Tasks representing 9 cognitive constructs of potential importance to understanding Chinese reading development and impairment were administered to 75 children with dyslexia and 77 age-matched children without reading difficulties in 5th and 6th grade. Logistic regression analyses revealed that dyslexic readers were best distinguished from age-matched controls with tasks of morphological awareness, speeded number naming, and vocabulary skill; performance on tasks of visual skills or phonological awareness failed to distinguish the groups. Path analyses further revealed that a construct of morphological awareness was the strongest consistent predictor of a variety of literacy-related skills across both groups. Findings suggest that morphological awareness may be a core theoretical construct necessary for explaining variability in reading Chinese.

Perturbation of endoplasmic reticulum (ER) homeostasis impairs insulin biosynthesis, beta cell survival, and glucose homeostasis. We show that a murine model of diabetes is associated with the development of ER stress in beta cells and that treatment with the GLP-1R agonist exendin-4 significantly reduced biochemical markers of islet ER stress in vivo. Exendin-4 attenuated translational downregulation of insulin and improved cell survival in purified rat beta cells and in INS-1 cells following induction of ER stress in vitro. GLP-1R agonists significantly potentiated the induction of ATF-4 by ER stress and accelerated recovery from ER stress-mediated translational repression in INS-1 beta cells in a PKA-dependent manner. The effects of exendin-4 on the induction of ATF-4 were mediated via enhancement of ER stress-stimulated ATF-4 translation. Moreover, exendin-4 reduced ER stress-associated beta cell death in a PKA-dependent manner. These findings demonstrate that GLP-1R signaling directly modulates the ER stress response leading to promotion of beta cell adaptation and survival.

Ultrasmall molybdenum sulfide nanoparticles with diameters of 1.47 AE 0.16 nm were fabricated from bulk MoS 2 by a combination of ultrasonication and centrifugation. The nanoparticles were then assembled on an Au surface to form a film with high electrocatalytic activity for hydrogen evolution reaction (HER). A Tafel slope of 69 mV per decade was measured for this film and the onset potential was estimated to be À0.09 V. The small loading (1.03 mg cm À2 ) and the high current density (0.92 mA cm À2 at h ¼ 0.15 V) demonstrated extremely high catalytic efficiency. X-ray photoelectron spectroscopic results revealed that the assembled nanoparticle film was sulfur enriched with abundant S edges and a structural rearrangement of the S rich particles might occur during the self-assembly process, resulting in significantly enhanced electrocatalytic activity for HER. Electrochemical impedance measurements suggested that the assembling process optimized the conductivity of the nanoparticle film, which contributed to the enhanced HER catalytic activity. Our research has provided a new way to synthesize active molybdenum sulfide nanoparticles for HER and a new approach to achieve enrichment of S edges on molybdenum sulfide, which might have potential use not only for electrocatalytic HER, but also for photoelectrocatalytic HER and plasmon-enhanced water splitting. Broader contextHydrogen produced by the water splitting process could potentially address the needs for the sustainable production of fuels in a manner that is renewable and carbon-free. However, cheap catalysts are required to overcome the large overpotential for hydrogen evolution reaction (HER) in an affordable manner. Recent studies have shown that sulfur edges of MoS 2 are quite active for HER. As a result, much effort has been focused on trying to acquire MoS 2 or MoS x nanomaterials with a plethora of sulfur edges. Here, we demonstrate a novel approach for synthesizing monodispersed molybdenum sulde nanoparticles with ultrasmall diameters and a new strategy for achieving enrichment of active S edges on molybdenum suldes by exploiting the covalent bonding of the nanocatalysts with the underlying gold electrode. The work is benecial not only for the design of highly efficient molybdenum sulde based HER catalysts but also for the synthesis of new catalysts for photoelectrocatalytic HER and plasmon-enhanced water splitting.

