences between somatic and germline testing processes, nomenclature, and outcome goals (e.g., treatment impact). The goal of this review is to highlight differences between somatic and germline testing and outline a potential guide to allow for appropriate c...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2020 Category: Research Authors: Forman, A., Sotelo, J. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Informed Consent in the Genomics Era
Informed consent, the process of gathering autonomous authorization for a medical intervention or medical research participation, is a fundamental component of medical practice. Medical informed consent assumes decision-making capacity, voluntariness, comprehension, and adequate information. The increasing use of genetic testing, particularly genomic sequencing, in clinical and research settings has presented many new challenges for clinicians and researchers when obtaining informed consent. Many of these challenges revolve around the need for patient comprehension of sufficient information. Genomic sequencing is complex&m...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2020 Category: Research Authors: Rego, S., Grove, M. E., Cho, M. K., Ormond, K. E. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Metabolic Role of PTEN in Insulin Signaling and Resistance
Phosphatase and tensin homolog (PTEN) is most prominently known for its function in tumorigenesis. However, a metabolic role of PTEN is emerging as a result of its altered expression in type 2 diabetes (T2D), which results in impaired insulin signaling and promotion of insulin resistance during the pathogenesis of T2D. PTEN functions in regulating insulin signaling across different organs have been identified. Through the use of a variety of models, such as tissue-specific knockout (KO) mice and in vitro cell cultures, PTEN's role in regulating insulin action has been elucidated across many cell types. Herein, we will revi...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2020 Category: Research Authors: Li, Y. Z., Di Cristofano, A., Woo, M. Tags: The PTEN Family PERSPECTIVES Source Type: research

[RETROSPECTIVE] Discovery of the PTEN Tumor Suppressor and Its Connection to the PI3K and AKT Oncogenes
PTEN (phosphatase and tensin homolog on chromosome 10) was discovered over 20 years ago in 1997 and linked to the phosphatidylinositol 3-kinase (PI3K) and AKT oncogenes the following year. The discovery of PTEN emerged from the linked concepts of oncogenes and tumor suppressor genes that cause and prevent cancer and the fields of tumor viruses and human cancer genetics from which these two concepts arose. While much has been learned since, the initial discovery and characterization, including the discovery that PTEN is a regulator of PI3K and AKT, provide the foundation on which we continue to build our knowledge. To provi...
Source: Cold Spring Harbor perspectives in medicine - August 2, 2020 Category: Research Authors: Parsons, R. Tags: The PTEN Family RETROSPECTIVE Source Type: research

[PERSPECTIVES] The Ecology and Evolution of Influenza Viruses
The patterns and processes of influenza virus evolution are of fundamental importance, underpinning such traits as the propensity to emerge in new host species and the ability to rapidly generate antigenic variation. Herein, we review key aspects of the ecology and evolution of influenza viruses. We begin with an exploration of the origins of influenza viruses within the orthomyxoviruses, showing how our perception of the evolutionary history of these viruses has been transformed with metagenomic sequencing. We then outline the diversity of virus subtypes in different species and the processes by which these viruses have e...
Source: Cold Spring Harbor perspectives in medicine - June 30, 2020 Category: Research Authors: Wille, M., Holmes, E. C. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Ferreting Out Influenza Virus Pathogenicity and Transmissibility: Past and Future Risk Assessments in the Ferret Model
As influenza A viruses continue to jump species barriers, data generated in the ferret model to assess influenza virus pathogenicity, transmissibility, and tropism of these novel strains continues to inform an increasing scope of public health–based applications. This review presents the suitability of ferrets as a small mammalian model for influenza viruses and describes the breadth of pathogenicity and transmissibility profiles possible in this species following inoculation with a diverse range of viruses. Adaptation of aerobiology-based techniques and analyses have furthered our understanding of data obtained from...
Source: Cold Spring Harbor perspectives in medicine - June 30, 2020 Category: Research Authors: Belser, J. A., Pulit-Penaloza, J. A., Maines, T. R. Tags: Influenza: The Cutting Edge PERSPECTIVES Source Type: research

