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] Hepatitis C Virus Replication
Replication and amplification of the viral genome is a key process for all viruses. For hepatitis C virus (HCV), a positive-strand RNA virus, amplification of the viral genome requires the synthesis of a negative-sense RNA template, which is in turn used for the production of new genomic RNA. This process is governed by numerous proteins, both host and viral, as well as distinct lipids and specific RNA elements within the positive- and negative-strand RNAs. Moreover, this process requires specific changes to host cell ultrastructure to create microenvironments conducive to viral replication. This review will focus on descr...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2020 Category: Research Authors: Tabata, K., Neufeldt, C. J., Bartenschlager, R. Tags: Hepatitis C Viruses: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[PERSPECTIVES] Hepatitis C Virus Epidemiology and the Impact of Interferon-Free Hepatitis C Virus Therapy
The public health impact of hepatitis C virus (HCV) infection has been realized only recently. Globally, 71 million people are living with HCV chronic infection. HCV prevalence is higher in some regions and countries, as well as in some subpopulations such as people who inject drugs, prisoners, or people living with HIV. In 2017, an estimated 580,000 people died from HCV, largely because of long-term complications of the disease. The advent of direct-acting antivirals (DAAs), which are highly effective in treating the infection and are well tolerated, led the World Health Organization (WHO) in 2016 to call for the eliminat...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2020 Category: Research Authors: Lazarus, J. V., Roel, E., Elsharkawy, A. M. Tags: Hepatitis C Viruses: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[PERSPECTIVES] Genetic Counseling and Genome Sequencing in Pediatric Rare Disease
Both genome sequencing (GS) and exome sequencing (ES) have proven to be revolutionary in the diagnosis of pediatric rare disease. The diagnostic potential and increasing affordability make GS and ES more accessible as a routine clinical test in some centers. Herein, I review aspects of rare disease in pediatrics associated with the use of genomic technologies with an emphasis on the benefits and limitations of both ES and GS, complexities of variant classification, and the importance of genetic counseling. Indications for testing, the role of genetic counselors in genomic test selection, and the diagnostic potential of ES ...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2020 Category: Research Authors: Elliott, A. M. Tags: Genetic Counseling: Clinical Practice and Ethical Considerations PERSPECTIVES Source Type: research

[PERSPECTIVES] Structural Mechanisms of PTEN Regulation
The tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN) is a tightly regulated enzyme responsible for dephosphorylating the progrowth lipid messenger molecule phosphatidylinositol 3,4,5-trisphosphate (PIP3) on the plasma membrane. The carboxy-terminal tail (CTT) of PTEN is key for regulation of the enzyme. When phosphorylated, the unstructured CTT interacts with the phosphatase-C2 superdomain to inactivate the enzyme by preventing membrane association. PTEN mutations associated with cancer also inactivate the enzyme. Alternate translation-initiation sites generate extended isoforms of PTEN, such as PTEN...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2020 Category: Research Authors: Masson, G. R., Williams, R. L. Tags: The PTEN Family PERSPECTIVES Source Type: research

[PERSPECTIVES] The Genetics and Mechanisms of T-Cell Acute Lymphoblastic Leukemia
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy derived from early T-cell progenitors. The recognition of clinical, genetic, transcriptional, and biological heterogeneity in this disease has already translated into new prognostic biomarkers, improved leukemia animal models, and emerging targeted therapies. This work reviews our current understanding of the molecular mechanisms of T-ALL. (Source: Cold Spring Harbor perspectives in medicine)
Source: Cold Spring Harbor perspectives in medicine - March 1, 2020 Category: Research Authors: Gianni, F., Belver, L., Ferrando, A. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights PERSPECTIVES Source Type: research

