bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study identifies glutamate ionotropic receptor GRIA4 as a risk gene for comorbid nicotine dependence and major depression
Authors: Zhou Hang , Cheng Zhongshan , Bass Nicholas , Krystal John H. , Farrer Lindsay A. , Kranzler Henry R. , Gelernter Joel 
Published: October 2018

Abstract
Smoking and major depression frequently co-occur, at least in part due to shared genetic risk. However, the nature of the shared genetic basis is poorly understood. To detect genetic risk variants for comorbid nicotine dependence (ND) and major depression (MD), we conducted genome-wide association study (GWAS) in two samples of African-American participants (Yale-Penn 1 and 2) using linear mixed model, followed by meta-analysis. 3724 nicotine-exposed subjects were analyzed: 2596 from Yale-Penn-1 and 1128 from Yale-Penn-2. Continuous measures (Fagerström Test for Nicotine Dependence (FTND) scores and DSM-IV MD criteria) rather than disorder status were used to maximize the power of the GWAS. Genotypes were ascertained using the Illumina HumanOmni1-Quad array (Yale-Penn-1 sample) or the Illumina HumanCore Exome array (Yale-Penn-2 sample), followed by imputation based on the 1000 Genomes reference panel. An intronic variant at the GRIA4 locus, rs68081839, was significantly associated with ND–MD comorbidity (β = 0.69 [95% CI, 0.43–0.89], P = 1.53 × 10−8). GRIA4 encodes an AMPA-sensitive glutamate receptor that mediates fast excitatory synaptic transmission and neuroplasticity. Conditional analyses revealed that the association was explained jointly by both traits. Enrichment analysis showed that the top risk genes and genes co-expressed with GRIA4 are enriched in cell adhesion, calcium ion binding, and synapses. They also have enriched expression in the brain and they have been implicated in the risk for other neuropsychiatric disorders. Further research is needed to determine the replicability of these findings and to identify the biological mechanisms through which genetic risk for each condition is conveyed.
Nanoporous aramid nanofibre separators for nonaqueous redox flow batteries
Authors: Tung Siu on , Fisher Sydney L. , Kotov Nicholas A. , Thompson Levi T. 
Published: October 2018

AbstractRedox flow batteries are attractive for large-scale energy storage due to a combination of high theoretical efficiencies and decoupled power and energy storage capacities. Efforts to significantly increase energy densities by using nonaqueous electrolytes have been impeded by separators with low selectivities. Here, we report nanoporous separators based on aramid nanofibres, which are assembled using a scalable, low cost, spin-assisted layer-by-layer technique. The multilayer structure yields 5 ± 0.5 nm pores, enabling nanofiltration with high selectivity. Further, surface modifications using polyelectrolytes result in enhanced performance. In vanadium acetylacetonate/acetonitrile-based electrolytes, the coated separator exhibits permeabilities an order of magnitude lower and ionic conductivities five times higher than those of a commercial separator. In addition, the coated separators exhibit exceptional stability, showing minimal degradation after more than 100 h of cycling. The low permeability translates into high coulombic efficiency in flow cell charge/discharge experiments performed at cycle times relevant for large-scale applications (5 h).
SIRT1 mediates obesity- and nutrient-dependent perturbation of pubertal timing by epigenetically controlling Kiss1 expression
Authors: Vazquez M. J. , Toro C. A. , Castellano J. M. , Ruiz-Pino F. , Roa J. , Beiroa D. , Heras V. , Velasco I. , Dieguez C. , Pinilla L. , Gaytan F. , Nogueiras R. , Bosch M. A. , Rønnekleiv O. K. , Lomniczi A. , Ojeda S. R. , Tena-Sempere M. 
Published: October 2018

