bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between V-ATPase B2 and (Pro) renin Receptors in Promoting the progression of Renal Tubulointerstitial Fibrosis
Authors: Liu Yun , Zuo Sujun , Li Xiaoyan , Fan Jinjin , Cao Xueqin , Yu Xueqing , Yang Qiongqiong 
Published: April 2016

AbstractTo investigate the levels of (Pro) renin receptor [(P) RR], α-smooth muscle actin (α-SMA), fibronectin (FN), and vacuolar H+-ATPase (V-ATPase) subunits (B2, E, and c) in rat unilateral ureteral obstruction (UUO) models and rat proximal tubular epithelial cells (NRK-52E) treated with prorenin to elucidate the role of V-ATPase in these processes by activating the (P) RR. UUO significantly upregulated (P) RR, V-ATPase subunits, α-SMA and FN expression in tubulointerstitium or tubular epithelial cells. A marked colocalization of (P) RR and the B2 subunit was also observed. Prorenin treatment upregulated α-SMA, FN, (P) RR, and V-ATPase subunits and activity in NRK52E cell in a dose- and time-dependent manner. The V-ATPase inhibitor bafilomycin A1 partially blocked prorenin-induced (P) RR, FN, and α-SMA expression. Co-immunoprecipitate and immunofluorescence results demonstrated that the V-ATPase B2 subunit bound to the (P) RR, which was upregulated after prorenin stimulation. Either siRNA-mediated (P) RR or B2 subunit knockdown partially reduced V-ATPase activity and attenuated prorenin-induced FN and α-SMA expression. From the data we can assume that activation of (P) RR and V-ATPase may play an important role in tubulointerstitial fibrosis with possible involvement of interaction of V-ATPase B2 subunit and (P)RR.
Role of time delay on intracellular calcium dynamics driven by non-Gaussian noises
Authors: Duan Wei-Long , Zeng Chunhua 
Published: April 2016

AbstractEffect of time delay (τ) on intracellular calcium dynamics with non-Gaussian noises in transmission processes of intracellular Ca2+ is studied by means of second-order stochastic Runge-Kutta type algorithm. By simulating and analyzing time series, normalized autocorrelation function, and characteristic correlation time of cytosolic and calcium store’s Ca2+ concentration, the results exhibit: (i) intracellular calcium dynamics’s time coherence disappears and stability strengthens as τ → 0.1s; (ii) for the case of τ < 0.1s, the normalized autocorrelation functions of cytosolic and calcium store’s Ca2+ concentration show damped motion when τ is very short, but they trend to a level line as τ → 0.1s, and for the case of τ > 0.1s, they show different variation as τ increases, the former changes from underdamped motion to a level line, but the latter changes from damped motion to underdamped motion; and (iii) at the moderate value of time delay, reverse resonance occurs both in cytosol and calcium store.
Substoichiometric inhibition of transthyretin misfolding by immune-targeting sparsely populated misfolding intermediates: a potential diagnostic and therapeutic for TTR amyloidoses
Authors: Galant Natalie J. , Bugyei-Twum Antoinette , Rakhit Rishi , Walsh Patrick , Sharpe Simon , Arslan Pharhad Eli , Westermark Per , Higaki Jeffrey N. , Torres Ronald , Tapia José , Chakrabartty Avijit 
Published: April 2016

AbstractWild-type and mutant transthyretin (TTR) can misfold and deposit in the heart, peripheral nerves, and other sites causing amyloid disease. Pharmacological chaperones, Tafamidis® and diflunisal, inhibit TTR misfolding by stabilizing native tetrameric TTR; however, their minimal effective concentration is in the micromolar range. By immune-targeting sparsely populated TTR misfolding intermediates (i.e. monomers), we achieved fibril inhibition at substoichiometric concentrations. We developed an antibody (misTTR) that targets TTR residues 89–97, an epitope buried in the tetramer but exposed in the monomer. Nanomolar misTTR inhibits fibrillogenesis of misfolded TTR under micromolar concentrations. Pan-specific TTR antibodies do not possess such fibril inhibiting properties. We show that selective targeting of misfolding intermediates is an alternative to native state stabilization and requires substoichiometric concentrations. MisTTR or its derivative may have both diagnostic and therapeutic potential.
Generation of siRNA Nanosheets for Efficient RNA Interference
Authors: Kim Hyejin , Lee Jae Sung , Lee Jong Bum 
Published: April 2016

