bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tumor suppressor TMEM127 regulates insulin sensitivity in a tissue-specific manner
Authors: Srikantan Subramanya , Deng Yilun , Cheng Zi-Ming , Luo Anqi , Qin Yuejuan , Gao Qing , Sande-Docor Glaiza-Mae , Tao Sifan , Zhang Xingyu , Harper Nathan , Shannon Chris E. , Fourcaudot Marcel , Li Zhi , Kasinath Balakuntalam S. , Harrison Stephen , Ahuja Sunil , Reddick Robert L. , Dong Lily Q. , Abdul-Ghani Muhammad , Norton Luke , Aguiar Ricardo C. T. , Dahia Patricia L. M. 
Published: October 2019

AbstractUnderstanding the molecular components of insulin signaling is relevant to effectively manage insulin resistance. We investigated the phenotype of the TMEM127 tumor suppressor gene deficiency in vivo. Whole-body Tmem127 knockout mice have decreased adiposity and maintain insulin sensitivity, low hepatic fat deposition and peripheral glucose clearance after a high-fat diet. Liver-specific and adipose-specific Tmem127 deletion partially overlap global Tmem127 loss: liver Tmem127 promotes hepatic gluconeogenesis and inhibits peripheral glucose uptake, while adipose Tmem127 downregulates adipogenesis and hepatic glucose production. mTORC2 is activated in TMEM127-deficient hepatocytes suggesting that it interacts with TMEM127 to control insulin sensitivity. Murine hepatic Tmem127 expression is increased in insulin-resistant states and is reversed by diet or the insulin sensitizer pioglitazone. Importantly, human liver TMEM127 expression correlates with steatohepatitis and insulin resistance. Our results suggest that besides tumor suppression activities, TMEM127 is a nutrient-sensing component of glucose/lipid homeostasis and may be a target in insulin resistance.
GWAS of mosaic loss of chromosome Y highlights genetic effects on blood cell differentiation
Authors: Terao Chikashi , Momozawa Yukihide , Ishigaki Kazuyoshi , Kawakami Eiryo , Akiyama Masato , Loh Po-Ru , Genovese Giulio , Sugishita Hiroki , Ohta Tazro , Hirata Makoto , Perry John R. B. , Matsuda Koichi , Murakami Yoshinori , Kubo Michiaki , Kamatani Yoichiro 
Published: October 2019

AbstractMosaic loss of chromosome Y (mLOY) is frequently observed in the leukocytes of ageing men. However, the genetic architecture and biological mechanisms underlying mLOY are not fully understood. In a cohort of 95,380 Japanese men, we identify 50 independent genetic markers in 46 loci associated with mLOY at a genome-wide significant level, 35 of which are unreported. Lead markers overlap enhancer marks in hematopoietic stem cells (HSCs, P ≤ 1.0 × 10−6). mLOY genome-wide association study signals exhibit polygenic architecture and demonstrate strong heritability enrichment in regions surrounding genes specifically expressed in multipotent progenitor (MPP) cells and HSCs (P ≤ 3.5 × 10−6). ChIP-seq data demonstrate that binding sites of FLI1, a fate-determining factor promoting HSC differentiation into platelets rather than red blood cells (RBCs), show a strong heritability enrichment (P = 1.5 × 10−6). Consistent with these findings, platelet and RBC counts are positively and negatively associated with mLOY, respectively. Collectively, our observations improve our understanding of the mechanisms underlying mLOY.
Contributions of anterior cingulate cortex and basolateral amygdala to decision confidence and learning under uncertainty
Authors: Stolyarova A. , Rakhshan M. , Hart E. E. , O’Dell T. J. , Peters M. A. K. , Lau H. , Soltani A. , Izquierdo A. 
Published: October 2019

AbstractThe subjective sense of certainty, or confidence, in ambiguous sensory cues can alter the interpretation of reward feedback and facilitate learning. We trained rats to report the orientation of ambiguous visual stimuli according to a spatial stimulus-response rule that must be learned. Following choice, rats could wait a self-timed delay for reward or initiate a new trial. Waiting times increase with discrimination accuracy, demonstrating that this measure can be used as a proxy for confidence. Chemogenetic silencing of BLA shortens waiting times overall whereas ACC inhibition renders waiting times insensitive to confidence-modulating attributes of visual stimuli, suggesting contribution of ACC but not BLA to confidence computations. Subsequent reversal learning is enhanced by confidence. Both ACC and BLA inhibition block this enhancement but via differential adjustments in learning strategies and consistent use of learned rules. Altogether, we demonstrate dissociable roles for ACC and BLA in transmitting confidence and learning under uncertainty.
Metallic porous nitride single crystals at two-centimeter scale delivering enhanced pseudocapacitance
Authors: Xi Shaobo , Lin Guoming , Jin Lu , Li Hao , Xie Kui 
Published: October 2019

