Background
Exposure to environmental pollutants promotes Th2 cell responses. Aryl hydrocarbon receptor (AhR) activation aggravates allergic responses. Epithelium‐derived thymic stromal lymphopoietin ...(TSLP), interleukin (IL)‐25, and IL‐33 are implicated in the dysregulation of Th2 immune responses in severe allergic asthma.
Methods
Bronchial biopsies of 28 allergic severe asthma and 6 mild asthma subjects from highly polluted areas were analyzed for AhR nuclear translocation (NT), cytokine expression, and gene activation. Cultured primary epithelial cells were stimulated with diesel exhausted particles (DEP) to determine AhR‐mediated IL‐33, Il‐25, and TSLP synthesis and release.
Results
Primary bronchial epithelial cells exposed to DEP showed upregulation of IL‐33, IL‐25, and TSLP. These effects were abolished by knockdown of AhR by siRNA. Increased AhR/ARNT binding to promoters of IL‐33, IL‐25, and TSLP was found using chromatin immunoprecipitation (ChIP) assay. Allergic severe asthma with high AhR NT had higher bronchial gene and protein expression of IL‐33, IL‐25, and TSLP. These patients derived clinical benefit from anti‐IgE treatment.
Conclusion
Aryl hydrocarbon receptor activation by DEP mediates upregulation of IL‐33, IL‐25, and TSLP with Th2 activation, potentially linking environmental pollution and allergic severe asthma.
Environmental diesel exhaust particles (DEP) exposed to airway epithelium ligate cytoplasmic aryl hydrocarbon receptor (AhR), translocate to the nucleus with aryl hydrocarbon receptor nuclear translocator (ARNT), and then transactivate IL‐33, Il‐25, and TSLP gene expression. Patients with high AhR nucleus translocation overexpressed IL‐33, Il‐25, and TSLP cytokines compared to those with low. Patients with high AhR nucleus translocation are more response to anti‐IgE therapy compared to those with low.
The Notch pathway contributes to self-renewal of tumor-initiating cell and inhibition of normal colonic epithelial cell differentiation. Deregulated expression of Notch1 and Jagged1 is observed in ...colorectal cancer. Hairy/enhancer of split (HES) family, the most characterized targets of Notch, involved in the development of many cancers. In this study, we explored the role of Hes1 in the tumorigenesis of colorectal cancer. Knocking down Hes1 induced CRC cell senescence and decreased the invasion ability, whereas over-expression of Hes1 increased STAT3 phosphorylation activity and up-regulated MMP14 protein level. We further explored the expression of Hes1 in human colorectal cancer and found high Hes1 mRNA expression is associated with poor prognosis in CRC patients. These findings suggest that Hes1 regulates the invasion ability through the STAT3-MMP14 pathway in CRC cells and high Hes1 expression is a predictor of poor prognosis of CRC.
Older patients with chronic diseases often take multiple prescription drugs, increasing their risk of adverse health events. However, polypharmacy remains ill-defined.
To investigate the impact of ...number of drugs prescribed on potentially inappropriate medication (PIM) and the associated risk factors in older outpatients with chronic diseases.
Retrospective cross-sectional study.
We retrospectively assessed 780 older patients (mean, 75.5 ± 7.1 years) with long-term (≥ 28 days) prescriptions for chronic diseases at the geriatric clinics of a university hospital from January to June 2012 using the Screening Tool of Older Person's potentially inappropriate Prescriptions (STOPP). Clinical information for each patient was analyzed. Logistic regression and receiver operating characteristic curve (ROC) analyses were performed; number needed to harm (NNH) was also estimated.
According to STOPP criteria, 302 patients (39%) had at least one PIM. Multivariate analysis revealed that PIM risk was associated with the number of medications prescribed (P < 0.001) and the presence of cardiovascular (P < 0.001) or gastrointestinal disease (P = 0.003). The estimated area under the ROC for the number of medications needed to predict PIM risk was 0.680 (P < 0.001) with the optimal cut-off value of five medications. After adjusting covariates, patients prescribed ≥ 5 drugs adjusted odds ratio (OR) = 5.4; adjusted NNH = 4.25; P < 0.001 and those prescribed 4 drugs (adjusted OR = 3.5; adjusted NNH = 6.88; P = 0.003) had significantly higher PIM risk than those prescribed ≤ 2 drugs.
The number of prescribed medications can be an index of PIM risk in older patients with chronic diseases. Clinicians should suspect high PIM risk in older outpatients with ≥ 5 prescriptions.
