No abstract

Background-Exacerbations of childhood asthma and rhinovirus infections both peak during the spring and fall, suggesting that viral infections are major contributors to seasonal asthma morbidity.

SUMMARY Directed reprogramming of human fibroblasts into fully-differentiated neurons requires massive changes in epigenetic and transcriptional states. Induction of a chromatin environment permissive to acquiring neuronal subtype identity is therefore a major barrier to fate conversion. Here we show that the brain-enriched miRNAs miR-9/9* and miR-124 (miR-9/9*-124) trigger reconfiguration of chromatin accessibility, DNA methylation, and mRNA expression to induce a default neuronal state. MiR-9/9*-124-induced neurons (miNs) are functionally excitable and are uncommitted towards specific subtypes yet possess open chromatin at neuronal subtype-specific loci, suggesting such identity can be imparted by additional lineage-specific transcription factors. Consistently, we show ISL1 and LHX3 selectively drive conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, this study shows modular synergism between miRNAs and neuronal subtype-specific transcription factors can drive lineage-specific neuronal reprogramming, thereby providing a general platform for high-efficiency generation of distinct subtypes of human neurons.

The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator.

This study suggests that humidifier disinfectant inhalation causes an idiopathic type of chILD that is characterized by spontaneous air leak, rapid progression, lack of response to treatment, and high mortality. Further safety studies must be performed on common environmental compounds, particularly those that enter the human body by an unusual route.

No abstract

No abstract

This study aimed to investigate the association between a dual-task intervention program and cognitive and physical functions. In a randomized controlled trial, we enrolled 49 individuals with MCI. The MCI diagnosis was based on medical evaluations through a clinical interview conducted by a dementia specialist. Cognitive assessments were performed by neuropsychologists according to standardized methods, including the MMSE and modified Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-Cog), both at baseline and at 3 months follow-up. The program comprised physical activity and behavior modification, aerobic exercise, and a cognitive and exercise combined intervention program. Analysis of the subjects for group-time interactions revealed that the exercise group exhibited a significantly improved ADAS-Cog, working memory, and executive function. Total physical activity levels were associated with improvements in working memory function and the modified ADAS-Cog score, and the associations were stronger for daily moderate intensity activity than for daily step count. The 24-week combined intervention improved cognitive function and physical function in patients with MCI relative to controls. Encouraging participants to perform an additional 10 min of moderate physical activity under supervision, during ongoing intervention, may be more beneficial to prevent cognitive decline and improve exercise adherence.