Recent studies on enzymes and reader proteins for histone crotonylation support a function of histone crotonylation in transcription. However, the enzyme(s) responsible for histone decrotonylation (HDCR) remains poorly defined. Moreover, it remains to be determined if histone crotonylation is physiologically significant and functionally distinct from or redundant to histone acetylation. Here we present evidence that class I histone deacetylases (HDACs) rather than sirtuin family deacetylases (SIRTs) are the major histone decrotonylases, and that histone crotonylation is as dynamic as histone acetylation in mammalian cells. Notably, we have generated novel HDAC1 and HDAC3 mutants with impaired HDAC but intact HDCR activity. Using these mutants we demonstrate that selective HDCR in mammalian cells correlates with a broad transcriptional repression and diminished promoter association of crotonylation but not acetylation reader proteins. Furthermore, we show that histone crotonylation is enriched in and required for self-renewal of mouse embryonic stem cells.

Miniaturized ultrafast switchable optical components with an extremely compact size and a high-speed response will be the core of next-generation all-optical devices instead of traditional integrated circuits, which are approaching the bottleneck of Moore’s Law. Metasurfaces have emerged as fascinating subwavelength flat optical components and devices for light focusing and holography applications. However, these devices exhibit a severe limitation due to their natural passive response. Here we introduce an active hybrid metasurface integrated with patterned semiconductor inclusions for all-optical active control of terahertz waves. Ultrafast modulation of polarization states and the beam splitting ratio are experimentally demonstrated on a time scale of 667 ps. This scheme of hybrid metasurfaces could also be extended to the design of various free-space all-optical active devices, such as varifocal planar lenses, switchable vector beam generators, and components for holography in ultrafast imaging, display, and high-fidelity terahertz wireless communication systems.

By transfection of Coxsackievirus B3 (CVB3) individual protease gene into HeLa cells, we demonstrated that 2A(pro) and 3C(pro) induced apoptosis through multiple converging pathways. Firstly, both 2A(pro) and 3C(pro) induced caspase-8-mediated activation of caspase-3 and dramatically reduced cell viability. Secondly, they both activated the intrinsic mitochondria-mediated apoptosis pathway leading to cytochrome c release from mitochondria and activation of caspase-9. However, 3C(pro) induced these events via both up-regulation of Bax and cleavage of Bid, and 2A(pro) induced these events via cleavage of Bid only. Nevertheless, neither altered Bcl-2 expression. Thirdly, both proteases induced cell death through cleavage or down regulation of cellular factors for translation and transcription: both 2A(pro) and 3C(pro) cleaved eukaryotic translation initiation factor 4GI but their cleavage products are different, indicating different cleavage sites; further, both 2A(pro) and 3C(pro) down-regulated cyclic AMP responsive element binding protein, a transcription factor, with 2A(pro) exhibiting a stronger effect than 3C(pro). Surprisingly, neither could cleave DAP5/p97/NAT1, a translation regulator, although this cleavage was observed during CVB3 infection and could not be blocked by caspase inhibitor z-VAD-fmk. Taken together, these data suggest that 2A(pro) and 3C(pro) induce apoptosis through both activation of proapoptotic mediators and suppression of translation and transcription.

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The present study was conducted to evaluate the effect of the dietary supplementation of Bacillus amyloliquefaciens-based direct-fed microbial (DFM) on growth performance, nutrient utilization, intestinal morphology and cecal microflora in broiler chickens. A total of two hundred and eighty eight 1-d-old Arbor Acres male broilers were randomly allocated to one of four experimental treatments in a completely randomized design. Each treatment was fed to eight replicate cages, with nine birds per cage. Dietary treatments were composed of an antibiotic-free basal diet (control), and the basal diet supplemented with either 15 mg/kg of virginiamycin as antibiotic growth promoter (AGP), 30 mg/kg of Bacillus amyloliquefaciens-based DFM (DFM 30) or 60 mg/kg of Bacillus amyloliquefaciens-based DFM (DFM 60). Experimental diets were fed in two phases: starter (d 1 to 21) and finisher (d 22 to 42). Growth performance, nutrient utilization, morphological parameters of the small intestine and cecal microbial populations were measured at the end of the starter (d 21) and finisher (d 42) phases. During the starter phase, DFM and virginiamycin supplementation improved the feed conversion ratio (FCR; p<0.01) compared with the control group. For the finisher phase and the overall experiment (d 1 to 42) broilers fed diets with the DFM had better body weight gain (BWG) and FCR than that of control (p<0.05). Supplementation of virginiamycin and DFM significantly increased the total tract apparent digestibility of crude protein (CP), dry matter (DM) and gross energy during both starter and finisher phases (p<0.05) compared with the control group. On d 21, villus height, crypt depth and villus height to crypt depth ratio of duodenum, jejunum, and ileum were significantly increased for the birds fed with the DFM diets as compared with the control group (p<0.05). The DFM 30, DFM 60, and AGP groups decreased the Escherichia coli population in cecum at d 21 and d 42 compared with control group (p<0.01). In addition, the population of Lactobacillus was increased in DFM 30 and DFM 60 groups as compared with control and AGP groups (p<0.01). It can be concluded that Bacillus amyloliquefaciens-based DFM could be an alternative to the use of AGPs in broilers diets based on plant protein.

