bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZikaVR: An Integrated Zika Virus Resource for Genomics, Proteomics, Phylogenetic and Therapeutic Analysis
Authors: Gupta Amit Kumar , Kaur Karambir , Rajput Akanksha , Dhanda Sandeep Kumar , Sehgal Manika , Khan Md. Shoaib , Monga Isha , Dar Showkat Ahmad , Singh Sandeep , Nagpal Gandharva , Usmani Salman Sadullah , Thakur Anamika , Kaur Gazaldeep , Sharma Shivangi , Bhardwaj Aman , Qureshi Abid , Raghava Gajendra Pal Singh , Kumar Manoj 
Published: September 2016

AbstractCurrent Zika virus (ZIKV) outbreaks that spread in several areas of Africa, Southeast Asia, and in pacific islands is declared as a global health emergency by World Health Organization (WHO). It causes Zika fever and illness ranging from severe autoimmune to neurological complications in humans. To facilitate research on this virus, we have developed an integrative multi-omics platform; ZikaVR (http://bioinfo.imtech.res.in/manojk/zikavr/), dedicated to the ZIKV genomic, proteomic and therapeutic knowledge. It comprises of whole genome sequences, their respective functional information regarding proteins, genes, and structural content. Additionally, it also delivers sophisticated analysis such as whole-genome alignments, conservation and variation, CpG islands, codon context, usage bias and phylogenetic inferences at whole genome and proteome level with user-friendly visual environment. Further, glycosylation sites and molecular diagnostic primers were also analyzed. Most importantly, we also proposed potential therapeutically imperative constituents namely vaccine epitopes, siRNAs, miRNAs, sgRNAs and repurposing drug candidates.
Extracellular cGMP Modulates Learning Biphasically by Modulating Glycine Receptors, CaMKII and Glutamate-Nitric Oxide-cGMP Pathway
Authors: Cabrera-Pastor Andrea , Malaguarnera Michele , Taoro-Gonzalez Lucas , Llansola Marta , Felipo Vicente 
Published: September 2016

AbstractIt has been proposed that extracellular cGMP modulates the ability to learn a Y maze task, but the underlying mechanisms remained unknown. Here we show that extracellular cGMP, at physiological concentrations, modulates learning in the Y maze in a biphasic way by modulating the glutamate-nitric oxide-cGMP pathway in cerebellum. Extracellular cGMP reduces glycine receptors activation inducing a voltage-dependent calcium-channels-mediated increase of calcium in Purkinje neurons. This calcium increase modulates CaMKII phosphorylation in a biphasic way. When basal calcium concentration is low extracellular cGMP reduces CaMKII phosphorylation, increasing nitric oxide synthase activity, the glutamate-NO-cGMP pathway function and learning ability. When basal calcium is normal extracellular cGMP increases CaMKII phosphorylation, reducing nitric oxide synthase activity, the pathway function and learning. These data unveil new mechanisms modulating learning in the Y maze and likely other learning types which may be therapeutic targets to improve learning in pathological situations associated with altered cGMP levels.
Horizontal gene transfer drives adaptive colonization of apple trees by the fungal pathogen Valsa mali
Authors: Yin Zhiyuan , Zhu Baitao , Feng Hao , Huang Lili 
Published: September 2016

AbstractHorizontal gene transfer (HGT) often has strong benefits for fungi. In a study of samples from apple canker in Shaanxi Province, China, diverse microbes, along with the necrotrophic pathogen Valsa mali, were found to colonize the apple bark, thus providing ample opportunity for HGT to occur. In the present study, we identified 32 HGT events in V. mali by combining phyletic distribution-based methods with phylogenetic analyses. Most of these HGTs were from bacteria, whereas several others were from eukaryotes. Three HGTs putatively functioned in competition with actinomycetes, some of which showed a significant inhibitory effect on V. mali. Three HGTs that were probably involved in nitrogen uptake were also identified. Ten HGTs were thought to be involved in pathogenicity because they were related to known virulence factors, including cell wall-degrading enzymes and candidate effector proteins. HGT14, together with HGT32, was shown to contribute to bleomycin resistance of V. mali.These results suggest that HGT drives the adaptive evolution of V. mali. The HGTs identified here provide new clues for unveiling the adaptation mechanisms and virulence determinants of V. mali.
Nitroaromatic explosives detection using electrochemically exfoliated graphene
Authors: Yew Ying Teng , Ambrosi Adriano , Pumera Martin 
Published: September 2016