No abstract

Tasks tapping visual skills, orthographic knowledge, phonological awareness, speeded naming, morphological awareness and Chinese character recognition were administered to 184 kindergarteners and 273 primary school students from Beijing. Regression analyses indicated that only syllable deletion, morphological construction and speeded number naming were unique correlates of Chinese character recognition in kindergarteners. Among primary school children, the independent correlates of character recognition were rime detection, homophone judgement, morpheme production, orthographic knowledge and speeded number naming. Results underscore the importance of some dimensions of both phonological processing and morphological awareness for both very early and intermediate Chinese reading acquisition. Although significantly correlated with character recognition in younger (but not older) children, visual skills were not uniquely associated with Chinese character reading at any grade level. However, orthographic skills were strongly associated with reading in primary school but not kindergarten, suggesting that orthographic skills are more important for literacy development as reading experience increases.

The function of cyclin G, a commonly induced p53 target, has remained elusive. We show that cyclin G forms a quaternary complex in vivo and in vitro with enzymatically active phosphatase 2A (PP2A) holoenzymes containing B' subunits. Interestingly, cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells. Cyclin G expression also results in reduced phosphorylation of human Hdm2 at S166. Thus, our data suggest that cyclin G recruits PP2A in order to modulate the phosphorylation of Mdm2 and thereby to regulate both Mdm2 and p53.

BackgroundThe greatest genetic risk factor for late-onset Alzheimer's disease (AD) is the ϵ4 allele of Apolipoprotein E (ApoE). ApoE regulates secretion of the potent neuroprotective signaling lipid Sphingosine 1-phosphate (S1P). S1P is derived by phosphorylation of sphingosine, catalysed by sphingosine kinases 1 and 2 (SphK1 and 2), and SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons. S1P and its receptor family have been subject to intense pharmacological interest in recent years, following approval of the immunomodulatory drug Fingolimod, an S1P mimetic, for relapsing multiple sclerosis.ResultsWe quantified S1P levels in six brain regions that are differentially affected by AD pathology, in a cohort of 34 post-mortem brains, divided into four groups based on Braak neurofibrillary tangle staging. S1P declined with increasing Braak stage, and this was most pronounced in brain regions most heavily affected by AD pathology. The S1P/sphingosine ratio was 66% and 64% lower in Braak stage III/IV hippocampus (p = 0.010) and inferior temporal cortex (p = 0.014), respectively, compared to controls. In accordance with this change, both SphK1 and SphK2 activity declined with increasing Braak pathology in the hippocampus (p = 0.032 and 0.047, respectively). S1P/sphingosine ratio was 2.5-fold higher in hippocampus of ApoE2 carriers compared to ApoE4 carriers, and multivariate regression showed a significant association between APOE genotype and hippocampal S1P/sphingosine (p = 0.0495), suggesting a new link between APOE genotype and pre-disposition to AD.ConclusionsThis study demonstrates loss of S1P and sphingosine kinase activity early in AD pathogenesis, and prior to AD diagnosis. Our findings establish a rationale for further exploring S1P receptor pharmacology in the context of AD therapy.

The fundamental understanding of the mechanisms regulating milk protein synthesis is limited. This study aimed to elucidate the metabolic mechanisms of milk production affected by forage quality through studying metabolites from four biofluids (rumen fluid, milk, serum, and urine) collected from 16 lactating cows fed alfalfa hay (AH, high-quality, n = 8) and corn stover (CS, low-quality, n = 8) using gas chromatography-time-of-flight/mass spectrometry. The cows fed AH exhibited higher milk yield (P < 0.01), milk protein yield (P = 0.04), and milk efficiency (P < 0.01) than those fed CS. A total of 165, 195, 218, and 156 metabolites were identified in the rumen fluid, milk, serum, and urine, respectively, while 29 metabolites were found in all four biofluids. In addition 55, 8, 28, and 31 metabolites in each biofluid were significantly different (VIP > 1 and P < 0.05) between the AH- and CS-fed animals. These metabolites were involved in glycine, serine, and threonine metabolism; tyrosine metabolism; and phenylalanine metabolism. Further integrated key metabolic pathway analysis showed that the AH-fed cows may have more comprehensive amino acid metabolisms, suggesting that these metabolite-associated pathways may serve as biomarkers for higher milk yield and better milk protein quality.