2The purpose of this 2-year multicentric, randomized, placebo-controlled study was to evaluate the long-term effects and adverse effects of spironolactone on chronic dialysis patients. A total of 253 non-heart failure dialysis patients with end-stage renal disease were randomly assigned to 2-year treatment with spironolactone (25 mg once daily, n=125) or a matching placebo (n=128) as add-on therapy. The primary outcome was a composite of death from cardiocerebrovascular (CCV) events, aborted cardiac arrest, and sudden cardiac death, and the secondary outcome was death from all causes. Other CCV-related indexes such as left ventricular mass index, left ventricular ejection fraction, heart rate variability, vascular endothelial function, and blood pressure-lowering effect were analyzed for patients who completed the whole 2-year follow-up study. Sociodemographic, clinical, and relevant laboratory data were also collected. During the 2-year follow-up, the primary outcome occurred less frequently in the spironolactone group vs the control group (7.2% vs 18.0%; adjusted hazard ratio [HR], 0.42; 95% confidence interval [CI], 0. 26-0.78). Death from CCV events occurred in 4.0% of patients in the spironolactone group and in 11.7% of patients in the control group. Neither aborted cardiac arrest nor sudden cardiac death was significantly reduced by spironolactone treatment. The secondary outcome occurred less frequently in the spironolactone group vs the control group (9.6% vs 19.5%; adjusted HR, 0.52; 95% CI, 0.29-0.94). Other CCV-related indexes except for heart rate variability were significantly improved. This study demonstrates that use of low-dose spironolactone in non-heart failure dialysis patients can effectively reduce the risks of both CCV morbidity and mortality with few side effects. Moreover, the beneficial effect was mediated through improving the endothelial function or reducing left ventricular size independent of blood pressure changes, rather than mediation through changes in salt or potassium handling in the kidney. J Clin Hypertens (Greenwich). 2016;18:121-128. ª2015 Wiley Periodicals, Inc.End-stage renal disease (ESRD) is recognized as a rapidly-growing global health burden. At present, there are two effective renal replacement methods for treatment of ESRD, including chronic dialysis and renal transplant. Growing evidence suggests that patients with chronic kidney disease or dialysis have higher risks and severity of cardiocerebrovascular (CCV) diseases compared with the general population.1-3 One reason is attributed to several traditional and nontraditional risk factors and even uremia-or dialysis-related factors. Farraginous factors will cause ill-defined pathophysiologic processes (eg, persistent inflammation, endothelial dysfunction, oxidative stress, autonomic dysfunction, and vascular calcification) that are associated with the development of uremic cardiomyopathy or uremic vascular disease.4 CCV diseases account for more than 50% of deaths among dialysis patients with ESRD. Thus, management ...

Understanding how the dynamics of vegetation growth respond to climate change at different temporal and spatial scales is critical to projecting future ecosystem dynamics and the adaptation of ecosystems to global change. In this study, we investigated vegetated growth dynamics (annual productivity, seasonality and the minimum amount of vegetated cover) in China and their relations with climatic factors during 1982-2011, using the updated Global Inventory Modeling and Mapping Studies (GIMMS) third generation global satellite Advanced Very High Resolution Radiometer (AVHRR) Normalized Difference Vegetation Index (NDVI) dataset and climate data acquired from the National (1) annual mean NDVI over China significantly increased by about 0.0006 per year from 1982 to 2011; (2) of the vegetated area in China, over 33% experienced a significant positive trend in vegetation growth, mostly located in central and southern China; about 21% experienced a significant positive trend in growth seasonality, most of which occurred in northern China (>35°N); (3) changes in vegetation growth dynamics were significantly correlated with air temperature and precipitation (p < 0.001) at a region scale; (4) at the country scale, changes in NDVI was significantly and positively correlated with annual air temperature (r = 0.52, p < 0.01) and not associated with annual precipitation (p > 0.1); (5) of the vegetated area, about 24% showed significant correlations between annual mean NDVI and air temperature (93% positive and remainder negative), and 12% showed significant correlations of annual mean NDVI with annual precipitation (65% positive and 35% negative). The spatiotemporal variations in vegetation growth dynamics were controlled primarily by temperature and secondly by precipitation. Vegetation growth was also affected by human activities; and (6) monthly NDVI was significantly correlated with the preceding month's temperature and precipitation in western, central and northern China. The effects of a climate lag of more than two months in southern China may be caused mainly by the abundance of precipitation. These findings suggest that continuing efforts to monitor vegetation changes (in situ and satellite observations) over time and at broad scales are greatly needed, and are critical for the management of ecosystems and adapting to global climatic changes. It is likewise difficult to predict well future vegetation growth without linking these observations to mechanistic terrestrial ecosystem processes models that integrate all the satellite and in situ observations.

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