Simulated Microgravity Impairs Cardiac Autonomic Neurogenesis from Neural Crest Cells.

Microgravity-induced alterations in the autonomic nervous system (ANS) contribute to derangements in both the mechanical and electrophysiological function of the cardiovascular system, leading to severe symptoms in humans following space travel. Because the ANS forms embryonically from neural crest (NC) progenitors, we hypothesized that microgravity can impair NC-derived cardiac structures. Accordingly, we conducted in vitro simulated microgravity experiments employing NC genetic lineage tracing in mice with cKit, Isl1nLacZ, and Wnt1-Cre reporter alleles.

Induction of endogenous retroelements as a potential mechanism for mouse-specific drug-induced carcinogenicity.

A number of chemical compounds have been shown to induce liver tumors in mice but not in other species. While several mechanisms for this species-specific tumorigenicity have been proposed, no definitive mechanism has been established. We examined the effects of the nongenotoxic rodent hepatic carcinogen, WY-14,643, in male mice from a high liver tumor susceptible strain (C3H/HeJ), and from a low tumor susceptible strain (C57BL/6).

The landscape of BRAF transcript and protein variants in human cancer.

Background: The BRAF protein kinase is widely studied as a cancer driver and therapeutic target. However, the regulation of its expression is not completely understood.

Results: Taking advantage of the RNA-seq data of more than 4800 patients belonging to 9 different cancer types, we show that BRAF mRNA exists as a pool of 3 isoforms (reference BRAF, BRAF-X1, and BRAF-X2) that differ in the last part of their coding sequences, as well as in the length (BRAF-ref: 76 nt; BRAF-X1 and BRAF-X2: up to 7 kb) and in the sequence of their 3'UTRs.

Emerging Putative Associations between Non-Coding RNAs and Protein-Coding Genes in Neuropathic Pain: Added Value from Reusing Microarray Data.

Regeneration of injured nerves is likely occurring in the peripheral nervous system, but not in the central nervous system. Although protein-coding gene expression has been assessed during nerve regeneration, little is currently known about the role of non-coding RNAs (ncRNAs). This leaves open questions about the potential effects of ncRNAs at transcriptome level.

Non-coding RNAs profiling in head and neck cancers.

The majority of studies on human cancers published to date focus on coding genes. More recently, however, non-coding RNAs (ncRNAs) are gaining growing recognition as important regulatory components. Here we characterise the ncRNA landscape in 442 head and neck squamous cell carcinomas (HNSCs) from the cancer genome atlas (TCGA).

Integrative analysis of cancer imaging readouts by networks.

Cancer is a multifactorial and heterogeneous disease. The corresponding complexity appears at multiple levels: from the molecular and the cellular constitution to the macroscopic phenotype, and at the diagnostic and therapeutic management stages. The overall complexity can be approximated to a certain extent, e.

Identification of potential therapeutic targets in a model of neuropathic pain.

Neuropathic pain (NP) is caused by damage to the nervous system, resulting in dysfunction and aberrant pain. The cellular functions (e.g.

Comparative analysis of genome sequences from four strains of the Buchnera aphidicola Mp endosymbion of the green peach aphid, Myzus persicae.

Background: Myzus persicae, the green peach aphid, is a polyphagous herbivore that feeds from hundreds of species of mostly dicot crop plants. Like other phloem-feeding aphids, M. persicae rely on the endosymbiotic bacterium, Buchnera aphidicola (Buchnera Mp), for biosynthesis of essential amino acids and other nutrients that are not sufficiently abundant in their phloem sap diet.

Viral expression associated with gastrointestinal adenocarcinomas in TCGA high-throughput sequencing data.

Background: Up to 20% of cancers worldwide are thought to be associated with microbial pathogens, including bacteria and viruses. The widely used methods of viral infection detection are usually limited to a few a priori suspected viruses in one cancer type. To our knowledge, there have not been many broad screening approaches to address this problem more comprehensively.

MicroRNA-20a constrains p300-driven myocardial angiogenic transcription by direct targeting of p300.

Objective: To characterize downstream effectors of p300 acetyltransferase in the myocardium.

Background: Acetyltransferase p300 is a central driver of the hypertrophic response to increased workload, but its biological targets and downstream effectors are incompletely known.

Methods And Results: Mice expressing a myocyte-restricted transgene encoding acetyltransferase p300, previously shown to develop spontaneous hypertrophy, were observed to undergo robust compensatory blood vessel growth together with increased angiogenic gene expression.

Characteristics of cross-hybridization and cross-alignment of expression in pseudo-xenograft samples by RNA-Seq and microarrays.

Background: Exploring stromal changes associated with tumor growth and development is a growing area of oncologic research. In order to study molecular changes in the stroma it is recommended to separate tumor tissue from stromal tissue. This is relevant to xenograft models where tumors can be small and difficult to separate from host tissue.

