Volume 21 Issue 9, September 2015

Disease models inform our understanding of central nervous system disorder pathogenesis and enable testing of novel therapeutics. A frank discussion of the rationale for using particular disease models, as well as their limitations, may enable comparisons between studies and facilitate drug development.

A new study identifies the RAS-MAPK pathway to be an Achilles' heel of EML4-ALK fusion-positive lung cancer and suggests that up-front combination therapy directed against both pathways can achieve sustained suppression of tumor growth.

Kidney fibrosis is a main pathological component of chronic kidney disease. Two new studies pinpoint a partial epithelial-to-mesenchymal transition as a mechanism driving the development of kidney fibrosis, thus paving the way for novel treatments of fibrosis-associated diseases.

Seven years after the launch of the Human Microbiome Project, we still lack sufficient tools to visualize the microbiome in a living host. A new study provides experimental tools to label and track live anaerobic bacteria in the microbial communities in the mouse gut and beyond.

In this Perspective, the authors discuss the currently available models for psychiatric disease modeling. They present a framework for translating new knowledge by placing more emphasis on identifying neurophysiological defects.

During renal fibrosis, epithelial cells undergo a partial epithelial-to-mesenchymal transition that can be targeted to reverse established disease.

During renal fibrosis epithelial cells undergo a partial epithelial-to-mesenchymal transition that can be targeted to reverse established disease.

GITR signaling inhibits tumor growth by inducing T_H9 cell differentiation, increasing IL-9–dependent dendritic cell function and enhancing cytotoxic T cell responses.

A meta-analysis across ten pediatric autoimmune diseases reveals shared genetic architecture and novel susceptibility loci.

The membrane protein Nogo-B, resident in the endoplasmic reticulum, acts in endothelial cells to inhibit the rate-limiting enzyme of the de novo pathway of sphingolipid biosynthesis, thereby regulating vascular function and blood pressure.

Unraveling the signaling dependencies of EMLK4-ALK fusion–driven lung cancer reveals upfront combination therapy strategies.

PCSK6 is identified as the protease that cleaves and activates the zymogen form of corin, a protease that in turn activates the natriuretic peptides that control salt balance and blood pressure.

The intracellular domain of amyloid precursor protein (AICD), generated during the processing of APP along the amyloidogenic pathway, is shown to repress transcription of the Wasf1 gene, encoding the WAVE1 protein. The reduction in WAVE1 levels inhibits cell surface trafficking of APP, thereby creating a homeostatic negative feedback circuit to limit further production of amyloid-β.

The authors find that alterations in retrotransposition can occur at different stages in the evolution of pancreatic adenocarcinoma.

Barney Graham and colleagues have developed a hemagglutinin stem–based nanoparticle as a vaccine that confers protection against different influenza strains in mice and ferrets.

Charles Serhan and colleagues report four new resolvins produced under inflammatory conditions that speed resolution of bacterial infection in mice.

The cytokine TNF-α, typically considered to have deleterious effects on the heart, can also have cardioprotective effects by inducing formation of a keratin cytoskeletal network in cardiomyocytes.

Myostatin is shown to directly promote osteoclast differentiation, and its inhibition improves arthritic bone loss in two mouse models.

Fluorescently labeled commensal microbes can be tracked in vivo, allowing visualization of host–microbiota interactions in real time.