The Saccharomyces Genome Database (SGD, http://www.yeastgenome.org) is the community resource for the budding yeast Saccharomyces cerevisiae. The SGD project provides the highest-quality manually ...curated information from peer-reviewed literature. The experimental results reported in the literature are extracted and integrated within a well-developed database. These data are combined with quality high-throughput results and provided through Locus Summary pages, a powerful query engine and rich genome browser. The acquisition, integration and retrieval of these data allow SGD to facilitate experimental design and analysis by providing an encyclopedia of the yeast genome, its chromosomal features, their functions and interactions. Public access to these data is provided to researchers and educators via web pages designed for optimal ease of use.
Rice appearance quality, including traits specifying grain dimension and endosperm chalkiness, represents a major problem in many rice-producing areas of the world. In this study, the genetic basis ...of six appearance quality traits of milled rice was dissected into quantitative trait loci (QTL) main effects, and the stability of these QTLs was assessed in a population of 66 chromosome segment substitution lines (CSSLs) across eight environments. The CSSLs showed transgressive segregation for many of the traits, and significant correlations were detected among most of the traits. Twenty-two QTLs were identified on eight chromosomes, and numerous QTLs affecting related traits were mapped in the same regions, probably reflecting pleiotropic effects. Nine QTLs, namely qGL-1,qGL-3, qGW-5,qLWR-3, qLWR-5,qPGWC-8, qPGWC-9, qACE-8, and qDEC-8, were consistently detected across the eight environments. The additive main effect and multiplicative interaction (AMMI) analysis showed that genotype (G) x environment (E) interaction was significant for all six traits, with the first three iPCA terms accounting for over 80% of the G x E variance. Both D(I) values and the iPCA1-iPCA2 biplots showed that the CSSLs harboring the nine QTL alleles were more stable than those carrying any of the additional 13 QTL alleles, thereby confirming their environmental stability and pointing to their appropriateness as targets for marker-assisted selection for high-quality rice varieties.
The Encyclopedia of DNA Elements (ENCODE) consortium aims to identify all functional elements in the human genome including transcripts, transcriptional regulatory regions, along with their chromatin ...states and DNA methylation patterns. The ENCODE project generates data utilizing a variety of techniques that can enrich for regulatory regions, such as chromatin immunoprecipitation (ChIP), micrococcal nuclease (MNase) digestion and DNase I digestion, followed by deeply sequencing the resulting DNA. As part of the ENCODE project, we have developed a Web-accessible repository accessible at http://factorbook.org. In Wiki format, factorbook is a transcription factor (TF)-centric repository of all ENCODE ChIP-seq datasets on TF-binding regions, as well as the rich analysis results of these data. In the first release, factorbook contains 457 ChIP-seq datasets on 119 TFs in a number of human cell lines, the average profiles of histone modifications and nucleosome positioning around the TF-binding regions, sequence motifs enriched in the regions and the distance and orientation preferences between motif sites.
Background Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD ...have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces. Methods Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces. Results In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces. Limitations The small sample size may have affected our ability to detect additional group differences. Conclusion When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.
In recent years, heavy rainfall conditions have caused disasters around the world. To prevent losses by floods, levees have often been constructed in inundation-prone areas. This study performed ...reliability analyses for the Chiuliao First Levee in southern Taiwan. The failure-related parameters were the water level, the scouring depth, and the in situ friction angle. Three major failure mechanisms were considered: the slope sliding failure of the levee and the sliding and overturning failures of the retaining wall. When the variability of the in situ friction angle and the scouring depth are considered for various flood return periods, the variations of the factor of safety for the different failure mechanisms show that the retaining wall sliding and overturning failures are more sensitive to the change of the friction angle. When the flood return period is greater than 2 years, the levee could fail with slope sliding for all values of the water level difference. The results of levee stability analysis considering the variability of different parameters could aid engineers in designing the levee cross sections, especially with potential failure mechanisms in mind.
The signals that determine activation and repression of specific genes in response to appropriate stimuli are one of the most important, but least understood, types of information encoded in genomic ...DNA. The nucleotide sequence patterns, or motifs, preferentially bound by various transcription factors have been collected in databases. However, these motifs appear to be individually too short and degenerate to enable detection of functional enhancer and silencer elements within a large genome. Several groups have proposed that dense clusters of motifs may diagnose regulatory regions more accurately. Cluster-Buster is the third incarnation of our software for finding clusters of pre-specified motifs in DNA sequences. We offer a Cluster-Buster web server at http://zlab.bu.edu/cluster-buster/.
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