Twigraph: Discovering and Visualizing Influential Words between Twitter Profiles

The social media craze is on an ever increasing spree, and people are connected with each other like never before, but these vast connections are visually unexplored. We propose a methodology Twigraph to explore the connections between persons using their Twitter profiles. First, we propose a hybrid approach of recommending social media profiles, articles, and advertisements to a user.The profiles are recommended based on the similarity score between the user profile, and profile under evaluation. The similarity between a set of profiles is investigated by finding the top influential words thus causing a high similarity through an Influence Term Metric for each word. Then, we group profiles of various domains such as politics, sports, and entertainment based on the similarity score through a novel clustering algorithm. The connectivity between profiles is envisaged using word graphs that help in finding the words that connect a set of profiles and the profiles that are connected to a word. Finally, we analyze the top influential words over a set of profiles through clustering by finding the similarity of that profiles enabling to break down a Twitter profile with a lot of followers to fine level word connections using word graphs. The proposed method was implemented on datasets comprising 1.1 M Tweets obtained from Twitter. Experimental results show that the resultant influential words were highly representative of the relationship between two profiles or a set of profile

RNAi Codex: a portal/database for short-hairpin RNA (shRNA) gene-silencing constructs

Use of RNA interference (RNAi) in forward genetic screens is proliferating. Currently, short-interfering RNAs (siRNAs) and short-hairpin RNAs (shRNAs) are being used to silence genes to tease out functional information. It is becoming easier to harness RNAi to silence specific genes, owing to the development of libraries of readymade shRNA and siRNA gene-silencing constructs by using a variety of sources. RNAi Codex, which consists of a database of shRNA related information and an associated website, has been developed as a portal for publicly available shRNA resources and is accessible at . RNAi Codex currently holds data from the Hannon–Elledge shRNA library and allows the use of biologist-friendly gene names to access information on shRNA constructs that can silence the gene of interest. It is designed to hold user-contributed annotations and publications for each construct, as and when such data become available. We will describe features of RNAi Codex and explain the use of the tool

Processing of Drosophila endo-siRNAs depends on a specific Loquacious isoform

Drosophila melanogaster expresses three classes of small RNAs, which are classified according to their mechanisms of biogenesis. MicroRNAs are ∼22-23 nucleotides (nt), ubiquitously expressed small RNAs that are sequentially processed from hairpin-like precursors by Drosha/Pasha and Dcr-1/Loquacious complexes. MicroRNAs usually associate with AGO1 and regulate the expression of protein-coding genes. Piwi-interacting RNAs (piRNAs) of ∼24-28 nt associate with Piwi-family proteins and can arise from single-stranded precursors. piRNAs function in transposon silencing and are mainly restricted to gonadal tissues. Endo-siRNAs are found in both germline and somatic tissues. These ∼21-nt RNAs are produced by a distinct Dicer, Dcr-2, and do not depend on Drosha/Pasha complexes. They predominantly bind to AGO2 and target both mobile elements and protein-coding genes. Surprisingly, a subset of endo-siRNAs strongly depend for their production on the dsRNA-binding protein Loquacious (Loqs), thought generally to be a partner for Dcr-1 and a cofactor for miRNA biogenesis. Endo-siRNA production depends on a specific Loqs isoform, Loqs-PD, which is distinct from the one, Loqs-PB, required for the production of microRNAs. Paralleling their roles in the biogenesis of distinct small RNA classes, Loqs-PD and Loqs-PB bind to different Dicer proteins, with Dcr-1/Loqs-PB complexes and Dcr-2/Loqs-PD complexes driving microRNA and endo-siRNA biogenesis, respectively. Copyright © 2009 RNA Society

miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex

Neurogenesis during the development of the mammalian cerebral cortex involves a switch of neural stem and progenitor cells from proliferation to differentiation. To explore the possible role of microRNAs (miRNAs) in this process, we conditionally ablated Dicer in the developing mouse neocortex using Emx1-Cre, which is specifically expressed in the dorsal telencephalon as early as embryonic day (E) 9.5. Dicer ablation in neuroepithelial cells, which are the primary neural stem and progenitor cells, and in the neurons derived from them, was evident from E10.5 onwards, as ascertained by the depletion of the normally abundant miRNAs miR-9 and miR-124. Dicer ablation resulted in massive hypotrophy of the postnatal cortex and death of the mice shortly after weaning. Analysis of the cytoarchitecture of the Dicer-ablated cortex revealed a marked reduction in radial thickness starting at E13.5, and defective cortical layering postnatally. Whereas the former was due to neuronal apoptosis starting at E12.5, which was the earliest detectable phenotype, the latter reflected dramatic impairment of neuronal differentiation. Remarkably, the primary target cells of Dicer ablation, the neuroepithelial cells, and the neurogenic progenitors derived from them, were unaffected by miRNA depletion with regard to cell cycle progression, cell division, differentiation and viability during the early stage of neurogenesis, and only underwent apoptosis starting at E14.5. Our results support the emerging concept that progenitors are less dependent on miRNAs than their differentiated progeny, and raise interesting perspectives as to the expansion of somatic stem cells

Discovery of progenitor cell signatures by time-series synexpression analysis during Drosophila embryonic cell immortalization

