Neurotoxicological effects induced by up-regulation of miR-137 following triclosan exposure to zebrafish (Danio rerio).

Triclosan (TCS) is a prevalent anthropogenic contaminant in aquatic environments and its chronic exposure can lead to a series of neurotoxic effects in zebrafish. Both qRT-PCR and W-ISH identified that TCS exposure resulted in significant up-regulation of miR-137, but downregulation of its regulatory genes (bcl11aa, MAPK6 and Runx1). These target genes are mainly associated with neurodevelopment and the MAPK signaling pathway, and showed especially high expression in the brain. After overexpression or knockdown treatments by manual intervention of miR-137, a series of abnormalities were induced, such as ventricular abnormality, bent spine, yolk cyst, closure of swim sac and venous sinus hemorrhage. The most sensitive larval toxicological endpoint from intervened miR-137 expression was impairment of the central nervous system (CNS), ventricular abnormalities and notochord curvature. Microinjection of microRNA mimics or inhibitors of miR-137 both caused zebrafish malformations. The posterior lateral line neuromasts became obscured and decreased in number in intervened miR-137 groups and TCS-exposure groups. Up-regulation of miR-137 led to more severe neurotoxic effects than its down-regulation. Behavioral observations demonstrated that both TCS exposure and miR-137 over-expression led to inhibited hearing or vision sensitivity. HE staining indicated that hearing and vision abnormalities induced by long-term TCS exposure originated from CNS injury, such as reduced glial cells and loose and hollow fiber structures. The findings of this study enhance our mechanistic understanding of neurotoxicity in aquatic animals in response to TCS exposure. These observations provide theoretical guidance for development of early intervention treatments for nervous system diseases

Updating the DCC Curation Lifecycle Model

The DCC Curation Lifecycle Model has played a vital role in the field of data curation for over a decade. During that time, the scale and complexity of data have changed dramatically, along with the contexts of data production and use. This paper reports on a study examining factors impacting data curation practices and presents recommendations for updating the DCC Curation Lifecycle Model. The study was grounded in a review of other lifecycle models and informed by a site visit to the Digital Curation Centre and consultation with expert practitioners and researchers. Framed by contemporary conditions impacting the conduct of research and provision of data services, the analysis and proposed recommendations account for the prominence of machine-actionable data, the importance of machine learning for data processing and analytics, growth of integrated research workflows, and escalating concerns with fairness, accountability, and transparency of data and algorithms

PSR J1926-0652: A Pulsar with Interesting Emission Properties Discovered at FAST

We describe PSR J1926-0652, a pulsar recently discovered with the Five-hundred-meter Aperture Spherical radio Telescope (FAST). Using sensitive single-pulse detections from FAST and long-term timing observations from the Parkes 64-m radio telescope, we probed phenomena on both long and short time scales. The FAST observations covered a wide frequency range from 270 to 800 MHz, enabling individual pulses to be studied in detail. The pulsar exhibits at least four profile components, short-term nulling lasting from 4 to 450 pulses, complex subpulse drifting behaviours and intermittency on scales of tens of minutes. While the average band spacing P3 is relatively constant across different bursts and components, significant variations in the separation of adjacent bands are seen, especially near the beginning and end of a burst. Band shapes and slopes are quite variable, especially for the trailing components and for the shorter bursts. We show that for each burst the last detectable pulse prior to emission ceasing has different properties compared to other pulses. These complexities pose challenges for the classic carousel-type models.Comment: 13pages with 12 figure

Efficacy of EGFR-TKI therapy in patients with brain metastases from non-small-cell lung cancer: A metaanalysis

Purpose: This meta-analysis aimed to systematically evaluate the efficacy of tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) for patients with brain metastases (BM) from nonsmall- cell lung cancer (NSCLC), and to compare this treatment modality to chemotherapy or radiotherapy.Methods: PubMed, EMBASE (OvidSP), the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and ASCO Annual Meeting Abstracts were searched. Controlled clinical studies that compared the efficacy of EGFR-TKIs with chemotherapy or radiotherapy for NSCLC patients with BM were included in the analysis. Efficacy indicators included overall survival (OS), local progression-free survival (LPFS) and objective response rate (ORR).Results: The final sample consisted of 24,637 NSCLC patients with BM from 11 clinical studies. In primary efficacy analysis, it was found that EGFR-TKIs were significantly superior to chemotherapy or radiotherapy in terms of ORR (odds ratio (OR) = 2.10, p = 0.035), OS (hazard ratio (HR) = 0.78, p = 0.011) and LPFS (HR = 0.60, p < 0.001).Conclusion: Among the patients with BM from NSCLC, EGFR-TKIs exhibit a therapeutic advantage over chemotherapy or radiotherapy, which is reflected in the elevation of ORR and improvement in OS and LPFS.Keywords: Brain metastasis, Non-small-cell lung cancer (NSCLC), Protein kinase Inhibitors, Epidermal growth factor, Meta-analysi