AbstractPseudocapacitors that originate from chemisorption contain redox active sites mainly composed of transition metal ions with unsaturated coordination in lattice on the electrode surface. The capacitance is generally dictated by the synergy of the porous microstructure, electronic conduction and active sites in the porous electrode. Here we grow metallic porous nitride single crystals at 2-cm scale to enhance pseudocapacitance through the combination of large surface area with porous microstructure, high conductivity with metallic states and ordered active sites with unsaturated coordination at twisted surfaces. We show the enhanced gravimetric and areal pseudocapacitance and excellent cycling stability both in acidic and alkaline electrolyte with porous MoN, Ta5N6 and TiN single crystals. The long-range ordering of active metal-nitrogen sites account for the fast redox reactions in chemisorption while the high conductivity together with porous microstructure facilitate the charge transfer and species diffusion in electrodes.
The impact of decellularization methods on extracellular matrix derived hydrogels
Authors: Fernández-Pérez Julia , Ahearne Mark 
Published: October 2019

AbstractTissue-derived decellularized biomaterials are ideal for tissue engineering applications as they mimic the biochemical composition of the native tissue. These materials can be used as hydrogels for cell encapsulation and delivery. The decellularization process can alter the composition of the extracellular matrix (ECM) and thus influence the hydrogels characteristics. The aim of this study was to examine the impact of decellularization protocols in ECM-derived hydrogels obtained from porcine corneas. Porcine corneas were isolated and decellularized with SDS, Triton X-100 or by freeze-thaw cycles. All decellularization methods decreased DNA significantly when measured by PicoGreen and visually assessed by the absence of cell nuclei. Collagen and other ECM components were highly retained, as quantified by hydroxyproline content and sGAG, by histological analysis and by SDS-PAGE. Hydrogels obtained by freeze-thaw decellularization were the most transparent. The method of decellularization impacted gelation kinetics assessed by turbidimetric analysis. All hydrogels showed a fibrillary and porous structure determined by cryoSEM. Human corneal stromal cells were embedded in the hydrogels to assess cytotoxicity. SDS decellularization rendered cytotoxic hydrogels, while the other decellularization methods produced highly cytocompatible hydrogels. Freeze-thaw decellularization produced hydrogels with the overall best properties.
Microtubule disruption changes endothelial cell mechanics and adhesion
Authors: Weber Andreas , Iturri Jagoba , Benitez Rafael , Zemljic-Jokhadar Spela , Toca-Herrera José L. 
Published: October 2019

AbstractThe interest in studying the mechanical and adhesive properties of cells has increased in recent years. The cytoskeleton is known to play a key role in cell mechanics. However, the role of the microtubules in shaping cell mechanics is not yet well understood. We have employed Atomic Force Microscopy (AFM) together with confocal fluorescence microscopy to determine the role of microtubules in cytomechanics of Human Umbilical Vein Endothelial Cells (HUVECs). Additionally, the time variation of the adhesion between tip and cell surface was studied. The disruption of microtubules by exposing the cells to two colchicine concentrations was monitored as a function of time. Already, after 30 min of incubation the cells stiffened, their relaxation times increased (lower fluidity) and the adhesion between tip and cell decreased. This was accompanied by cytoskeletal rearrangements, a reduction in cell area and changes in cell shape. Over the whole experimental time, different behavior for the two used concentrations was found while for the control the values remained stable. This study underlines the role of microtubules in shaping endothelial cell mechanics.
Human single-chain antibodies that neutralize Pseudomonas aeruginosa-exotoxin A-mediated cellular apoptosis
Authors: Santajit Sirijan , Seesuay Watee , Mahasongkram Kodchakorn , Sookrung Nitat , Ampawong Sumate , Reamtong Onrapak , Diraphat Pornphan , Chaicumpa Wanpen , Indrawattana Nitaya 
Published: October 2019

