Volume 22 Issue 5, May 2016

A recent study identifies differences in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes from patients with breast cancer who were treated with doxorubicin and either did or did not develop cardiotoxicity. The results open up new avenues for the development of personalized therapy and the prevention of cardiotoxicity.

A new study shows in mice that tumor necrosis factor (TNF) superfamily member 11 (TNFSF11, also known as RANKL), which stimulates osteoclasts to remove bone, binds to the G-protein-coupled receptor LGR4 to prevent excessive bone removal. In mouse models of osteoporosis, a recombinant LGR4 ectodomain reduces bone loss.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive stromal component that hinders treatment. A new study shows how the genetic identity of pancreatic tumors might influence the physical properties of the associated stroma to promote tumor progression.

Grafting of caudalized rodent or human neural progenitor cells into sites of spinal cord injury enables true regeneration of damaged corticospinal axons in rodents. Regenerating axons form functional synapses within the graft, can extend beyond the lesion site, and help to support functional motor recovery.

ROR-γ antagonists suppress androgen receptor expression and growth of prostate tumors, but not of androgen-responsive healthy tissue, in preclinical models.

Impaired TGF-β signaling due to SMAD4 mutation in PDAC tumors initiates a STAT3-dependent signaling cascade that leads to increased stromal stiffening and disease progression.

The intestinal microbiota signals through epithelial cells to activate calcineurin and NFAT, driving proliferation of cancer stem cells and the development of colorectal cancer.

Alterations in the gut microbiota affect stroke outcomes via modulation of T cells, suggesting a gut-brain axis linking commensal microbes with the CNS.

The mucosal adjuvant activity of cholera toxin depends on the microbiota, which signals through Nod2 on CD11c⁺ cells.

Using proteomic analyses, Eric Rubin, Véronique Dartois and colleagues show that tuberculosis granulomas have spatially segregated protein compositions that compartmentalize pro- and anti-inflammatory responses to distinct regions.

LGR4 has been identified as a new receptor for RANKL in bone cells where it opposes RANK signaling to inhibit osteoclasts differentiation, and its therapeutic targeting promotes reduced bone loss in three mouse models of osteoporosis.

The chemotherapeutic agent doxorubicin causes cardiac injury in a subset of cancer patients. This variable clinical response to doxorubicin treatment can be recapitulated in vitro by using cardiomyocytes derived from patient-specific induced pluripotent cells.

Mark Kay and colleagues report that liver toxicity due to high doses of shRNAs is triggered by a decrease in an isoform of the abundant liver microRNA, miR-122.

Choi et al. identify a Bacteroides fragilis–encoded protease that activates the bacterial enterotoxin and is important for bloodstream infection in mice.