AbstractDetection of nitroaromatic explosives is of paramount importance from security point of view. Graphene sheets obtained from the electrochemical anodic exfoliation of graphite foil in different electrolytes (LiClO4 and Na2SO4) were compared and tested as electrode material for the electrochemical detection of 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT) in seawater. Voltammetry analysis demonstrated the superior electrochemical performance of graphene produced in LiClO4, resulting in higher sensitivity and linearity for the explosives detection and lower limit of detection (LOD) compared to the graphene obtained in Na2SO4. We attribute this to the presence of oxygen functionalities onto the graphene material obtained in LiClO4 which enable charge electrostatic interactions with the –NO2 groups of the analyte, in addition to π-π stacking interactions with the aromatic moiety. Research findings obtained from this study would assist in the development of portable devices for the on-site detection of nitroaromatic explosives.
Superfluidity enhanced by spin-flip tunnelling in the presence of a magnetic field
Authors: Zheng Jun-Hui , Wang Daw-Wei , Juzeliūnas Gediminas 
Published: September 2016

AbstractIt is well-known that when the magnetic field is stronger than a critical value, the spin imbalance can break the Cooper pairs of electrons and hence hinder the superconductivity in a spin-singlet channel. In a bilayer system of ultra-cold Fermi gases, however, we demonstrate that the critical value of the magnetic field at zero temperature can be significantly increased by including a spin-flip tunnelling, which opens a gap in the spin-triplet channel near the Fermi surface and hence reduces the influence of the effective magnetic field on the superfluidity. The phase transition also changes from first order to second order when the tunnelling exceeds a critical value. Considering a realistic experiment, this mechanism can be implemented by applying an intralayer Raman coupling between the spin states with a phase difference between the two layers.
Identification of Doxorubicin as an Inhibitor of the IRE1α-XBP1 Axis of the Unfolded Protein Response
Authors: Jiang Dadi , Lynch Connor , Medeiros Bruno C. , Liedtke Michaela , Bam Rakesh , Tam Arvin B. , Yang Zhifen , Alagappan Muthuraman , Abidi Parveen , Le Quynh-Thu , Giaccia Amato J. , Denko Nicholas C. , Niwa Maho , Koong Albert C. 
Published: September 2016

AbstractActivation of the IRE1α-XBP1 branch of the unfolded protein response (UPR) has been implicated in multiple types of human cancers, including multiple myeloma (MM). Through anin silicodrug discovery approach based on protein-compound virtual docking, we identified the anthracycline antibiotic doxorubicin as anin vitroandin vivoinhibitor of XBP1 activation, a previously unknown activity for this widely utilized cancer chemotherapeutic drug. Through a series of mechanistic and phenotypic studies, we showed that this novel activity of doxorubicin was not due to inhibition of topoisomerase II (Topo II). Consistent with its inhibitory activity on the IRE1α-XBP1 branch of the UPR, doxorubicin displayed more potent cytotoxicity against MM cell lines than other cancer cell lines that have lower basal IRE1α-XBP1 activity. In addition, doxorubicin significantly inhibited XBP1 activation in CD138+tumor cells isolated from MM patients. Our findings suggest that the UPR-modulating activity of doxorubicin may be utilized clinically to target IRE1α–XBP1-dependent tumors such as MM.
Ursolic acid-mediated apoptosis of K562 cells involves Stat5/Akt pathway inhibition through the induction of Gfi-1
Authors: Lin Ze , Jiang Jikai , Liu Xiao-Shan 
Published: September 2016