MicroRNA expression in alpha and beta cells of human pancreatic islets.

microRNAs (miRNAs) play an important role in pancreatic development and adult β-cell physiology. Our hypothesis is based on the assumption that each islet cell type has a specific pattern of miRNA expression. We sought to determine the profile of miRNA expression in α-and β-cells, the main components of pancreatic islets, because this analysis may lead to a better understanding of islet gene regulatory pathways.

A clinical evaluation tool for SNP arrays, especially for autosomal recessive conditions in offspring of consanguineous parents.

Purpose: This report describes a fast online tool to accelerate and improve clinical interpretation of single nucleotide polymorphism array results for diagnostic purposes, when consanguinity or inbreeding is identified.

Methods: We developed a web-based program that permits entry of regions of homozygosity and, using OMIM, UCSC, and NCBI databases, retrieves genes within these regions as well as their associated autosomal recessive disorders. Relevant OMIM Clinical Synopses can be searched, using key clinical terms permitting further filtering for candidate genes and disorders.

Inflammation-Mediated Regulation of MicroRNA Expression in Transplanted Pancreatic Islets.

Nonspecific inflammation in the transplant microenvironment results in β-cell dysfunction and death influencing negatively graft outcome. MicroRNA (miRNA) expression and gene target regulation in transplanted islets are not yet well characterized. We evaluated the impact of inflammation on miRNA expression in transplanted rat islets.

GenSensor Suite: A Web-Based Tool for the Analysis of Gene and Protein Interactions, Pathways, and Regulation.

The GenSensor Suite consists of four web tools for elucidating relationships among genes and proteins. GenPath results show which biochemical, regulatory, or other gene set categories are over- or under-represented in an input list compared to a background list. All common gene sets are available for searching in GenPath, plus some specialized sets.

Heterogeneity in SDF-1 expression defines the vasculogenic potential of adult cardiac progenitor cells.

Rationale: The adult myocardium has been reported to harbor several classes of multipotent progenitor cells (CPCs) with tri-lineage differentiation potential. It is not clear whether c-kit+CPCs represent a uniform precursor population or a more complex mixture of cell types.

Objective: To characterize and understand vasculogenic heterogeneity within c-kit+presumptive cardiac progenitor cell populations.

Identifying consensus disease pathways in Parkinson's disease using an integrative systems biology approach.

Parkinson's disease (PD) has had six genome-wide association studies (GWAS) conducted as well as several gene expression studies. However, only variants in MAPT and SNCA have been consistently replicated. To improve the utility of these approaches, we applied pathway analyses integrating both GWAS and gene expression.

MicroRNA signature of the human developing pancreas.

Background: MicroRNAs are non-coding RNAs that regulate gene expression including differentiation and development by either inhibiting translation or inducing target degradation. The aim of this study is to determine the microRNA expression signature during human pancreatic development and to identify potential microRNA gene targets calculating correlations between the signature microRNAs and their corresponding mRNA targets, predicted by bioinformatics, in genome-wide RNA microarray study.

Results: The microRNA signature of human fetal pancreatic samples 10-22 weeks of gestational age (wga), was obtained by PCR-based high throughput screening with Taqman Low Density Arrays.

Glucocorticoid receptor polymorphisms and intraocular pressure response to intravitreal triamcinolone acetonide.

Background: Elevation of intraocular pressure (IOP) following injection of intravitreal triamcinolone acetonide (IVTA) is an important clinical problem. The etiology of the steroid response is poorly understood, although a genetic determinant has long been suspected. We performed a pharmacogenomic association study with glucocorticoid receptor polymorphisms.

Electronically subtracting expression patterns from a mixed cell population.

Motivation: Biological samples frequently contain multiple cell-types that each can play a crucial role in the development and/or regulation of adjacent cells or tissues. The search for biomarkers, or expression patterns of, one cell-type in those samples can be a complex and time-consuming process. Ordinarily, extensive laboratory bench work must be performed to separate the mixed cell population into its subcomponents, such that each can be accurately characterized.

A genome-wide study of lupus: preliminary analysis and data release.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which genetics is one of the underlying risk factors. Complicating the analysis of SLE is the fact that the phenotype is heterogeneous, with variations in clinical features, and subgroups are associated with a variety of different autoantibodies. Many association studies of candidate genes as well as linkage studies have generated significant results, highlighting the multigenetic component of the disease.

Developing combinatorial multi-component therapies (CMCT) of drugs that are more specific and have fewer side effects than traditional one drug therapies.

Drugs designed for a specific target are always found to have multiple effects. Rather than hope that one bullet can be designed to hit only one target, nonlinear interactions across genomic and proteomic networks could be used to design Combinatorial Multi-Component Therapies (CMCT) that are more targeted with fewer side effects. We show here how computational approaches can be used to predict which combinations of drugs would produce the best effects.

An integrated in silico gene mapping strategy in inbred mice.

In recent years in silico analysis of common laboratory mice has been introduced and subsequently applied, in slightly different ways, as a methodology for gene mapping. Previously we have demonstrated some limitation of the methodology due to sporadic genetic correlations across the genome. Here, we revisit the three main aspects that affect in silico analysis.