AbstractPuberty is regulated by epigenetic mechanisms and is highly sensitive to metabolic and nutritional cues. However, the epigenetic pathways mediating the effects of nutrition and obesity on pubertal timing are unknown. Here, we identify Sirtuin 1 (SIRT1), a fuel-sensing deacetylase, as a molecule that restrains female puberty via epigenetic repression of the puberty-activating gene, Kiss1. SIRT1 is expressed in hypothalamic Kiss1 neurons and suppresses Kiss1 expression. SIRT1 interacts with the Polycomb silencing complex to decrease Kiss1 promoter activity. As puberty approaches, SIRT1 is evicted from the Kiss1 promoter facilitating a repressive-to-permissive switch in chromatin landscape. Early-onset overnutrition accelerates these changes, enhances Kiss1 expression and advances puberty. In contrast, undernutrition raises SIRT1 levels, protracts Kiss1 repression and delays puberty. This delay is mimicked by central pharmacological activation of SIRT1 or SIRT1 overexpression, achieved via transgenesis or virogenetic targeting to the ARC. Our results identify SIRT1-mediated inhibition of Kiss1 as key epigenetic mechanism by which nutritional cues and obesity influence mammalian puberty.
Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia
Authors: McMaster Mary L. , Berndt Sonja I. , Zhang Jianqing , Slager Susan L. , Li Shengchao Alfred , Vajdic Claire M. , Smedby Karin E. , Yan Huihuang , Birmann Brenda M. , Brown Elizabeth E. , Smith Alex , Kleinstern Geffen , Fansler Mervin M. , Mayr Christine , Zhu Bin , Chung Charles C. , Park Ju-Hyun , Burdette Laurie , Hicks Belynda D. , Hutchinson Amy , Teras Lauren R. , Adami Hans-Olov , Bracci Paige M. , McKay James , Monnereau Alain , Link Brian K. , Vermeulen Roel C. H. , Ansell Stephen M. , Maria Ann , Diver W. Ryan , Melbye Mads , Ojesina Akinyemi I. , Kraft Peter , Boffetta Paolo , Clavel Jacqueline , Giovannucci Edward , Besson Caroline M. , Canzian Federico , Travis Ruth C. , Vineis Paolo , Weiderpass Elisabete , Montalvan Rebecca , Wang Zhaoming , Yeager Meredith , Becker Nikolaus , Benavente Yolanda , Brennan Paul , Foretova Lenka , Maynadie Marc , Nieters Alexandra , de Sanjose Silvia , Staines Anthony , Conde Lucia , Riby Jacques , Glimelius Bengt , Hjalgrim Henrik , Pradhan Nisha , Feldman Andrew L. , Novak Anne J. , Lawrence Charles , Bassig Bryan A. , Lan Qing , Zheng Tongzhang , North Kari E. , Tinker Lesley F. , Cozen Wendy , Severson Richard K. , Hofmann Jonathan N. , Zhang Yawei , Jackson Rebecca D. , Morton Lindsay M. , Purdue Mark P. , Chatterjee Nilanjan , Offit Kenneth , Cerhan James R. , Chanock Stephen J. , Rothman Nathaniel , Vijai Joseph , Goldin Lynn R. , Skibola Christine F. , Caporaso Neil E. 
Published: October 2018

AbstractWaldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40–31.03, P = 1.36 × 10−54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45–6.96, P = 8.75 × 10−19). Both risk alleles are observed at a low frequency among controls (~2–3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.
Host-associated niche metabolism controls enteric infection through fine-tuning the regulation of type 3 secretion
Authors: Connolly James P. R. , Slater Sabrina L. , O’Boyle Nicky , Goldstone Robert J. , Crepin Valerie F. , Ruano-Gallego David , Herzyk Pawel , Smith David G. E. , Douce Gillian R. , Frankel Gad , Roe Andrew J. 
Published: October 2018

AbstractNiche-adaptation of a bacterial pathogen hinges on the ability to recognize the complexity of signals from the environment and integrate that information with the regulation of genes critical for infection. Here we report the transcriptome of the attaching and effacing pathogen Citrobacter rodentium during infection of its natural murine host. Pathogen gene expression in vivo was heavily biased towards the virulence factor repertoire and was found to be co-ordinated uniquely in response to the host. Concordantly, we identified the host-specific induction of a metabolic pathway that overlapped with the regulation of virulence. The essential type 3 secretion system and an associated suite of distinct effectors were found to be modulated co-ordinately through a unique mechanism involving metabolism of microbiota-derived 1,2-propanediol, which dictated the ability to colonize the host effectively. This study provides novel insights into how host-specific metabolic adaptation acts as a cue to fine-tune virulence.
Relativistic and resonant effects in the ionization of heavy atoms by ultra-intense hard X-rays
Authors: Rudek Benedikt , Toyota Koudai , Foucar Lutz , Erk Benjamin , Boll Rebecca , Bomme Cédric , Correa Jonathan , Carron Sebastian , Boutet Sébastien , Williams Garth J. , Ferguson Ken R. , Alonso-Mori Roberto , Koglin Jason E. , Gorkhover Tais , Bucher Maximilian , Lehmann Carl Stefan , Krässig Bertold , Southworth Stephen H. , Young Linda , Bostedt Christoph , Ueda Kiyoshi , Marchenko Tatiana , Simon Marc , Jurek Zoltan , Santra Robin , Rudenko Artem , Son Sang-Kil , Rolles Daniel 
Published: October 2018