AbstractAfter the discovery of small interference RNA (siRNA), nanostructured siRNA delivery systems have been introduced to achieve an efficient regulation of the target gene expression. Here we report a new siRNA-generating two dimensional nanostructure in a formation of nanosized sheet. Inspired by tunable mechanical and functional properties of the previously reported RNA membrane, siRNA nanosized sheets (siRNA-NS) with multiple Dicer cleavage sites were prepared. The siRNA-NS has two dimensional structure, providing a large surface area for Dicer to cleave the siRNA-NS for the generation of functional siRNAs. Furthermore, downregulation of the cellular target gene expression was achieved by delivery of siRNA-NS without chemical modification of RNA strands or conjugation to other substances.
Moonlighting transcriptional activation function of a fungal sulfur metabolism enzyme
Authors: Levati Elisabetta , Sartini Sara , Bolchi Angelo , Ottonello Simone , Montanini Barbara 
Published: April 2016

AbstractMoonlighting proteins, including metabolic enzymes acting as transcription factors (TF), are present in a variety of organisms but have not been described in higher fungi so far. In a previous genome-wide analysis of the TF repertoire of the plant-symbiotic fungus Tuber melanosporum, we identified various enzymes, including the sulfur-assimilation enzyme phosphoadenosine-phosphosulfate reductase (PAPS-red), as potential transcriptional activators. A functional analysis performed in the yeast Saccharomyces cerevisiae, now demonstrates that a specific variant of this enzyme, PAPS-red A, localizes to the nucleus and is capable of transcriptional activation. TF moonlighting, which is not present in the other enzyme variant (PAPS-red B) encoded by the T. melanosporum genome, relies on a transplantable C-terminal polypeptide containing an alternating hydrophobic/hydrophilic amino acid motif. A similar moonlighting activity was demonstrated for six additional proteins, suggesting that multitasking is a relatively frequent event. PAPS-red A is sulfur-state-responsive and highly expressed, especially in fruitbodies and likely acts as a recruiter of transcription components involved in S-metabolism gene network activation. PAPS-red B, instead, is expressed at low levels and localizes to a highly methylated and silenced region of the genome, hinting at an evolutionary mechanism based on gene duplication, followed by epigenetic silencing of this non-moonlighting gene variant.
Consequences of point mutations in melanoma-associated antigen 4 (MAGE-A4) protein: Insights from structural and biophysical studies
Authors: Hagiwara Yoshio , Sieverling Lina , Hanif Farina , Anton Jensy , Dickinson Eleanor R. , Bui Tam T. T. , Andreeva Antonina , Barran Perdita E. , Cota Ernesto , Nikolova Penka V. 
Published: April 2016

AbstractThe Melanoma-Associated Antigen A4 (MAGE-A4) protein is a target for cancer therapy. The function of this protein is not well understood. We report the first comprehensive study on key cancer-associated MAGE-A4 mutations and provide analysis on the consequences of these mutations on the structure, folding and stability of the protein. Based on Nuclear Magnetic Resonance and Circular Dichroism, these mutations had no significant effects on the structure and the folding of the protein. Some mutations affected the thermal stability of the protein remarkably. Native mass spectrometry of wild-type MAGE-A4 showed a broad charge state distribution suggestive of a structurally dynamic protein. Significant intensity was found in relatively low charge states, indicative of a predominantly globular form and some population in more extended states. The latter is supported by Ion Mobility measurements. The MAGE-A4 mutants exhibited similar features. These novel molecular insights shed further light on better understanding of these proteins, which are implicated in a wide range of human cancers.
Identification of a Potential Regulatory Variant for Colorectal Cancer Risk Mapping to 3p21.31 in Chinese Population
Authors: Ke Juntao , Lou Jiao , Zhong Rong , Chen Xueqin , Li Jiaoyuan , Liu Cheng , Gong Yajie , Yang Yang , Zhu Ying , Zhang Yi , Chang Jiang , Gong Jing 
Published: April 2016

