The accumulation of unfolded protein in the endoplasmic reticulum (ER) attenuates protein synthesis initiation through phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha) at Ser51. Subsequently, transcription of genes encoding adaptive functions including the glucose-regulated proteins is induced. We show that eIF2alpha phosphorylation is required for translation attenuation, transcriptional induction, and survival in response to ER stress. Mice with a homozygous mutation at the eIF2alpha phosphorylation site (Ser51Ala) died within 18 hr after birth due to hypoglycemia associated with defective gluconeogenesis. In addition, homozygous mutant embryos and neonates displayed a deficiency in pancreatic beta cells. The results demonstrate that regulation of translation through eIF2alpha phosphorylation is essential for the ER stress response and in vivo glucose homeostasis.
The pig is a major species for livestock production and is also extensively used as the preferred model species for analyses of a wide range of human physiological functions and diseases(1). The importance of the gut microbiota in complementing the physiology and genome of the host is now well recognized(2). Knowledge of the functional interplay between the gut microbiota and host physiology in humans has been advanced by the human gut reference catalogue(3,4). Thus, establishment of a comprehensive pig gut microbiome gene reference catalogue constitutes a logical continuation of the recently published pig genome(5). By deep metagenome sequencing of faecal DNA from 287 pigs, we identified 7.7 million non-redundant genes representing 719 metagenomic species. Of the functional pathways found in the human catalogue, 96% are present in the pig catalogue, supporting the potential use of pigs for biomedical research. We show that sex, age and host genetics are likely to influence the pig gut microbiome. Analysis of the prevalence of antibiotic resistance genes demonstrated the effect of eliminating antibiotics from animal diets and thereby reducing the risk of spreading antibiotic resistance associated with farming systems.
Organic field-effect transistors (OFETs) are promising for numerous potential applications but suffer from poor charge injection, such that their performance is severely limited. Recent efforts in lowering contact resistance have led to significantly improved field-effect mobility of OFETs, up to 100 times higher, as the results of careful choice of contact materials and/or chemical treatment of contact electrodes. Here we review the innovative developments of contact engineering and focus on the mechanisms behind them. Further improvement toward Ohmic contact can be expected along with the rapid advance in material research, which will also benefit other organic and electronic devices.
Simple solvent‐vapor annealing was used to fabricate single crystals of dioctylbenzothienobenzothiophene on a polymer dielectric surface. By involving self‐organized phase separation, crystal length is enhanced and a good semiconductor/insulator interface is obtained. The field‐effect transistors (FETs) exhibit an average p‐type FET mobility of 3.0 cm2 V−1 s−1, with a highest value of 9.1 cm2 V−1 s−1. The FET mobility increases as temperature decreases, which suggests intrinsic bandlike transport.
Hydrogen production through water splitting has been considered as a green, pure and high-efficient technique. As an important half-reaction involved, hydrogen evolution reaction is a complex electrochemical process involving liquid-solid-gas three-phase interface behaviour. Therefore, new concepts and strategies of material design are needed to smooth each pivotal step. Here we report a multiscale structural and electronic control of molybdenum disulfide foam to synergistically promote the hydrogen evolution process. The optimized three-dimensional molybdenum disulfide foam with uniform mesopores, vertically aligned two-dimensional layers and cobalt atoms doping demonstrated a high hydrogen evolution activity and stability. In addition, density functional theory calculations indicate that molybdenum disulfide with moderate cobalt doping content possesses the optimal activity. This study demonstrates the validity of multiscale control in molybdenum disulfide via overall consideration of the mass transport, and the accessibility, quantity and capability of active sites towards electrocatalytic hydrogen evolution, which may also be extended to other energy-related processes.
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