AbstractTargeting bacterial virulence factors directly provides a new paradigm for the intervention and treatment of bacterial diseases. Pseudomonas aeruginosa produces a myriad of virulence factors to cause fatal diseases in humans. In this study, human single-chain antibodies (HuscFvs) that bound to P. aeruginosa exotoxin A (ETA) were generated by phage display technology using recombinant ETA, ETA-subdomains and the synthetic peptide of the ETA-catalytic site as baits for selecting ETA-bound-phages from the human-scFv phage display library. ETA-bound HuscFvs derived from three phage-transfected E. coli clones neutralized the ETA-induced mammalian cell apoptosis. Computerized simulation demonstrated that these HuscFvs used several residues in their complementarity-determining regions (CDRs) to form contact interfaces with the critical residues in ETA-catalytic domain essential for ADP-ribosylation of eukaryotic elongation factor 2, which should consequently rescue ETA-exposed-cells from apoptosis. The HuscFv-treated ETA-exposed cells also showed decremented apoptosis-related genes, i.e., cas3 and p53. The effective HuscFvs have high potential for future evaluation in animal models and clinical trials as a safe, novel remedy for the amelioration of exotoxin A-mediated pathogenesis. HuscFvs may be used either singly or in combination with the HuscFv cognates that target other P. aeruginosa virulence factors as an alternative therapeutic regime for difficult-to-treat infections.
Flexible High-Color-Purity Structural Color Filters Based on a Higher-Order Optical Resonance Suppression
Authors: Lee Kyu-Tae , Han Sung Yong , Li Zijia , Baac Hyoung Won , Park Hui Joon 
Published: October 2019

AbstractWe present flexible transmissive structural color filters with high-color-purity based on a higher-order resonance suppression by inserting an ultrathin absorbing layer in the middle of a cavity. A 3rd order Fabry–Pérot (F-P) resonance, which exhibits a narrower bandwidth than a fundamental F-P resonance, is used to produce transmissive colors with an improved color purity. The thin absorbing layer is properly placed at a center of the cavity to highly suppress only a 5th order F-P resonance appearing at a short wavelength range while not affecting the 3rd order F-P resonance for color generation, thus being able to attain the high-color-purity transmissive colors without reducing a transmission efficiency. In addition, angle-insensitive properties are achieved by compensating a net phase shift with a dielectric overlay and using a material with a high refractive index for the cavity medium. Moreover, the transmissive colors on a flexible substrate are demonstrated, presenting that changes in both the resonance wavelength and the transmission efficiency are nearly negligible when the color filters are bent with a bending radius of 5 mm and over 3000 times bending tests. The described approach could pave the way for various applications, such as colored displays, decorative solar panels, and image sensors.
An interactive and intuitive visualisation method for X-ray computed tomography data of biological samples in 3D Portable Document Format
Authors: Tesařová Markéta , Heude Eglantine , Comai Glenda , Zikmund Tomáš , Kaucká Markéta , Adameyko Igor , Tajbakhsh Shahragim , Kaiser Jozef 
Published: October 2019

Abstract3D imaging approaches based on X-ray microcomputed tomography (microCT) have become increasingly accessible with advancements in methods, instruments and expertise. The synergy of material and life sciences has impacted biomedical research by proposing new tools for investigation. However, data sharing remains challenging as microCT files are usually in the range of gigabytes and require specific and expensive software for rendering and interpretation. Here, we provide an advanced method for visualisation and interpretation of microCT data with small file formats, readable on all operating systems, using freely available Portable Document Format (PDF) software. Our method is based on the conversion of volumetric data into interactive 3D PDF, allowing rotation, movement, magnification and setting modifications of objects, thus providing an intuitive approach to analyse structures in a 3D context. We describe the complete pipeline from data acquisition, data processing and compression, to 3D PDF formatting on an example of craniofacial anatomical morphology in the mouse embryo. Our procedure is widely applicable in biological research and can be used as a framework to analyse volumetric data from any research field relying on 3D rendering and CT-biomedical imaging.
The vernalisation regulator FLOWERING LOCUS C is differentially expressed in biennial and annual Brassica napus
Authors: Schiessl Sarah V. , Quezada-Martinez Daniela , Tebartz Ellen , Snowdon Rod J. , Qian Lunwen 
Published: October 2019