AbstractGenome-wide association studies (GWAS) have established chromosome 3p21.31 as a susceptibility locus for colorectal cancer (CRC) that lacks replication and exploration in the Chinese population. We searched potentially functional single nucleotide polymorphisms (SNPs) in the linkage disequilibrium (LD) block of 3p21.31 with chromatin immunoprecipitation-sequencing (ChIP-seq) data of histone modification and tested their association with CRC via a case-control study involving 767 cases and 1397 controls in stage 1 and 528 cases and 678 controls in stage 2. In addition to the tag SNP rs8180040 (odds ratio (OR) = 0.875, 95% confidence interval (95% CI) = 0.793−0.966, P = 0.008, P-FDR (false discovery rate) = 0.040), rs1076394 presented consistently significant associations with CRC risk at both stages with OR = 0.850 (95% CI = 0.771−0.938, P = 0.001, P-FDR = 0.005) under the additive model in combined analyses. Supported by the analyses of data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), it was suggested that rs1076394 served as an expression Quantitative Trait Loci (eQTL) for gene CCDC12 and NME6, while NME6’s expression was obviously higher in CRC tissues. Using biofeature information such as ChIP-seq and RNA sequencing (RNA-seq) data might help researchers to interpret GWAS results and locate functional variants for diseases in the post-GWAS era.
Detection of DNA viruses in prostate cancer
Authors: Smelov Vitaly , Bzhalava Davit , Arroyo Mühr Laila Sara , Eklund Carina , Komyakov Boris , Gorelov Andrey , Dillner Joakim , Hultin Emilie 
Published: April 2016

AbstractWe tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions.
Genome-wide identification of target genes for miR-204 and miR-211 identifies their proliferation stimulatory role in breast cancer cells
Authors: Lee Hyunkyung , Lee Seungyeon , Bae Hansol , Kang Han-Sung , Kim Sun Jung 
Published: April 2016

AbstractMiR-204 and miR-211 (miR-204/211) share the same seed site sequence, targeting many of the same genes. Their role in cancer development remains controversial, as both cell proliferative and suppressive effects have been identified. This study aimed to address the relationship between the two structurally similar microRNAs (miRs) by examining their target genes in depth as well as to reveal their contribution in breast cancer cells. Genome-wide pathway analysis with the dysregulated genes after overexpression of either of the two miRs in MCF-7 breast cancer cell identified the “Cancer”- and “Cell signaling”-related pathway as the top pathway for miR-204 and miR-211, respectively. The majority of the target genes for both miRs notably comprised ones that have been characterized to drive cells anti-tumorigenic. Accordingly, the miRs induced the proliferation of MCF-7 and MDA-MB-231 cells, judged by cell proliferation as well as colony forming assay. Tumor suppressors, MX1 and TXNIP, were proven to be direct targets of the miRs. In addition, a high association was observed between miR-204 and miR-211 expression in breast cancer tissue. Our results indicate that miR-204/211 serve to increase cell proliferation at least in MCF-7 and MDA-MB-231 breast cancer cells by downregulating tumor suppressor genes.
Effect of different levels of nitrogen on rhizosphere bacterial community structure in intensive monoculture of greenhouse lettuce
Authors: Li Jian-Gang , Shen Min-Chong , Hou Jin-Feng , Li Ling , Wu Jun-Xia , Dong Yuan-Hua 
Published: April 2016

AbstractPyrosequencing-based analyses revealed significant effects among low (N50), medium (N80), and high (N100) fertilization on community composition involving a long-term monoculture of lettuce in a greenhouse in both summer and winter. The non-fertilized control (CK) treatment was characterized by a higher relative abundance of Actinobacteria, Acidobacteria, and Chloroflexi; however, the average abundance of Firmicutes typically increased in summer, and the relative abundance of Bacteroidetes increased in winter in the N-fertilized treatments. Principle component analysis showed that the distribution of the microbial community was separated by a N gradient with N80 and N100 in the same group in the summer samples, while CK and N50 were in the same group in the winter samples, with the other N-level treatments existing independently. Redundancy analysis revealed that available N, NO3−-N, and NH4+-N, were the main environmental factors affecting the distribution of the bacterial community. Correlation analysis showed that nitrogen affected the shifts of microbial communities by strongly driving the shifts of Firmicutes, Bacteroidetes, and Proteobacteria in summer samples, and Bacteroidetes, Actinobacteria, and Acidobacteria in winter samples. The study demonstrates a novel example of rhizosphere bacterial diversity and the main factors influencing rizosphere microbial community in continuous vegetable cropping within an intensive greenhouse ecosystem.
HEY1 functions are regulated by its phosphorylation at Ser-68
Authors: López-Mateo Irene , Arruabarrena-Aristorena Amaia , Artaza-Irigaray Cristina , López Juan A. , Calvo Enrique , Belandia Borja 
Published: April 2016