AbstractAn accurate description of the interaction of intense hard X-ray pulses with heavy atoms, which is crucial for many applications of free-electron lasers, represents a hitherto unresolved challenge for theory because of the enormous number of electronic configurations and relativistic effects, which need to be taken into account. Here we report results on multiple ionization of xenon atoms by ultra-intense (about 1019 W/cm2) femtosecond X-ray pulses at photon energies from 5.5 to 8.3 keV and present a theoretical model capable of reproducing the experimental data in the entire energy range. Our analysis shows that the interplay of resonant and relativistic effects results in strongly structured charge state distributions, which reflect resonant positions of relativistically shifted electronic levels of highly charged ions created during the X-ray pulse. The theoretical approach described here provides a basis for accurate modeling of radiation damage in hard X-ray imaging experiments on targets with high-Z constituents.
Mucins trigger dispersal of Pseudomonas aeruginosa biofilms
Authors: Co Julia Y. , Cárcamo-Oyarce Gerardo , Billings Nicole , Wheeler Kelsey M. , Grindy Scott C. , Holten-Andersen Niels , Ribbeck Katharina 
Published: October 2018

AbstractMucus is a biological gel that lines all wet epithelia in the body, including the mouth, lungs, and digestive tract, and has evolved to protect the body from pathogenic infection. However, microbial pathogenesis is often studied in mucus-free environments that lack the geometric constraints and microbial interactions in physiological three-dimensional mucus gels. We developed fluid-flow and static test systems based on purified mucin polymers, the major gel-forming constituents of the mucus barrier, to understand how the mucus barrier influences bacterial virulence, particularly the integrity of Pseudomonas aeruginosa biofilms, which can become resistant to immune clearance and antimicrobial agents. We found that mucins separate the cells in P. aeruginosa biofilms and disperse them into suspension. Other viscous polymer solutions did not match the biofilm disruption caused by mucins, suggesting that mucin-specific properties mediate the phenomenon. Cellular dispersion depended on functional flagella, indicating a role for swimming motility. Taken together, our observations support a model in which host mucins are key players in the regulation of microbial virulence. These mucins should be considered in studies of mucosal pathogenesis and during the development of novel strategies to treat biofilms.
Fabrication of buried nanostructures by atomic layer deposition
Authors: Ali Rizwan , Saleem Muhammad Rizwan , Roussey Matthieu , Turunen Jari , Honkanen Seppo 
Published: October 2018

AbstractWe present a method for fabricating buried nanostructures by growing a dielectric cover layer on a corrugated surface profile by atomic layer deposition of TiO2. Selecting appropriate process parameters, the conformal growth of TiO2 results in a smooth, nearly flat-top surface of the structure. Such a hard surface can be easily cleaned without damage, making the nanostructure reusable after contamination. The technique has wide applicability in resonance-domain diffractive optics and in realization of quasi-planar metamaterials. We discuss design issues of such optical elements and demonstrate the method by fabricating narrow-band spectral filters based on the guided-mode resonance effect. These elements have strong potential for, e.g., sensing applications in harsh conditions.
Deciphering molecular details in the assembly of alpha-type carboxysome
Authors: Liu Yilan , He Xinyuan , Lim Weiping , Mueller Joshua , Lawrie Justin , Kramer Levi , Guo Jiantao , Niu Wei 
Published: October 2018