AbstractUrsolic acid (UA) is a promising natural compound for cancer prevention and therapy. We previously reported that UA induced apoptosis in CML-derived K562 cells. Here we show that the apoptotic process is accompanied by down-regulation of Bcl-xL and Mcl-1 expression and dephosphorylation of Bad. These events are associated with Stat5 inhibition, which is partially mediated through elevated expression of transcriptional repressor Gfi-1. Gfi-1 knockdown using siRNA abrogates the ability of UA to decrease Stat5b expression and attenuates apoptosis induction by UA. We also demonstrate that UA suppresses the Akt kinase activity by inhibiting Akt1/2 expression, which correlates with Stat5 inhibition. Stat5 activity inhibited by a chemical inhibitor or siRNA, Akt1/2 mRNA expression is suppressed. Moreover, we show that UA exerts growth-inhibition in Imatinib-resistant K562/G01. UA has synergistic effects when used in combination with Imatinib in both K562 and K562/G01. Altogether, the data provide evidence that UA’s pro-apoptotic effect in K562 cells is associated with the Gfi-1/Stat5/Akt pathway. The findings indicate that UA could potentially be a useful agent in the treatment of CML.
Association of non-alcoholic fatty liver disease with major adverse cardiovascular events: A systematic review and meta-analysis
Authors: Wu Shunquan , Wu Fuquan , Ding Yingying , Hou Jun , Bi Jingfeng , Zhang Zheng 
Published: September 2016

AbstractIncreasing evidence connects non-alcoholic fatty liver disease (NAFLD) to cardiovascular disease (CVD). The aim of this study is to assess whether and to what extent the excess risk of CVD is conferred by NAFLD in a meta-analysis. We systematically searched PubMed, EmBase, Web of Science, and Cochrane Library for reports published between 1965 and July 3, 2015. Studies that reported data on association between NAFLD and adverse cardiovascular events or mortality were included. Thirty-four studies (164,494 participants, 21 cross-sectional studies, and 13 cohort studies) were included. NAFLD was not associated with overall mortality (HR = 1.14, 95% CI: 0.99–1.32) and CVD mortality (HR = 1.10, 95% CI: 0.86–1.41). However, NAFLD was associated with an increased risk of prevalent (OR = 1.81, 95% CI: 1.23–2.66) and incident (HR = 1.37, 95% CI: 1.10–1.72) CVD. For some specific CVDs, NAFLD was associated with an increased risk of prevalent (OR = 1.87, 95% CI: 1.47–2.37) and incident (HR = 2.31, 95% CI: 1.46–3.65) coronary artery disease (CAD), prevalent (OR = 1.24, 95% CI: 1.14–1.36) and incident (HR = 1.16, 95% CI: 1.06–1.27) hypertension, and prevalent (OR = 1.32, 95% CI: 1.07–1.62) atherosclerosis. In conclusion, the presence of NAFLD is associated with an increased risk of major adverse cardiovascular events, although it is not related to mortality from all causes or CVD.
Potential of in vivo real-time gastric gas profiling: a pilot evaluation of heat-stress and modulating dietary cinnamon effect in an animal model
Authors: Ou Jian Zhen , Cottrell Jeremy J. , Ha Nam , Pillai Naresh , Yao Chu K. , Berean Kyle J. , Ward Stephanie A. , Grando Danilla , Muir Jane G. , Harrison Christopher J. , Wijesiriwardana Udani , Dunshea Frank R. , Gibson Peter R. , Kalantar-zadeh Kourosh 
Published: September 2016

AbstractGastroenterologists are still unable to differentiate between some of the most ordinary disorders of the gut and consequently patients are misdiagnosed. We have developed a swallowable gas sensor capsule for addressing this. The gases of the gut are the by-product of the fermentation processes during digestion, affected by the gut state and can consequently provide the needed information regarding the health of the gut. Here we present the first study on gas sensor capsules for revealing the effect of a medical supplement in an animal (pig) model. We characterise the real-time alterations of gastric-gas in response to environmental heat-stress and dietary cinnamon and use the gas profiles for understanding the bio-physiological changes. Under no heat-stress, feeding increases gastric CO2 concentration, while dietary cinnamon reduces it due to decrease in gastric acid and pepsin secretion. Alternatively, heat-stress leads to hyperventilation in pigs, which reduces CO2 concentration and with the cinnamon treatment, CO2 diminishes even more, resulting in health improvement outcomes. Overall, a good repeatability in gas profiles is also observed. The model demonstrates the strong potential of real-time gas profiler in providing new physiological information that will impact understanding of therapeutics, presenting a highly reliable device for monitoring/diagnostics of gastrointestinal disorders.
A comprehensive validation of HBV-related acute-on-chronic liver failure models to assist decision-making in targeted therapeutics
Authors: Shen Yi , Wang Xulin , Zhang Sheng , Qin Gang , Liu Yanmei , Lu Yihua , Liang Feng , Zhuang Xun 
Published: September 2016