AbstractPlants in temperate areas evolved vernalisation requirement to avoid pre-winter flowering. In Brassicaceae, a period of extended cold reduces the expression of the flowering inhibitor FLOWERING LOCUS C (FLC) and paves the way for the expression of downstream flowering regulators. As with all polyploid species of the Brassicaceae, the model allotetraploid Brassica napus (rapeseed, canola) is highly duplicated and carries 9 annotated copies of Bna.FLC. To investigate whether these multiple homeologs and paralogs have retained their original function in vernalisation or undergone subfunctionalisation, we compared the expression patterns of all 9 copies between vernalisation-dependent (biennial, winter type) and vernalisation-independent (annual, spring type) accessions, using RT-qPCR with copy-specific primers and RNAseq data from a diversity set. Our results show that only 3 copies – Bna.FLC.A03b, Bna.FLC.A10 and to some extent Bna.FLC.C02 – are differentially expressed between the two growth types, showing that expression of the other 6 copies does not correlate with growth type. One of those 6 copies, Bna.FLC.C03b, was not expressed at all, indicating a pseudogene, while three further copies, Bna.FLC.C03a and Bna.FLC.C09ab, did not respond to cold treatment. Sequence variation at the COOLAIR binding site of Bna.FLC.A10 was found to explain most of the variation in gene expression. However, we also found that Bna.FLC.A10 expression is not fully predictive of growth type.
Genotoxic effects of tobacco use in residents of hilly areas and foot hills of Western Ghats, Southern India
Authors: Chandirasekar R. , Murugan K. , Muralisankar T. , Uthayakumar V. , Jayakumar R. , Mohan K. , Vasugi C. , Mathivanan R. , Mekala S. , Jagateesh A. , Suresh K. 
Published: October 2019

AbstractSmoking and smokeless tobacco consumption is a significant risk factor that provokes genetic alterations. The present investigation was to evaluate the biomarkers of genotoxicity including micronucleus (MN), chromosome aberrations (CA) and DNA strand breaks among tobacco consumers and control individuals residing in hilly areas of Western Ghats, Tamilnadu, South India. This study included 268 tobacco consumers with equal number of controls. The tobacco consumers were divided into Group I (<10 years of tobacco consumption with an age range from 15 to 35 years) and group II (>10 years consumption above 35 years of age). Chromosome aberration (CA) and comet assay were performed using blood and micronucleus assay from exfoliated buccal epithelial cells obtained from tobacco consumers and controls. Elevated levels of CA were found in group II (Chromatid type: 2.39 ± 1.13 and chromosome type: 1.44 ± 1.24) exposed subjects, high micronucleus and DNA damage (TL:4.48 ± 1.24 and TM:3.40 ± 1.58) levels were significantly (p < 0.05) observed in both smoking and smokeless tobacco consumers when comparison with group I and controls. This study also observed a lack of awareness among the tobacco consumers about the harmful health effects of tobacco. Tobacco consumption contributes to the significant alteration in genetic materials. In addition, a high rate of spontaneous abortion was also seen in the studied population.
Fucosylated inhibitors of recently identified bangle lectin from Photorhabdus asymbiotica
Authors: Paulíková Gita , Houser Josef , Kašáková Martina , Oroszová Beáta , Bertolotti Benedetta , Parkan Kamil , Moravcová Jitka , Wimmerová Michaela 
Published: October 2019

AbstractA recently described bangle lectin (PHL) from the bacterium Photorhabdus asymbiotica was identified as a mainly fucose-binding protein that could play an important role in the host-pathogen interaction and in the modulation of host immune response. Structural studies showed that PHL is a homo-dimer that contains up to seven l-fucose-specific binding sites per monomer. For these reasons, potential ligands of the PHL lectin: α-l-fucopyranosyl-containing mono-, di-, tetra-, hexa- and dodecavalent ligands were tested. Two types of polyvalent structures were investigated – calix[4]arenes and dendrimers. The shared feature of all these structures was a C-glycosidic bond instead of the more common but physiologically unstable O-glycosidic bond. The inhibition potential of the tested structures was assessed using different techniques – hemagglutination, surface plasmon resonance, isothermal titration calorimetry, and cell cross-linking. All the ligands proved to be better than free l-fucose. The most active hexavalent dendrimer exhibited affinity three orders of magnitude higher than that of standard l-fucose. To determine the binding mode of some ligands, crystal complex PHL/fucosides 2 – 4 were prepared and studied using X-ray crystallography. The electron density in complexes proved the presence of the compounds in 6 out of 7 fucose-binding sites.
Simulated microgravity inhibits C2C12 myogenesis via phospholipase D2-induced Akt/FOXO1 regulation
Authors: Baek Mi-Ock , Ahn Chi Bum , Cho Hye-Jeong , Choi Ji-Young , Son Kuk Hui , Yoon Mee-Sup 
Published: October 2019