[PERSPECTIVES] Neural Control of Inflammation: Bioelectronic Medicine in Treatment of Chronic Inflammatory Disease
Inflammation is important for antimicrobial defense and for tissue repair after trauma. The inflammatory response and its resolution are both active processes that must be tightly regulated to maintain homeostasis. Excessive inflammation and nonresolving inflammation cause tissue damage and chronic disease, including autoinflammatory and cardiovascular diseases. An improved understanding of the cellular and molecular mechanisms that regulate inflammation has supported development of novel therapies for several inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease. Many of the specific anticyt...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2020 Category: Research Authors: Eberhardson, M., Tarnawski, L., Centa, M., Olofsson, P. S. Tags: Bioelectronic Medicine PERSPECTIVES Source Type: research

[PERSPECTIVES] Bioelectronic Medicine: From Preclinical Studies on the Inflammatory Reflex to New Approaches in Disease Diagnosis and Treatment
Bioelectronic medicine is an evolving field in which new insights into the regulatory role of the nervous system and new developments in bioelectronic technology result in novel approaches in disease diagnosis and treatment. Studies on the immunoregulatory function of the vagus nerve and the inflammatory reflex have a specific place in bioelectronic medicine. These studies recently led to clinical trials with bioelectronic vagus nerve stimulation in inflammatory diseases and other conditions. Here, we outline key findings from this preclinical and clinical research. We also point to other aspects and pillars of interdiscip...
Source: Cold Spring Harbor perspectives in medicine - March 1, 2020 Category: Research Authors: Pavlov, V. A., Chavan, S. S., Tracey, K. J. Tags: Bioelectronic Medicine PERSPECTIVES Source Type: research

[TECHNIQUES] PTEN Mouse Models of Cancer Initiation and Progression
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is one of the most frequently mutated, deleted, and functionally inactivated tumor suppressor genes in human cancer. PTEN is found mutated both somatically and in the germline of patients with PTEN hamartoma tumor syndrome (PHTS). PTEN encodes a dual lipid and protein phosphatase that dephosphorylates the lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3), in turn negatively regulating the oncogenic PI3K-AKT pathway, a key proto-oncogenic player in cancer development and progression. Because of importance of PTEN in tumorigenesis, a large number of sophistic...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2020 Category: Research Authors: Lee, Y.-R., Pandolfi, P. P. Tags: The PTEN Family TECHNIQUES Source Type: research

[PERSPECTIVES] Challenges and Promise of a Hepatitis C Virus Vaccine
An estimated 1.5–2 million new hepatitis C virus (HCV) infections occur globally each year. Critical to the World Health Organization's (WHO) HCV elimination strategy is an 80% reduction in incidence of HCV infections by 2030. However, even among high-income countries, few are on target to achieve the WHO's incident infection-reduction goal. A preventative vaccine could have a major impact in achieving incidence-reduction targets globally. However, barriers to HCV vaccine development are significant and include at-risk populations that are often marginalized: viral diversity, limited options for testing HCV vaccines,...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2020 Category: Research Authors: Cox, A. L. Tags: Hepatitis C Viruses: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[PERSPECTIVES] Hepatitis C Virus Entry: Protein Interactions and Fusion Determinants Governing Productive Hepatocyte Invasion
Hepatitis C virus (HCV) entry is among the best-studied uptake processes for human pathogenic viruses. Uptake follows a spatially and temporally tightly controlled program. Numerous host factors including proteins, lipids, and glycans promote productive uptake of HCV particles into human liver cells. The virus initially attaches to surface proteoglycans, lipid receptors such as the scavenger receptor BI (SR-BI), and to the tetraspanin CD81. After lateral translocation of virions to tight junctions, claudin-1 (CLDN1) and occludin (OCLN) are essential for entry. Clathrin-mediated endocytosis engulfs HCV particles, which fuse...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2020 Category: Research Authors: Gerold, G., Moeller, R., Pietschmann, T. Tags: Hepatitis C Viruses: The Story of a Scientific and Therapeutic Revolution PERSPECTIVES Source Type: research