HEY1 (hairy/enhancer-of-split related with YRPW motif 1) is a member of the basic helix–loop–helix-orange (bHLH-O) family of transcription repressors that mediate Notch signalling. HEY1 acts as a positive regulator of the tumour suppressor p53 via still unknown mechanisms. A MALDI-TOF/TOF MS analysis has uncovered a novel HEY1 regulatory phosphorylation event at Ser-68. Strikingly, this single phosphorylation event controls HEY1 stability and function: simulation of HEY1 Ser-68 phosphorylation increases HEY1 protein stability but inhibits its ability to enhance p53 transcriptional activity. Unlike wild-type HEY1, expression of the phosphomimetic mutant HEY1-S68D failed to induce p53-dependent cell cycle arrest and it did not sensitize U2OS cells to p53-activating chemotherapeutic drugs. We have identified two related kinases, STK38 (serine/threonine kinase 38) and STK38L (serine/threonine kinase 38 like), which interact with and phosphorylate HEY1 at Ser-68. HEY1 is phosphorylated at Ser-68 during mitosis and it accumulates in the centrosomes of mitotic cells, suggesting a possible integration of HEY1-dependent signalling in centrosome function. Moreover, HEY1 interacts with a subset of p53-activating ribosomal proteins. Ribosomal stress causes HEY1 relocalization from the nucleoplasm to perinucleolar structures termed nucleolar caps. HEY1 interacts physically with at least one of the ribosomal proteins, RPL11, and both proteins cooperate in the inhibition of MDM2-mediated p53 degradation resulting in a synergistic positive effect on p53 transcriptional activity. HEY1 itself also interacts directly with MDM2 and it is subjected to MDM2-mediated degradation. Simulation of HEY1 Ser-68 phosphorylation prevents its interaction with p53, RPL11 and MDM2 and abolishes HEY1 migration to nucleolar caps upon ribosomal stress. Our findings uncover a novel mechanism for cross-talk between Notch signalling and nucleolar stress.
Return to Work and Social Communication Ability Following Severe Traumatic Brain Injury
Authors: Douglas Jacinta M. , Bracy Christine A. , Snow Pamela C. 
Published: April 2016

Purpose
Return to competitive employment presents a major challenge to adults who survive traumatic brain injury (TBI). This study was undertaken to better understand factors that shape employment outcome by comparing the communication profiles and self-awareness of communication deficits of adults who return to and maintain employment with those who do not.

Method
Forty-six dyads (46 adults with TBI, 46 relatives) were recruited into 2 groups based on the current employment status (employed or unemployed) of participants with TBI. Groups did not differ in regard to sex, age, education, preinjury employment, injury severity, or time postinjury. The La Trobe Communication Questionnaire (Douglas, O'Flaherty, & Snow, 2000) was used to measure communication. Group comparisons on La Trobe Communication Questionnaire scores were analyzed by using mixed 2 × 2 analysis of variance (between factor: employment status; within factor: source of perception).

Results

Analysis yielded a significant group main effect (
p
= .002) and a significant interaction (
p
= .004). The employed group reported less frequent difficulties (self and relatives). Consistent with the interaction, unemployed participants perceived themselves to have less frequent difficulties than their relatives perceived, whereas employed participants reported more frequent difficulties than their relatives.

Conclusion
Communication outcome and awareness of communication deficits play an important role in reintegration to the workplace following TBI.
Analysis and control of photovoltaic‐assisted three‐phase induction machine operating as single‐phase micro‐wind generator
Authors: Chatterjee Arunava , Chatterjee Debashis 
Published: April 2016