Aging impacts isolated lymphoid follicle development and function

<p>Abstract</p> <p>Background</p> <p>Immunosenescence is the age-related decline and dysfunction of protective immunity leading to a marked increase in the risk of infections, autoimmune disease, and cancer. The majority of studies have focused on immunosenescence in the systemic immune system; information concerning the effect of aging on intestinal immunity is limited. Isolated lymphoid follicles (ILFs) are newly appreciated dynamic intestinal lymphoid structures that arise from nascent lymphoid tissues, or cryptopatches (CP), in response to local inflammatory stimuli. ILFs promote "homeostatic" responses including the production of antigen-specific IgA, thus playing a key role in mucosal immune protection. ILF dysfunction with aging could contribute to immunosenescence of the mucosal system, and accordingly we examined phenotypic and functional aspects of ILFs from young (2 month old) and aged (2 year old) mice.</p> <p>Results</p> <p>We observed that aged mice have increased numbers of ILFs and increased numbers of structures corresponding to an early stage of CPs transforming into ILFs. The cellular composition of ILFs in aged mice is altered with a smaller B-lymphocyte population and an increased T-lymphocyte population. The ILF T-lymphocyte population is notable by the presence of CD4+ CD8αα+ T-lymphocytes, which are absent from the systemic compartment. The smaller B-lymphocyte population in ILFs from aged mice is directly correlated with decreased mRNA and protein expression of CCL20 and CXCL13, two chemokines that play crucial roles in recruiting B-lymphocytes into ILFs. Aged mice had elevated levels of serum and fecal immunoglobulins and despite the decreased B-lymphocyte population, ILFs from aged mice displayed increased IgA production. The immunoglobulin repertoire was skewed in aged mice, and ILFs demonstrated a repertoire usage similar to that of the systemic pool in both young and aged mice.</p> <p>Conclusions</p> <p>Here we observed that ILF development, cellular composition, and immunoglobulin production are altered with aging suggesting that ILF dysfunction contributes to mucosal immunosenescence.</p

Glucagon-like peptide-1 and its class B G protein-coupled receptors: A long march to therapeutic successes

Theglucagon-likepeptide (GLP)-1receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secretedfromthreemajor tissues inhumans,enteroendocrine L cells in the distal intestine, a cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity. Physiologic and biochemical studies with truncated, chimeric, and mutated peptides and GLP-1R variants, together with ligand-bound crystal structures of the extracellular domain and the first three-dimensional structures of the 7-helical transmembrane domain of class B GPCRs, have provided the basis for a twodomain-binding mechanism of GLP-1 with its cognate receptor. Although efforts in discovering therapeutically viable nonpeptidicGLP-1R agonists have been hampered, small-moleculemodulators offer complementary chemical tools to peptide analogs to investigate ligand-directed biased cellular signaling of GLP-1R. The integrated pharmacological and structural information of different GLP-1 analogs and homologous receptors give new insights into the molecular determinants of GLP-1R ligand selectivity and functional activity, thereby providing novel opportunities in the design and development of more efficacious agents to treat metabolic disorders

Integrity Evaluation of Customs Cooperation Based on Gray and Fuzzy Decision Theory

Abstract. The integrity evaluation of cooperation does well to standardizing enterprise behavior, and constructing of an orderly competitive operating background. Evaluation term and method are most important in evaluation. In this paper, an evaluation system was designed, which included 3-level evaluation terms and a fusing optimized algorithm. During the course, multi-hierarchy analysis was used to design index structure firstly, and then the integrated Gray theory and Genetic algorithm were introduced to optimize index&apos;s weight. The innovation was reflected in article included an evaluation system with customs characteristics, and cooperation&apos;s integrity graded model based on quantitative evaluation