[PERSPECTIVES] Extracellular Vesicles and Metastasis
Secretion of cell contents through extracellular vesicles (EVs), such as exosomes and microvesicles, is a fundamental cell behavior. Compared with their normal counterparts, cancer cells are different in the amount and composition of EVs they secrete as a result of intrinsic and extrinsic (microenvironmental) alterations. Although EVs were originally recognized as a means to remove undesired cell components, recent studies show their critical role in mediating intercellular interaction through cargo transport. In cancer, EVs can be transferred between different cancer cell subpopulations and between cancer and normal cells...
Source: Cold Spring Harbor perspectives in medicine - June 30, 2020 Category: Research Authors: Wang, S. E. Tags: Metastasis: Mechanism to Therapy PERSPECTIVES Source Type: research

[PERSPECTIVES] Cancer Stem Cells and Epithelial-to-Mesenchymal Transition in Cancer Metastasis
The cancer stem cell (CSC) concept stands for undifferentiated tumor cells with the ability to initiate heterogeneous tumors. It is also relevant in metastasis and can explain how metastatic tumors mirror the heterogeneity of primary tumors. Cellular plasticity, including the epithelial-to-mesenchymal transition (EMT), enables the generation of CSCs at different steps of the metastatic process including metastatic colonization. In this review, we update the concept of CSCs and provide evidence of the existence of metastatic stem cells (MetSCs). In addition, we highlight the nuanced understanding of EMT that has been gained...
Source: Cold Spring Harbor perspectives in medicine - June 30, 2020 Category: Research Authors: Celia-Terrassa, T., Jolly, M. K. Tags: Metastasis: Mechanism to Therapy PERSPECTIVES Source Type: research

[PERSPECTIVES] A Person-Centered Approach to Cardiovascular Genetic Testing
Cardiovascular genetic counselors provide guidance to people facing the reality or prospect of inherited cardiovascular conditions. Key activities in this role include discussing clinical cardiac screening for at-risk family members and offering genetic testing. Psychological factors often influence whether patients choose to have genetic testing and how they understand and communicate the results to at-risk relatives, so psychological counseling increases the impact of genetic education and medical recommendations. This work reviews the literature on the factors that influence patient decisions about cardiovascular geneti...
Source: Cold Spring Harbor perspectives in medicine - June 30, 2020 Category: Research Authors: Platt, J. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Predictive Genetic Counseling for Neurodegenerative Diseases: Past, Present, and Future
Predictive genetic counseling for neurodegenerative diseases commenced with Huntington's disease (HD). Because the psychological issues and outcomes have been best studied in HD, the HD genetic counseling and testing protocol is still accepted as the gold standard for genetic counseling for these diseases. Yet, advances in genomic technology have produced an abundance of new information about the genetics of diseases such as Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, and Parkinson's disease. The resulting expansion of genetic tests together with the availability of direct-to-consumer testi...
Source: Cold Spring Harbor perspectives in medicine - June 30, 2020 Category: Research Authors: Goldman, J. S. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Posttranslational Regulation and Conformational Plasticity of PTEN
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor that is frequently down-modulated in human cancer. PTEN inhibits the phosphatidylinositol 3-phosphate kinase (PI3K)/AKT pathway through its lipid phosphatase activity. Multiple PI3K/AKT-independent actions of PTEN, protein-phosphatase activities and functions within the nucleus have also been described. PTEN, therefore, regulates many cellular processes including cell proliferation, survival, genomic integrity, polarity, migration, and invasion. Even a modest decrease in the functional dose of PTEN may promote cancer development. Understan...
Source: Cold Spring Harbor perspectives in medicine - June 30, 2020 Category: Research Authors: Kotelevets, L., Trifault, B., Chastre, E., Scott, M. G. H. Tags: The PTEN Family PERSPECTIVES Source Type: research