The use of time series profiling to identify groups of functionally related genes (synexpression groups) is a powerful approach for the discovery of gene function. Here we apply this strategy during RasV12 immortalization of Drosophila embryonic cells, a phenomenon not well characterized. Using high-resolution transcriptional time-series datasets, we generated a gene network based on temporal expression profile similarities. This analysis revealed that common immortalized cells are related to adult muscle precursors (AMPs), a stem cell-like population contributing to adult muscles and sharing properties with vertebrate satellite cells. Remarkably, the immortalized cells retained the capacity for myogenic differentiation when treated with the steroid hormone ecdysone. Further, we validated in vivo the transcription factor CG9650, the ortholog of mammalian Bcl11a/b, as a regulator of AMP proliferation predicted by our analysis. Our study demonstrates the power of time series synexpression analysis to characterize Drosophila embryonic progenitor lines and identify stem/progenitor cell regulators

Resonant X-Ray Scattering on the M-Edge Spectra from Triple-k Structure Phase in U_{0.75}Np_{0.25}O_{2} and UO_{2}

We derive an expression for the scattering amplitude of resonant x-ray scattering under the assumption that the Hamiltonian describing the intermediate state preserves spherical symmetry. On the basis of this expression, we demonstrate that the energy profile of the RXS spectra expected near U and Np M_4 edges from the triple-k antiferromagnetic ordering phase in UO_{2} and U_{0.75}Np_{0.25}O_{2} agree well with those from the experiments. We demonstrate that the spectra in the \sigma-\sigma' and \sigma-\pi' channels exhibit quadrupole and dipole natures, respectively.Comment: 3 pages, 3 figures, to be published in J. Phys. Soc. Jpn. Supp

Clozapine-induced transcriptional changes in the zebrafish brain

Clozapine is an atypical antipsychotic medication that is used to treat schizophrenia patients who are resistant to other antipsychotic drugs. The molecular mechanisms mediating the effects of clozapine are not well understood and its use is often associated with severe side-effects. In this study, we exposed groups of wild-type zebrafish to two doses of clozapine ('low' (20 µg/L) and 'high' (70 µg/L)) over a 72-h period, observing dose-dependent effects on behaviour. Using RNA sequencing (RNA-seq) we identified multiple genes differentially expressed in the zebrafish brain following exposure to clozapine. Network analysis identified co-expression modules characterised by striking changes in module connectivity in response to clozapine, and these were enriched for regulatory pathways relevant to the etiology of schizophrenia. Our study highlights the utility of zebrafish as a model for assessing the molecular consequences of antipsychotic medications and identifies genomic networks potentially involved in schizophrenia.This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site.This work was supported by a Medical Research Council (MRC) Project Grant (MR/K013807/1) and Clinical Infrastructure Funding (MR/M008924/1) to JM. JV is funded by an RCUK/UKRI Rutherford Fund Fellowship (MR/R024987/1). We would like to acknowledge the use of the University of Exeter High-Performance Computing (HPC) facility in carrying out this work.published version, accepted version, submitted versio

Obstructive sleep apnoea in obese adolescents and cardiometabolic risk markers

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: In paediatric patients, obstructive sleep apnoea is associated with adiposity, especially visceral adiposity. In adults, obstructive sleep apnoea is also associated with a higher prevalence of cardiovascular disease and type 2 diabetes. There are limited and conflicting paediatric studies examining the association between obstructive sleep apnoea and biomarkers of risk for cardiovascular disease and type 2 diabetes in youth. WHAT THIS STUDY ADDS: Obstructive sleep apnoea is linked with greater cardiometabolic risk markers in obese adolescents. Fasting insulin and homeostasis model assessment-insulin resistance may be especially linked with obstructive sleep apnoea among obese male Hispanic adolescents. The relationship between obstructive sleep apnoea and cardiometabolic abnormalities in obese adolescents should be considered when evaluating patients found to have obstructive sleep apnoea. BACKGROUND: Paediatric studies examining the association between obstructive sleep apnoea (OSA) and insulin sensitivity/cardiometabolic risk are limited and conflicting. OBJECTIVE: This study aims to determine if cardiometabolic risk markers are increased among obese youth with obstructive sleep apnoea as compared with their equally obese peers without OSA. METHODS: We performed a retrospective analysis of 96 patients (age 14.2 ± 1.4 years) who underwent polysomnography for suspected OSA. Fasting lipids, glucose, insulin and haemoglobin A1 c (HbA1 c) were performed as part of routine clinical evaluation. Patients were categorized into two groups by degree of OSA as measured by the apnoea-hypopnoea index (AHI): none or mild OSA (AHI < 5) and moderate or severe OSA (AHI ≥ 5). RESULTS: Despite the similar degrees of obesity, patients with moderate or severe OSA had higher fasting insulin (P = 0.037) and homeostasis model assessment-insulin resistance (HOMA-IR [P = 0.0497]) as compared with those with mild or no OSA. After controlling for body mass index, there was a positive association between the AHI and log HOMA-IR (P = 0.005). There was a positive relationship between arousals plus awakenings during the polysomnography and fasting triglycerides. CONCLUSIONS: OSA is linked with greater cardiometabolic risk markers in obese youth