RNAscope 2.0 Assay

Diffuse PTH expression in parathyroid tumors argues against important functional tumor subclones.

Abstract

OBJECTIVE:

Primary hyperparathyroidism is usually characterized by a monoclonal parathyroid tumor secreting excess parathyroid hormone (PTH). The main regulator of PTH secretion is calcium and the calcium-PTH set point is shifted in parathyroid tumor cells. We sought to investigate the relationship between tumor PTH and PTH mRNA expression and clinical presentation as well as regulatory factors including phosphate, vitamin D and fibroblast growth factor 23.

DESIGN:

Central nervous system disease and genital disease in harbor porpoises (Phocoena phocoena) are associated with different herpesviruses.

Herpesvirus infection causes disease of variable severity in many species, including cetaceans. However, little is known about herpesvirus infection in harbor porpoises (Phocoena phocoena), despite being widespread in temperate coastal waters of the Northern Hemisphere. Therefore, we examined harbor porpoises that stranded alive in the Netherlands, Belgium, and Germany between 2000 and 2014 for herpesvirus infection and associated disease. Porpoises that died or had to be euthanized were autopsied, and samples were collected for virological and pathological analyses.

Selective and reversible suppression of intestinal stem cell differentiation by pharmacological inhibition of BET bromodomains.

Absorptive and secretory cells of the small intestine are derived from a single population of Lgr5-expressing stem cells. While key genetic pathways required for differentiation into specific lineages have been defined, epigenetic programs contributing to this process remain poorly characterized. Members of the BET family of chromatin adaptors contain tandem bromodomains that mediate binding to acetylated lysines on target proteins to regulate gene expression.

Distribution of the c-MYC gene product in colorectal neoplasia.

AIMS:
Recent attempts to study MYC distribution in human samples have been confounded by a lack of agreement in immunohistochemical staining between antibodies targeting the N-terminal or C-terminal of the MYC protein. This aim of this study was to use a novel in situ hybridisation (ISH) approach to detect MYC mRNA in clinically relevant samples, and thereby determine the reliability of MYC targeting antibodies.

Molecular Analysis of Sarcoidosis Granulomas Reveals Antimicrobial Targets.

Sarcoidosis is a granulomatous disease of unknown etiology. Prior molecular and immunologic studies have confirmed the presence of mycobacterial virulence factors, such as catalase peroxidase (katG) and superoxide dismutase A, within sarcoidosis granulomas. Molecular analysis of granulomas can identify targets of known antibiotics classes. Currently, major antibiotics are directed against DNA synthesis, protein synthesis, and cell wall formation.

BVES regulates c-Myc stability via PP2A and suppresses colitis-induced tumourigenesis

Abstract

Objective
Blood vessel epicardial substance (BVES) is a tight junction-associated protein that regulates epithelial-mesenchymal states and is underexpressed in epithelial malignancy. However, the functional impact of BVES loss on tumourigenesis is unknown. Here we define the in vivo role of BVES in colitis-associated cancer (CAC), its cellular function and its relevance to patients with IBD.

The LINK-A lncRNA activates normoxic HIF1α signalling in triple-negative breast cancer.

Although long non-coding RNAs (lncRNAs) predominately reside in the nucleus and exert their functions in many biological processes, their potential involvement in cytoplasmic signal transduction remains unexplored. Here, we identify a cytoplasmic lncRNA, LINK-A (long intergenic non-coding RNA for kinase activation), which mediates HB-EGF-triggered, EGFR:GPNMB heterodimer-dependent HIF1α phosphorylation at Tyr 565 and Ser 797 by BRK and LRRK2, respectively.

Neural crest cell-autonomous roles of fibronectin in cardiovascular development.

The chemical and mechanical properties of extracellular matrices (ECMs) modulate diverse aspects of cellular fates; however, how regional heterogeneity in ECM composition regulates developmental programs is not well understood. We discovered that fibronectin 1 (Fn1) is expressed in strikingly non-uniform patterns during mouse development, suggesting that regionalized synthesis of the ECM plays cell-specific regulatory roles during embryogenesis. To test this hypothesis, we ablated Fn1 in the neural crest (NC), a population of multi-potent progenitors expressing high levels of Fn1.

Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion

In animals, the protein kinase C (PKC) family has expanded into diversely regulated subgroups, including the Rho family-responsive PKN kinases. Here, we describe knockouts of all three mouse PKN isoforms and reveal that PKN2 loss results in lethality at embryonic day 10 (E10), with associated cardiovascular and morphogenetic defects. The cardiovascular phenotype was not recapitulated by conditional deletion of PKN2 in endothelial cells or the developing heart. In contrast, inducible systemic deletion of PKN2 after E7 provoked collapse of the embryonic mesoderm.

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