AbstractThe skeletal muscle system has evolved to maintain body posture against a constant gravitational load. Mammalian target of rapamycin (mTOR) regulates the mechanically induced increase in the skeletal muscle mass. In the present study, we investigated mTOR pathway in C2C12 myoblasts in a model of mechanical unloading by creating a simulated microgravity (SM) using 3 D clinorotation. SM decreased the phosphorylation of Akt at Ser 473, which was mediated by mTOR complex 2 (mTORC2), in C2C12 myoblasts, leading to a decrease in the cell growth rate. Subsequently, SM inhibited C2C12 myogenesis in an Akt-dependent manner. In addition, SM increased the phospholipase D (PLD) activity by enhancing PLD2 expression, resulting in the dissociation of mSIN1 from the mTORC2, followed by decrease in the phosphorylation of Akt at Ser 473, and FOXO1 at Ser 256 in C2C12 myoblasts. Exposure to SM decreased the autophagic flux of C2C12 myoblasts by regulation of mRNA level of autophagic genes in a PLD2 and FOXO1-dependent manner, subsequently, resulting in a decrease in the C2C12 myogenesis. In conclusion, by analyzing the molecular signature of C2C12 myogenesis using SM, we suggest that the regulatory axis of the PLD2 induced Akt/FOXO1, is critical for C2C12 myogenesis.
Autoantibody levels are associated with acute kidney injury, anemia and post-discharge morbidity and mortality in Ugandan children with severe malaria
Authors: Rivera-Correa Juan , Conroy Andrea L. , Opoka Robert O. , Batte Anthony , Namazzi Ruth , Ouma Benson , Bangirana Paul , Idro Richard , Schwaderer Andrew L. , John Chandy C. , Rodriguez Ana 
Published: October 2019

AbstractAutoantibodies targeting host antigens contribute to autoimmune disorders, frequently occur during and after infections and have been proposed to contribute to malaria-induced anemia. We measured anti-phosphatidylserine (PS) and anti-DNA antibody levels in 382 Ugandan children prospectively recruited in a study of severe malaria (SM). High antibody levels were defined as antibody levels greater than the mean plus 3 standard deviations of community children (CC). We observed increases in median levels of anti-PS and anti-DNA antibodies in children with SM compared to CC (p < 0.0001 for both). Children with severe malarial anemia were more likely to have high anti-PS antibodies than children with cerebral malaria (16.4% vs. 7.4%), p = 0.02. Increases in anti-PS and anti-DNA antibodies were associated with decreased hemoglobin (p < 0.05). A one-unit increase in anti-DNA antibodies was associated with a 2.99 (95% CI, 1.68, 5.31) increase odds of acute kidney injury (AKI) (p < 0.0001). Elevated anti-PS and anti-DNA antibodies were associated with post-discharge mortality (p = 0.031 and p = 0.042, respectively). Children with high anti-PS antibodies were more likely to have multiple hospital readmissions compared to children with normal anti-PS antibody levels (p < 0.05). SM is associated with increased autoantibodies against PS and DNA. Autoantibodies were associated with anemia, AKI, post-discharge mortality, and hospital readmission.
Decision-making criteria for damage control surgery in Japan
Authors: Urushibata Nao , Murata Kiyoshi , Otomo Yasuhiro 
Published: October 2019

AbstractControversy still remains regarding the optimal criteria for selecting damage control surgery (DCS). Our objective was to propose an indication for implementing DCS for abdominal trauma requiring emergency laparotomy. This was a multicenter, retrospective, observational study that used data from the Japan Trauma Data Bank. Patients who underwent emergency laparotomy were included. We compared the patients regarding the performance of DCS. Of the 4447 patients included in the study, 532 patients were in the DCS group and 3915 patients were in the non-DCS group. Logistic regression analysis revealed that body temperature, level of consciousness (Glasgow Coma Scale), and type of injury (blunt or penetrating) were independent predictors of DCS. Using these predictors, we created the Damage Control Indication Detecting score. The score showed a positive correlation with mortality. The score was obtained as 5 of 9 points in total, revealing mortality of 30.8%, sensitivity of 64.8%, and specificity of 70.0%. The area under the curve for the receiver operating characteristic curve was 0.715. This score can help surgeons determine when to perform DCS. However, more than 95% of trauma cases in Japan involve blunt injuries, suggesting that the results of our study may not be applicable internationally.