Caused by a polyglutamine expansion in the huntingtin protein, Huntington's disease leads to striatal degeneration via the transcriptional dysregulation of a number of genes, including those involved in mitochondrial biogenesis. Here we show that transglutaminase 2, which is upregulated in HD, exacerbates transcriptional dysregulation by acting as a selective corepressor of nuclear genes; transglutaminase 2 interacts directly with histone H3 in the nucleus. In a cellular model of HD, transglutaminase inhibition de-repressed two established regulators of mitochondrial function, PGC-1α and cytochrome c and reversed susceptibility of human HD cells to the mitochondrial toxin, 3-nitroproprionic acid; however, protection mediated by transglutaminase inhibition was not associated with improved mitochondrial bioenergetics. A gene microarray analysis indicated that transglutaminase inhibition normalized expression of not only mitochondrial genes but also 40% of genes that are dysregulated in HD striatal neurons, including chaperone and histone genes. Moreover, transglutaminase inhibition attenuated degeneration in a Drosophila model of HD and protected mouse HD striatal neurons from excitotoxicity. Altogether these findings demonstrate that selective TG inhibition broadly corrects transcriptional dysregulation in HD and defines a novel HDAC-independent epigenetic strategy for treating neurodegeneration.

Background-Zinc transporter-8 (ZnT8) was recently identified as a novel autoantigen in human type 1 diabetes (T1D). Autoantibody to ZnT8 (ZnT8A) were detected in up to 80% of newonset T1D and 26% of T1D patients otherwise classified as negative on the basis of existing markers. Since no data of ZnT8A in Chinese has been reported, we aim to evaluate the utility of ZnT8A for diagnosis of autoimmune T1D in Chinese relative to other autoantibody markers.

Interactions among microbes and stratification across depths are both believed to be important drivers of microbial communities, though little is known about how microbial associations differ between and across depths. We have monitored the free-living microbial community at the San Pedro Ocean Time-series station, monthly, for a decade, at five different depths: 5 m, the deep chlorophyll maximum layer, 150 m, 500 m and 890 m (just above the sea floor). Here, we introduce microbial association networks that combine data from multiple ocean depths to investigate both within-and between-depth relationships, sometimes time-lagged, among microbes and environmental parameters. The euphotic zone, deep chlorophyll maximum and 890 m depth each contain two negatively correlated 'modules' (groups of many inter-correlated bacteria and environmental conditions) suggesting regular transitions between two contrasting environmental states. Two-thirds of pairwise correlations of bacterial taxa between depths lagged such that changes in the abundance of deeper organisms followed changes in shallower organisms. Taken in conjunction with previous observations of seasonality at 890 m, these trends suggest that planktonic microbial communities throughout the water column are linked to environmental conditions and/or microbial communities in overlying waters. Poorly understood groups including Marine Group A, Nitrospina and AEGEAN-169 clades contained taxa that showed diverse association patterns, suggesting these groups contain multiple ecological species, each shaped by different factors, which we have started to delineate. These observations build upon previous work at this location, lending further credence to the hypothesis that sinking particles and vertically migrating animals transport materials that significantly shape the time-varying patterns of microbial community composition.

Colorectal cancer (CRC) is the third most common cancer worldwide. Its incidence is still increasing, and the mortality rate is high. New therapeutic and prognostic strategies are urgently needed. It became increasingly recognized that the gut microbiota composition differs significantly between healthy people and CRC patients. Thus, identifying the difference between gut microbiota of the healthy people and CRC patients is fundamental to understand these microbes' functional roles in the development of CRC. We studied the microbial community structure of a CRC metagenomic dataset of 156 patients and healthy controls, and analyzed the diversity, differentially abundant bacteria, and co-occurrence networks. We applied a modified zero-inflated lognormal (ZIL) model for estimating the relative abundance. We found that the abundance of genera: Anaerostipes, Bilophila, Catenibacterium, Coprococcus, Desulfovibrio, Flavonifractor, Porphyromonas, Pseudoflavonifractor , and Weissella was significantly different between the healthy and CRC groups. We also found that bacteria such as Streptococcus, Parvimonas, Collinsella, and Citrobacter were uniquely co-occurring within the CRC patients. In addition, we found that the microbial diversity of healthy controls is significantly higher than that of the CRC patients, which indicated a significant negative correlation between gut microbiota diversity and the stage of CRC. Collectively, our results strengthened the view that individual microbes as well as the overall structure of gut microbiota were co-evolving with CRC.