Volume 21 Issue 11, November 2015

Neutralization breadth is thought to be an important feature of an effective vaccine against HIV-1. A study in one individual has now identified the specific viral variant that engaged the necessary antibody precursor, as well as the viral immunotypes that drove neutralization breadth, improving understanding of how to mimic this process with a vaccine.

Cancer cachexia leads to involuntary weight loss resulting from the atrophy of skeletal muscle and adipose tissues. Now, in metastatic mouse models of cancer, investigators reveal a cross talk pathway between bone and muscle that provides a new understanding of wasting in advanced cancers.

A new study using human pluripotent stem cell (hPSC)-derived human pancreatic organoids to model neoplastic transformation and cancer-derived human pancreatic tumor organoids for drug testing provides new personalized approaches to modeling and treating this malignancy.

Chronic pain affects millions of people worldwide. A new study presents a promising therapeutic strategy in which Toll-like receptor (TLR) 5 stimulation enables the analgesic compound, QX-314, to specifically enter and silence large fiber sensory neurons, which convey pain in the setting of injury.

Maite Huarte discusses our current understanding of the impact of long noncoding RNAs on tumor growth and progression, and how this knowledge might be translated into new therapeutic approaches.

Metastasis-mediated osteolysis results in excess release of TGF-β that, in turn, leads to muscle weakness.

Hair follicle–derived cytokines control the tropism and retention of memory T cells in the skin and promote lymphoma.

MicroRNA-148a, whose expression is regulated by the transcription factor SREBP1c, controls LDL and HDL metabolism through direct targeting of the genes encoding the LDL receptor and the cholesterol transporter ABCA1.

From a systematic analysis of genome-wide association studies of blood lipid levels, Wagschal et al. identify several miRNAs that target key proteins involved in cholesterol and lipid metabolism, including the LDL receptor and the ABCA1 cholesterol transporter.

Induction of cardiac contractility, although desirable for restoring heart function, often has long-term detrimental effects. From studies on RKIP, an upstream regulator of β-adrenergic receptor signaling, Schmid et al. show that cardiac contractility in mice can be increased in a well-tolerated manner through the balanced activation of the β1 and β2 subtypes of the adrenergic receptor.

Factors traditionally associated with coagulation and inflammation, such as thrombin, PAR1, aPC and EPCR, also independently control the nitric oxide production switch in hematopoietic stem cells, thereby regulating EPCR-expressing stem cell adhesion and retention in the bone marrow or recruitment to the blood.

The authors implement a collection of patient-derived xenograft tumors to test cancer drug responses.

Toll-like receptor 5 (TLR5) expression is found to be enriched in mouse dorsal root ganglion (DRG) A-fiber neurons known to mediate mechanical allodynia, a form of chronic neuropathic pain. Selective silencing of both mouse and human DRG A-fiber neurons is achieved by co-application of the TLR5 ligand flagellin and the lidocaine derivative QX-314, which is also sufficient to reverse mechanical allodynia in three different mouse models of chronic neuropathic pain.

Penny Moore and colleagues identify viral variants from an HIV-1 infected individual that drove maturation of the antibody response from an unmutated common ancestor, ultimately resulting in both broadly neutralizing and strain-specific antibody sublineages.

Blocking alternative activation of p38 in tumor-infiltrating CD4⁺ T cells reduces proinflammatory cytokine production and inhibits pancreatic cancer growth in mice.

BAP1 regulation of EZH2 provides therapeutic opportunities in cancer.

An international consortium of colorectal cancer researchers undertakes a large-scale data sharing project to achieve a consensus molecular classification of colorectal cancers.

A pipeline incorporating genetic fine mapping, epigenome editing, and genome editing enables functional analysis of disease-associated SNPs located in non-protein-coding regions of the genome.

Human pluripotent stem cells can be differentiated into exocrine pancreas progenitor organoids, allowing studies of development and pancreatic cancer modeling.