Volume 22 Issue 11, November 2016

A new study presents a protocol to differentiate human induced pluripotent stem cells (iPSCs) into microglia that closely resemble their in vivo counterparts. These cells offer an exciting new tool for learning more about the role of microglia in disease.

Misfolded and hyperphosphorylated forms of the microtubule-associated protein tau are thought to be responsible for some degree of neurodegeneration. The demonstration of a novel toxic cleavage of tau by caspase-2 opens up new therapeutic avenues.

A recent study confirms an association between vessel co-option and resistance to bevacizumab, an anti-vascular endothelial growth factor-A (VEGFA) antibody, in patients with liver metastases. The authors suggest a combined therapeutic strategy that reduces co-option in mice.

Aberrant injury responses in the distal lung likely underpin the development of idiopathic pulmonary fibrosis (IPF). A recent study shows that defective Toll-like receptor 4 (TLR4)-mediated hyaluronan binding impairs alveolar type 2 cell renewal, which may contribute to a dysregulated lung-injury response in IPF.

From organoids to population-level studies, mental health research has begun to crack long-standing mysteries. Longitudinal investigations into brain and cognitive development among adolescents, such as the forthcoming 10,000-person ABCD project, will help to mature the field.

Recent studies have led to the identification of genetic loci that are shared between psychiatric disorders. Here O’Donovan and Owen argue that it is unlikely that risk alleles exist that are singular to any one such disorder.

Psychiatric disorders are difficult to model owing to their inherent complexity and heterogeneity. This Perspective focuses on the use of 3D brain organoids in modeling these disorders, considering both their advantages and their limitations.

The developmental trajectories of neuropsychiatric disorders suggest that early life events might contribute substantially to disease. Here the author discusses the potential to treat within these critical time windows of development to alter disease course.

Recent evidence indicates that one of the underlying mechanisms in the pathogenesis of neuropsychiatric disorders is dysregulated dentate gyrus neurogenesis. Here the authors present evidence supporting this hypothesis and suggest therapeutic avenues.

Abi-Dargham and Horga discuss the challenges of developing and standardizing brain-imaging technologies to aid with the diagnosis and treatment of psychiatric disorders.

New animal models of Zika virus (ZIKV) infection are imperative to accelerating efforts to treat or prevent disease in humans. Adams Waldorf et al. now report that ZIKV infection of a pregnant female pigtailed macaque caused brain lesions in the developing fetus, suggesting that this model may be useful for understanding ZIKV-associated congenital abnormalities in humans.

Broadly neutralizing antibodies (bnAbs) develop in a minority of HIV-infected individuals. Analyzing data from more than 4,000 infected individuals, Alexandra Trkola and colleagues identify viral, host and disease factors associated with the development of bNAbs that may inform future vaccine design.

Caspase-2-mediated cleavage of tau is shown to generate a fibrillation-resistant truncation product (Δtau314) that contributes to the missorting of tau into dendritic spines, synaptic dysfunction, neurodegeneration and cognitive impairments in mice.

In humans and rodent models, commensal gut bacteria contribute to post-stroke infection. Experimental stroke in rodents causes gut barrier dysfunction and permeability, enabling translocation and dissemination of host gut microbiota.

Reduced hyaluronan–TLR4 signaling in a stem cell population of the lung contributes to a lack of renewal of these cells and promotes fibrosis in patients with idiopathic pulmonary fibrosis.

Poor responses of liver metastases to the anti-angiogenic agent bevacizumab in patients with colorectal and breast cancer correlate with tumor co-option of pre-existing blood vessels, a mechanism of tumor resistance that might be targeted by the inhibition of cancer cell motility.

In triple-negative breast cancer, the kinase PIM1, which is highly expressed, functions through the transcription factor c-MYC to promote tumor cell survival and growth.

Whole-genome sequencing identified recurrent fusions involving the MET oncogene, and MET inhibitors suppressed tumor growth in mouse models and in a human patient.

In triple-negative breast cancer, the PIM1 kinase is highly expressed, acts to promote tumor cell survival and growth, and increases MYC transcriptional activity.

Dietary zinc supplements are in common use, but their effect on infection is unclear. New findings now show that excess dietary zinc reduces the diversity of the gut microbiota and increases the susceptibility of antibiotic-treated mice to Clostridium difficile infection.

In a mouse model of traumatic brain injury, treatment with a carbon-monoxide-releasing molecule is shown to reduce pericyte cell death and promote neurogenesis, leading to an amelioration of neurological deficits.

Systematic analysis of more than 5,900 human tumor exomes yields a new genomic classifier of microsatellite instability and insight into its prevalence and biological implications.

In a new mouse model of multiple myeloma, mice expressing the human versions of six proteins important for hematopoietic function were able to support the growth of primary human multiple myeloma xenografts, including both preneoplastic and malignant plasma cells.

A protocol is developed to enable the differentiation of microglial-like cells from human pluripotent stem cells, which are shown to resemble primary human microglia, integrate into 3D neuronal cultures, and perform phagocytic and injury-response functions.