AbstractBacterial microcompartments (BMCs) are promising natural protein structures for applications that require the segregation of certain metabolic functions or molecular species in a defined microenvironment. To understand how endogenous cargos are packaged inside the protein shell is key for using BMCs as nano-scale reactors or delivery vesicles. In this report, we studied the encapsulation of RuBisCO into the α-type carboxysome from Halothiobacillus neapolitan. Our experimental data revealed that the CsoS2 scaffold proteins engage RuBisCO enzyme through an interaction with the small subunit (CbbS). In addition, the N domain of the large subunit (CbbL) of RuBisCO interacts with all shell proteins that can form the hexamers. The binding affinity between the N domain of CbbL and one of the major shell proteins, CsoS1C, is within the submicromolar range. The absence of the N domain also prevented the encapsulation of the rest of the RuBisCO subunits. Our findings complete the picture of how RuBisCOs are encapsulated into the α-type carboxysome and provide insights for future studies and engineering of carboxysome as a protein shell.
The impact of frequent napping and nap practice on sleep-dependent memory in humans
Authors: McDevitt Elizabeth A. , Sattari Negin , Duggan Katherine A. , Cellini Nicola , Whitehurst Lauren N. , Perera Chalani , Reihanabad Nicholas , Granados Samantha , Hernandez Lexus , Mednick Sara C. 
Published: October 2018

AbstractNapping benefits long-term memory formation and is a tool many individuals use to improve daytime functioning. Despite its potential advantages, approximately 47% of people in the United States eschew napping. The goal of this study was to determine whether people who endorse napping at least once a week (nap+) show differences in nap outcomes, including nap-dependent memory consolidation, compared with people who rarely or never nap (nap−). Additionally, we tested whether four weeks of nap practice or restriction would change sleep and performance profiles. Using a perceptual learning task, we found that napping enhanced performance to a greater degree in nap+ compared with nap− individuals (at baseline). Additionally, performance change was associated with different electrophysiological sleep features in each group. In the nap+ group, spindle density was positively correlated with performance improvement, an effect specific to spindles in the hemisphere contralateral to the trained visual field. In the nap− group, slow oscillatory power (0.5–1 Hz) was correlated with performance. Surprisingly, no changes to performance or brain activity during sleep emerged after four weeks of nap practice or restriction. These results suggest that individual differences may impact the potential benefits of napping on performance and the ability to become a better napper.
GOGO: An improved algorithm to measure the semantic similarity between gene ontology terms
Authors: Zhao Chenguang , Wang Zheng 
Published: October 2018

AbstractMeasuring the semantic similarity between Gene Ontology (GO) terms is an essential step in functional bioinformatics research. We implemented a software named GOGO for calculating the semantic similarity between GO terms. GOGO has the advantages of both information-content-based and hybrid methods, such as Resnik’s and Wang’s methods. Moreover, GOGO is relatively fast and does not need to calculate information content (IC) from a large gene annotation corpus but still has the advantage of using IC. This is achieved by considering the number of children nodes in the GO directed acyclic graphs when calculating the semantic contribution of an ancestor node giving to its descendent nodes. GOGO can calculate functional similarities between genes and then cluster genes based on their functional similarities. Evaluations performed on multiple pathways retrieved from the saccharomyces genome database (SGD) show that GOGO can accurately and robustly cluster genes based on functional similarities. We release GOGO as a web server and also as a stand-alone tool, which allows convenient execution of the tool for a small number of GO terms or integration of the tool into bioinformatics pipelines for large-scale calculations. GOGO can be freely accessed or downloaded from http://dna.cs.miami.edu/GOGO/.
Intravesical Mycobacterium brumae triggers both local and systemic immunotherapeutic responses against bladder cancer in mice
Authors: Noguera-Ortega Estela , Rabanal Rosa M. , Gómez-Mora Elisabet , Cabrera Cecilia , Luquin Marina , Julián Esther 
Published: October 2018

