News & Comment

Recent advances in the generation of multipotent and expandable induced neural stem cells are exciting. They not only hold great promises for potential clinical applications but may also open up a new era for neural stem cell research in the near future.

A recent paper suggests that reduced exposure to germs results in the expansion of a cell type called natural killer T cells, which predisposes to colitis and asthma. Such a scenario could explain the Hygiene Hypothesis, which has been a puzzle for decades.

It is not clearly understood what happens at the interface between normal and transformed epithelial cells at the first step of carcinogenesis. A recent study reveals that the organized epithelial structure suppresses clonal expansion of transformed cells. Translocation from the epithelium or perturbation of intercellular adhesions may be required for transformed cells to evade the suppressive environments.

The cellular response to amino acids is controlled at the molecular level by TORC1. While many of the elements that participate in TORC1 signaling are known, we still have no clear idea how cells sense amino acids. Two recent studies found that leucyl-tRNA synthetase (LRS) is a leucine sensor for TORC1, in both yeast and mammalian cells.

Initial studies linking Sirtuins to longevity in yeast initiated what is now a rich vein of aging research that is full of promise and fraught with controversy. Missing was a demonstration that enhanced Sirtuin expression extends lifespan in mammals. Now Kanfi et al. provide the evidence but with an interesting plot twist – the lesser known SIRT6 is the longevity factor.

Humans can be divided into roughly three groups with distinct microbial communities in their gastro-intestinal tract. The microbiota contributes to metabolic activity in the gastro-intestinal tract of the host, but what mechanisms shape the composition of the gut microbiota, and how does a person's 'enterotype' affect metabolic processes in distant organs? Flavell and colleagues shed light on these questions by revealing an important role for inflammasomes in modulating the prevalence of colitogenic species, and by demonstrating that dysbiosis influences susceptibility to non-alcoholic steatohepatitis (NASH) and other manifestations of metabolic syndrome.

Aging is a key risk factor in neurodegenerative disease; however, little is known about cellular pathways that mediate age-associated degeneration of the brain. The Bonini lab has identified a conserved microRNA, miR-34, that plays a neuroprotective role in the aging Drosophila brain and suggests that it functions in temporal control of gene expression.

Efficient DNA damage sensing and repair is crucial to preserve genomic integrity and failure to detect or repair DNA breaks can cause mutations, contributing to the formation of tumors. One key protein required for mediating DNA repair is the tumor suppressor 53BP1. Recent studies now demonstrate the crucial role of K48-linked ubiquitination and protein degradation for 53BP1 recruitment at sites of DNA damage.

Hematopoietic stem cell transplantation remains the only curative therapy for certain genetic diseases of the hematopoietic system, including some inheritable deficiencies in red blood cells (RBC). Recent advances in induced pluripotent stem cells may open a new era for the cure of such severe genetic RBC diseases.

Tumor-associated mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes result in the loss of normal catalytic activity, the production of α-ketoglutarate (α-KG), and gain of a new activity, the production of an oncometabolite, R-2-hydroxylglutarate (R-2-HG). New evidence supports previous findings that R-2-HG acts as an antagonist of α-KG to competitively inhibit the activity of multiple α-KG-dependent dioxygenases, including both histones and DNA demethylases involved in epigenetic control of gene expression and cell differentiation, and also reveals an intriguing new facet of R-2-HG in tumorigenesis.

Histone modifications have previously been leveraged to map the locations of candidate enhancer and promoters in one dimensional genomic space. Chepelev et al. report the first Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) sequencing of a specific histone modification to systematically map long-range physical interactions among enhancer and promoters, yielding insights into the nature of these interactions.

The ORAI1 store-operated calcium channel, also known as the CRAC channel, has provided many surprises. The latest is that channel gating and ion selectivity are closely intertwined.

The prevalence of certain driver mutations in prostate cancer varies across ethnic populations. A recent study uses RNA-seq to profile the mutational landscape of prostate cancer in a Chinese population to gain additional insights on ethnic variation in this disease.

The discovery of Nongken 58S, a natural recessive photoperiod-sensitive male sterile line, served as a starting point for development of two-line hybrid rice in China. While original Nongken 58S in its japonica background is photoperiod-sensitive male sterile, after introgressing of the related locus into indica rice background the same trait become mainly temperature-sensitive male sterile. Although those photoperiod- and temperature-sensitive male sterile lines have been successfully used in two-line hybrid rice seed production, the genetic cause remained a mystery till the two recent publications, with one in Cell Research.

LRRK2 was recently identified as a major susceptibility gene for Crohn's disease (CD) by genome-wide association studies (GWAS). LRRK2 deficiency in mice confers enhanced susceptibility to experimental colitis. In this research highlight, we discuss the current understanding of LRRK2 in the context of colitis, and postulate the future directions.

BECN1 plays a central role in determining cell fate, acting as a balance point in the decision to undergo autophagy or apoptosis. Three distinct structural domains allow BECN1 to interact with several other proteins. Recent crystallographic data provide insight into the nature of the coiled-coil and evolutionarily conserved domains.

Emerging evidence suggests an involvement of nuclear pore components in the regulation of neural differentiation and aging. These findings will have far-ranging impacts on the understanding of the function of the nuclear envelope in physiological settings and in various neurological diseases.