AbstractThis research utilized an external longitudinal dataset of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) to compare and validate various predictive models that support the current recommendations to select the most effective predictive risk models to estimate short- and long-term mortality and facilitate decision-making about preferable therapeutics for HBV-ACLF patients. Twelve ACLF prognostic models were developed after a systematic literature search using the longitudinal data of 232 HBV-ACLF patients on the waiting list for liver transplantation (LT). Four statistical measures, the constant (A) and slope (B) of the fitted line, the area under the curve (C) and the net benefit (D), were calculated to assess and compare the calibration, discrimination and clinical usefulness of the 12 predictive models. According to the model calibration and discrimination, the logistic regression models (LRM2) and the United Kingdom model of end-stage liver disease(UKELD) were selected as the best predictive models for both 3-month and 5-year outcomes. The decision curve summarizes the benefits of intervention relative to the costs of unnecessary treatment. After the comprehensive validation and comparison of the currently used models, LRM2 was confirmed as a markedly effective prognostic model for LT-free HBV-ACLF patients for assisting targeted and standardized therapeutic decisions.
Chronic Kappa opioid receptor activation modulates NR2B: Implication in treatment resistant depression
Authors: Dogra Shalini , Kumar Ajeet , Umrao Deepmala , Sahasrabuddhe Amogh A. , Yadav Prem N. 
Published: September 2016

AbstractPsychotomimetic and prodepressive effect by kappa opioid receptor (KOR) activation in rodents and human is widely known. Significantly, recent clinical investigations demonstrated the salutary effects of KOR antagonists in patients with treatment resistant depression, indicating essential role of KOR signaling in refractory depression. This study was undertaken to reveal the molecular determinant of KOR mediated depression and antidepressant response of KOR antagonist. We observed that chronic KOR activation by U50488, a selective KOR agonist, significantly increased depression like symptoms (behavioral despair, anhedonia and sociability) in C57BL/6J mice, which were blocked by KOR antagonist norBNI and antidepressant imipramine, but not by fluoxetine or citalopram. Further, chronic KOR activation increased phosphorylation of NR2B subunit of NMDA at tyrosine 1472 (pNR2B NMDA) in the hippocampus, but not in the cortex. Similar to behavioral effects norBNI and imipramine, but not SSRIs, blocked NR2B phosphorylation. Moreover, KOR induced depression like behaviors were reversed by NR2B selective inhibitor Ro 25-6981. Mechanistic studies in primary cultured neurons and brain tissues using genetic and pharmacological approaches revealed that stimulation of KOR modulates several molecular correlates of depression. Thus, these findings elucidate molecular mechanism of KOR signaling in treatment resistant depression like behaviors in mice.
Ultrasensitive and low-volume point-of-care diagnostics on flexible strips – a study with cardiac troponin biomarkers
Authors: Shanmugam Nandhinee Radha , Muthukumar Sriram , Prasad Shalini 
Published: September 2016

AbstractWe demonstrate a flexible, mechanically stable, and disposable electrochemical sensor platform for monitoring cardiac troponins through the detection and quantification of cardiac Troponin-T (cTnT). We designed and fabricated nanostructured zinc oxide (ZnO) sensing electrodes on flexible porous polyimide substrates. We demonstrate ultrasensitive detection is capable at very low sample volumes due to the confinement phenomenon of target species within the ZnO nanostructures leading to enhancement of biomolecular binding on the sensor electrode surface. The performance of the ZnO nanostructured sensor electrode was evaluated against gold and nanotextured ZnO electrodes. The electrochemical sensor functions on affinity based immunoassay principles whereby monoclonal antibodies for cTnT were immobilized on the sensor electrodes using thiol based chemistry. Detection of cTnT in phosphate buffered saline (PBS) and human serum (HS) buffers was achieved at low sample volumes of 20 μL using non-faradaic electrochemical impedance spectroscopy (EIS). Limit of detection (LOD) of 1E-4 ng/mL (i.e. 1 pg/mL) at 7% CV (coefficient of variation) for cTnT in HS was demonstrated on nanostructured ZnO electrodes. The mechanical integrity of the flexible biosensor platform was demonstrated with cyclic bending tests. The sensor performed within 12% CV after 100 bending cycles demonstrating the robustness of the nanostructured ZnO electrochemical sensor platform.
Protein aggregation activates erratic stress response in dietary restricted yeast cells
Authors: Bhadra Ankan Kumar , Das Eshita , Roy Ipsita 
Published: September 2016

