THY-1 Cell Surface Protein and Human Cytomegalovirus Infection

This research project is to investigate the role of a cell surface protein, THY-1, as an entry mediator for Human Cytomegalovirus (HCMV) infection. Previous research suggested that HCMV attaches to THY-1 on the host cell surface through virus encoded glycoprotein gB. The glycoproteins are located on the surface of virus particles thus initiating entry and infection. The specific question is to determine if the presence of a soluble form of THY-1 protein (sTHY-1) during the onset of infection would impair HCMV infectivity, based on the hypothesis that sTHY-1 would interrupt the interaction between the infectious virion and the target cells by competing with authentic cell surface THY-1 for binding to gB. The experimental approach is to prepare a plasmid encoding sTHY-1, to introduce it into mammalian cells by transfection to express the protein, to purify the sTHY-1, and to test the purified protein using Western blot and blocking of infection assays. HCMV is a herpes virus transmitted through saliva, urine, or other body fluids. Congenital HCMV occurs when HCMV is passed from a pregnant mother to her fetus. Many people encounter HCMV in their lifetime and according to the Centers for Disease Control (CDC), 50 to 80 percent of adults who are 40 or older are infected with HCMV. For individuals with a healthy immune system, HCMV produces mild illness, and for immunocompromised individuals, HCMV has a high rate of reactivation and can cause serious disease

Next-generation sequencing using microfluidic PCR enrichment for molecular autopsy.

BACKGROUND: We aimed to determine the mutation yield and clinical applicability of "molecular autopsy" following sudden arrhythmic death syndrome (SADS) by validating and utilizing low-cost high-throughput technologies: Fluidigm Access Array PCR-enrichment with Illumina HiSeq 2000 next generation sequencing (NGS). METHODS: We validated and optimized the NGS platform with a subset of 46 patients by comparison with Sanger sequencing of coding exons of major arrhythmia risk-genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, RYR2). A combined large multi-ethnic international SADS cohort was sequenced utilizing the NGS platform to determine overall molecular yield; rare variants identified by NGS were subsequently reconfirmed by Sanger sequencing. RESULTS: The NGS platform demonstrated 100% sensitivity for pathogenic variants as well as 87.20% sensitivity and 99.99% specificity for all substitutions (optimization subset, n = 46). The positive predictive value (PPV) for NGS for rare substitutions was 16.0% (27 confirmed rare variants of 169 positive NGS calls in 151 additional cases). The overall molecular yield in 197 multi-ethnic SADS cases (mean age 22.6 ± 14.4 years, 68% male) was 5.1% (95% confidence interval 2.0-8.1%), representing 10 cases carrying pathogenic or likely pathogenic risk-mutations. CONCLUSIONS: Molecular autopsy with Fluidigm Access Array and Illumina HiSeq NGS utilizing a selected panel of LQTS/BrS and CPVT risk-genes offers moderate diagnostic yield, albeit requiring confirmatory Sanger-sequencing of mutational variants

Lung epithelial stem cells and their niches : Fgf10 takes center stage

Throughout life adult animals crucially depend on stem cell populations to maintain and repair their tissues to ensure life-long organ function. Stem cells are characterized by their capacity to extensively self-renew and give rise to one or more differentiated cell types. These powerful stem cell properties are key to meet the changing demand for tissue replacement during normal lung homeostasis and regeneration after lung injury. Great strides have been made over the last few years to identify and characterize lung epithelial stem cells as well as their lineage relationships. Unfortunately, knowledge on what regulates the behavior and fate specification of lung epithelial stem cells is still limited, but involves communication with their microenvironment or niche, a local tissue environment that hosts and influences the behaviors or characteristics of stem cells and that comprises other cell types and extracellular matrix. As such, an intimate and dynamic epithelial-mesenchymal cross-talk, which is also essential during lung development, is required for normal homeostasis and to mount an appropriate regenerative response after lung injury. Fibroblast growth factor 10 (Fgf10) signaling in particular seems to be a well-conserved signaling pathway governing epithelial-mesenchymal interactions during lung development as well as between different adult lung epithelial stem cells and their niches. On the other hand, disruption of these reciprocal interactions leads to a dysfunctional epithelial stem cell-niche unit, which may culminate in chronic lung diseases such as chronic obstructive pulmonary disease (COPD), chronic asthma and idiopathic pulmonary fibrosis (IPF)

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Role of social support in lifestyle-focused weight management interventions.

Contains fulltext : 48515.pdf (publisher's version ) (Closed access)Social support is important to achieve beneficial changes in risk factors for disease, such as overweight and obesity. This paper presents the theoretical and practical framework for social support, and the mechanisms by which social support affects body weight. The theoretical and practical framework is supported with a literature review addressing studies involving a social support intervention for weight loss and weight loss maintenance. A major aspect in social support research and practice is the distinction between structural and functional support. Structural support refers to the availability of potential support-givers, while functional support refers to the perception of support. Interventions often affect structural support, for example, through peer groups, yet functional support shows a stronger correlation with health. Although positive correlations between social support and health have been shown, social support may also counteract health behaviour change. Most interventions discussed in this review showed positive health outcomes. Surprisingly, social support was clearly defined on a practical level in hardly any studies, and social support was assessed as an outcome variable in even fewer studies. Future social support intervention research would benefit from clear definitions of social support, a clear description of the intended mechanism of action and the actual intervention, and the inclusion of perceived social support as a study outcome