An improved control methodology for off‐grid, three‐phase induction machine working as a single‐phase generator is presented in this study. A three‐phase machine made to work as a single‐phase generator has advantages of lower size and cost than their single‐phase equivalent in almost all ratings except in the lower fractional kilowatt (kW) ranges. The three‐phase windings are configured as isolated two equivalent phases in the proposed system for this purpose. The machine uses photovoltaic (PV)‐assisted single‐phase inverter to one of its two phases for variable excitation requirement to cater dynamic loads at different rotor speeds besides having a fixed capacitor to provide bulk excitation. A storage battery is used along with the PV panels to improve the reliability of the scheme during low or no insolation periods. A stator‐flux‐oriented control is implemented for regulating the terminal voltage within specified limit at a fixed frequency. The control strategy ensures fixed load voltage and fixed frequency even with perturbations of load or rotor speed. Different simulation results, verified by suitable experiments using a 1 kW, 415 V laboratory prototype, confirm the suitability of the proposed concept.
Interaction of HIF1α and β-catenin inhibits matrix metalloproteinase 13 expression and prevents cartilage damage in mice
Authors: Bouaziz Wafa , Sigaux Johanna , Modrowski Dominique , Devignes Claire-Sophie , Funck-Brentano Thomas , Richette Pascal , Ea Hang-Korng , Provot Sylvain , Cohen-Solal Martine , Haÿ Eric 
Published: April 2016

Significance
Hypoxia-inducible factor 1α (HIF1α) is important for cell growth and survival. It modulates Wnt signaling, regulating cell differentiation and fate. Osteoarthritis (OA) is an increasingly frequent joint disorder characterized by progressive cartilage breakdown in which Wnt/β-catenin signaling triggers matrix metalloproteinase 13 (MMP13) expression and chondrocyte catabolism. Here we demonstrate HIF1α inhibits β-catenin signaling by blocking transcription factor 4 (TCF4)–β-catenin interaction and down-regulates MMP13 expression, thereby alleviating cartilage lesions, whereas the TCF4–β-catenin signaling induces an OA phenotype in mice. In OA joints, PKF118-310, a small molecule that blocked TCF4–β-catenin interaction, significantly reduced the progression of OA cartilage lesions. Thus, blockade of TCF4–β-catenin signaling by HIF1α represents a promising strategy to prevent articular cartilage loss in OA.
Astrocytes regulate cortical state switching in vivo
Authors: Poskanzer Kira E. , Yuste Rafael 
Published: April 2016

Significance
Astrocytes—a type of glial cell—and neurons function together in neural circuits, but how astrocytes affect circuit function remains poorly understood. By measuring the fluorescent calcium activity of astrocytes while recording the electrophysiological oscillations in the mouse cortex, we find that astrocytes, through regulation of extracellular glutamate, are involved in triggering a slow neuronal rhythm in the brain that has been shown to be important in sleep and memory formation.
Rail-dbGaP: analyzing dbGaP-protected data in the cloud with Amazon Elastic MapReduce
Authors: Nellore Abhinav , Wilks Christopher , Hansen Kasper D. , Leek Jeffrey T. , Langmead Ben 
Published: April 2016

Abstract
Motivation: Public archives contain thousands of trillions of bases of valuable sequencing data. More than 40% of the Sequence Read Archive is human data protected by provisions such as dbGaP. To analyse dbGaP-protected data, researchers must typically work with IT administrators and signing officials to ensure all levels of security are implemented at their institution. This is a major obstacle, impeding reproducibility and reducing the utility of archived data.
Results: We present a protocol and software tool for analyzing protected data in a commercial cloud. The protocol, Rail-dbGaP, is applicable to any tool running on Amazon Web Services Elastic MapReduce. The tool, Rail-RNA v0.2, is a spliced aligner for RNA-seq data, which we demonstrate by running on 9662 samples from the dbGaP-protected GTEx consortium dataset. The Rail-dbGaP protocol makes explicit for the first time the steps an investigator must take to develop Elastic MapReduce pipelines that analyse dbGaP-protected data in a manner compliant with NIH guidelines. Rail-RNA automates implementation of the protocol, making it easy for typical biomedical investigators to study protected RNA-seq data, regardless of their local IT resources or expertise.
Availability and Implementation: Rail-RNA is available from http://rail.bio. Technical details on the Rail-dbGaP protocol as well as an implementation walkthrough are available at https://github.com/nellore/rail-dbgap. Detailed instructions on running Rail-RNA on dbGaP-protected data using Amazon Web Services are available at http://docs.rail.bio/dbgap/.
Contacts: anellore@gmail.com or langmea@cs.jhu.edu
Supplementary information: Supplementary data are available at Bioinformatics online.