[PERSPECTIVES] PTEN in Chromatin Remodeling
The tumor suppressor phosphatase and tension homolog (PTEN) is frequently mutated in human cancers, and it functions in multiple ways to safeguard cells from tumorigenesis. In the cytoplasm, PTEN antagonizes the PI3K/AKT pathway and suppresses cellular proliferation and survival. In the nucleus, PTEN is indispensable for the maintenance of genomic stability. In addition, PTEN loss leads to extensive changes in gene expression at the transcriptional level. The linker histone H1, generally considered as a transcriptional repressor, binds to the nucleosome to form a structure named the chromatosome. The dynamics between H1 an...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2020 Category: Research Authors: Yang, J., Yin, Y. Tags: The PTEN Family PERSPECTIVES Source Type: research

[PERSPECTIVES] Acute Megakaryocytic Leukemia
Acute megakaryoblastic leukemia (AMKL) is a rare malignancy affecting megakaryocytes, platelet-producing cells that reside in the bone marrow. Children with Down syndrome (DS) are particularly prone to developing the disease and have a different age of onset, distinct genetic mutations, and better prognosis as compared with individuals without DS who develop the disease. Here, we discuss the contributions of chromosome 21 genes and other genetic mutations to AMKL, the clinical features of the disease, and the differing features of DS- and non-DS-AMKL. Further studies elucidating the role of chromosome 21 genes in this dise...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2020 Category: Research Authors: McNulty, M., Crispino, J. D. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights PERSPECTIVES Source Type: research

[PERSPECTIVES] The Molecular Genetics of Myeloproliferative Neoplasms
Activated JAK-STAT signaling is central to the pathogenesis of BCR-ABL-negative myeloproliferative neoplasms (MPNs) and occurs as a result of MPN phenotypic driver mutations in JAK2, CALR, or MPL. The spectrum of concomitant somatic mutations in other genes has now largely been defined in MPNs. With the integration of targeted next-generation sequencing (NGS) panels into clinical practice, the clinical significance of concomitant mutations in MPNs has become clearer. In this review, we describe the consequences of concomitant mutations in the most frequently mutated classes of genes in MPNs: (1) DNA methylation pathways, (...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2020 Category: Research Authors: Marneth, A. E., Mullally, A. Tags: Leukemia and Lymphoma: Molecular and Therapeutic Insights PERSPECTIVES Source Type: research

[TECHNIQUES] Noninvasive Neuromodulation of Peripheral Nerve Pathways Using Ultrasound and Its Current Therapeutic Implications
This review describes work from several research groups in which ultrasound is being used to target the peripheral nervous system and perform neuromodulation noninvasively. Although these techniques are in their infancy compared to implant-based and electrical nerve stimulation, if successful this new noninvasive method for neuromodulation could solve many of the challenges facing the field of bioelectronic medicine. The work outlined herein shows results in which two different (potentially therapeutic) targets are stimulated, a neuroimmune pathway within the spleen and a nutrient/sensory pathway within the liver. Both dat...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2020 Category: Research Authors: Puleo, C., Cotero, V. Tags: Bioelectronic Medicine TECHNIQUES Source Type: research

[TECHNIQUES] Vagus Nerve Stimulation and the Cardiovascular System
The vagus nerve plays an important role in maintaining physiological homeostasis, which includes reflex pathways that regulate cardiac function. The link between vagus nerve activity and the high-frequency component of heart rate variability (HRV) has been well established, correlating with vagal tone. Recently, vagus nerve stimulation (VNS) has been investigated as a therapeutic for a multitude of diseases, such as treatment-resistant epilepsy, rheumatoid arthritis, Crohn's disease, and asthma. Because of the vagus nerve's innervation of the heart, VNS has been identified as a potential therapy for cardiovascular disorder...
Source: Cold Spring Harbor perspectives in medicine - February 2, 2020 Category: Research Authors: Capilupi, M. J., Kerath, S. M., Becker, L. B. Tags: Bioelectronic Medicine TECHNIQUES Source Type: research