AbstractChronic stress and prolonged activation of defence pathways have deleterious consequences for the cell. Dietary restriction is believed to be beneficial as it induces the cellular stress response machinery. We report here that although the phenomenon is beneficial in a wild-type cell, dietary restriction leads to an inconsistent response in a cell that is already under proteotoxicity-induced stress. Using a yeast model of Huntington’s disease, we show that contrary to expectation, aggregation of mutant huntingtin is exacerbated and activation of the unfolded protein response pathway is dampened under dietary restriction. Global proteomic analysis shows that when exposed to a single stress, either protein aggregation or dietary restriction, the expression of foldases like peptidyl-prolyl isomerase, is strongly upregulated. However, under combinatorial stress, this lead is lost, which results in enhanced protein aggregation and reduced cell survival. Successful designing of aggregation-targeted therapeutics will need to take additional stressors into account.
A highly efficient sorbitol dehydrogenase from Gluconobacter oxydans G624 and improvement of its stability through immobilization
Authors: Kim Tae-Su , Patel Sanjay K. S. , Selvaraj Chandrabose , Jung Woo-Suk , Pan Cheol-Ho , Kang Yun Chan , Lee Jung-Kul 
Published: September 2016

AbstractA sorbitol dehydrogenase (GoSLDH) from Gluconobacter oxydans G624 (G. oxydans G624) was expressed in Escherichia coli BL21(DE3)-CodonPlus RIL. The complete 1455-bp codon-optimized gene was amplified, expressed, and thoroughly characterized for the first time. GoSLDH exhibited Km and kcat values of 38.9 mM and 3820 s−1 toward L-sorbitol, respectively. The enzyme exhibited high preference for NADP+ (vs. only 2.5% relative activity with NAD+). GoSLDH sequencing, structure analyses, and biochemical studies, suggested that it belongs to the NADP+-dependent polyol-specific long-chain sorbitol dehydrogenase family. GoSLDH is the first fully characterized SLDH to date, and it is distinguished from other L-sorbose-producing enzymes by its high activity and substrate specificity. Isothermal titration calorimetry showed that the protein binds more strongly to D-sorbitol than other L-sorbose-producing enzymes, and substrate docking analysis confirmed a higher turnover rate. The high oxidation potential of GoSLDH for D-sorbitol was confirmed by cyclovoltametric analysis. Further, stability of GoSLDH significantly improved (up to 13.6-fold) after cross-linking of immobilized enzyme on silica nanoparticles and retained 62.8% residual activity after 10 cycles of reuse. Therefore, immobilized GoSLDH may be useful for L-sorbose production from D-sorbitol.
Dynamics of genome change among Legionella species
Authors: Joseph Sandeep J. , Cox Daniel , Wolff Bernard , Morrison Shatavia S. , Kozak-Muiznieks Natalia A. , Frace Michael , Didelot Xavier , Castillo-Ramirez Santiago , Winchell Jonas , Read Timothy D. , Dean Deborah 
Published: September 2016

AbstractLegionella species inhabit freshwater and soil ecosystems where they parasitize protozoa. L. pneumonphila (LP) serogroup-1 (Lp1) is the major cause of Legionnaires’ Disease (LD), a life-threatening pulmonary infection that can spread systemically. The increased global frequency of LD caused by Lp and non-Lp species underscores the need to expand our knowledge of evolutionary forces underlying disease pathogenesis. Whole genome analyses of 43 strains, including all known Lp serogroups 1–17 and 17 emergent LD-causing Legionella species (of which 33 were sequenced in this study) in addition to 10 publicly available genomes, resolved the strains into four phylogenetic clades along host virulence demarcations. Clade-specific genes were distinct for genetic exchange and signal-transduction, indicating adaptation to specific cellular and/or environmental niches. CRISPR spacer comparisons hinted at larger pools of accessory DNA sequences in Lp than predicted by the pan-genome analyses. While recombination within Lp was frequent and has been reported previously, population structure analysis identified surprisingly few DNA admixture events between species. In summary, diverse Legionella LD–causing species share a conserved core-genome, are genetically isolated from each other, and selectively acquire genes with potential for enhanced virulence.