AbstractThe standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of liveMycobacterium bovisBCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such asMycobacterium brumae, and/or different vehicles for mycobacteria delivery, such as an olive oil (OO)-in-water emulsion. While it has been established that BCG treatment activates the immune system, the immune effects of altering the mycobacterium and/or the preparation remain unknown. In an orthotopic murine BC model, local immune responses were assessed by measuring immune cells into the bladder and macromolecules in the urine by flow cytometry and multiplexing, respectively. Systemic immune responses were analyzed by quantifying sera anti-mycobacteria antibody levels and recall responses ofex vivosplenocytes cultured with mycobacteria antigens. In both BCG- andM. brumae-treated mice, T, NK, and NKT cell infiltration in the bladder was significantly increased. Notably, T cell infiltration was enhanced in OO-in-water emulsified mycobacteria-treated mice, and urine IL-6 and KC concentrations were elevated. Furthermore, mycobacteria treatment augmented IgG antibody production and splenocyte proliferation, especially in mice receiving OO-in-water emulsified mycobacteria. Our data demonstrate that intravesical mycobacterial treatment triggers local and systemic immune responses, which are most significant when OO-in-water emulsified mycobacteria are used.
Inactive matrix Gla protein is a novel circulating biomarker predicting retinal arteriolar narrowing in humans
Authors: Wei Fang-Fei , Huang Qi-Fang , Zhang Zhen-Yu , Van Keer Karel , Thijs Lutgarde , Trenson Sander , Yang Wen-Yi , Cauwenberghs Nicholas , Mujaj Blerim , Kuznetsova Tatiana , Allegaert Karel , Struijker-Boudier Harry A. J. , Verhamme Peter , Vermeer Cees , Staessen Jan A. 
Published: October 2018

AbstractActive matrix Gla protein (MGP), a potent inhibitor of calcification in large arteries, protects against macrovascular complications. Recent studies suggested that active MGP helps maintaining the integrity of the renal and myocardial microcirculation, but its role in preserving the retinal microcirculation remains unknown. In 935 randomly recruited Flemish participants (mean age, 40.9 years; 50.3% women), we measured plasma desphospho-uncarboxylated MGP (dp–ucMGP), a marker of poor vitamin K status using an ELISA-based assay at baseline (1996–2010) and retinal microvascular diameters using IVAN software (Vasculomatic ala Nicola, version 1.1) including the central retinal arteriolar (CRAE) and venular (CRVE) equivalent and the arteriole-to-venule ratio (AVR) at follow-up (2008–2015). CRAE (P = 0.005) and AVR (P = 0.080) at follow-up decreased across tertiles of the dp–ucMGP distribution. In unadjusted models, for a doubling of dp–ucMGP at baseline, CRAE and AVR at follow-up respectively decreased by 1.40 µm (95% confidence interval [CI], 0.32 to 2.48; P = 0.011) and 0.006 (CI, 0.001 to 0.011; P = 0.016). In multivariable-adjusted models accounting for sex, baseline characteristics and follow-up duration, these estimates were −1.03 µm (CI, −1.96 to −0.11; P = 0.028) and −0.007 (CI, −0.011 to −0.002; P = 0.007). Additional adjustment for changes from baseline to follow-up in major baseline characteristics yielded as estimates −0.91 µm (CI, −1.82 to −0.01; P = 0.048) and −0.006 (95% CI, −0.011 to −0.001; P = 0.014), respectively. Circulating inactive dp–ucMGP is a long-term predictor of smaller retinal arteriolar diameter in the general population. Our observations highlight the possibility that vitamin K supplementation might promote retinal health.
Uni- and triaxial accelerometric signals agree during daily routine, but show differences between sports
Authors: Smith Maia P. , Horsch Alexander , Standl Marie , Heinrich Joachim , Schulz Holger 
Published: October 2018

AbstractAccelerometers objectively monitor physical activity, and ongoing research suggests they can also detect patterns of body movement. However, different types of signal (uniaxial, captured by older studies, vs. the newer triaxial) and or/device (validated Actigraph used by older studies, vs. others) may lead to incomparability of results from different time periods. Standardization is desirable. We establish whether uniaxial signals adequately monitor routine activity, and whether triaxial accelerometry can detect sport-specific variations in movement pattern. 1402 adolescents wore triaxial Actigraphs (GT3X) for one week and diaried sport. Uni- and triaxial counts per minute were compared across the week and between over 30 different sports. Across the whole recording period 95% of variance in triaxial counts was explained by the vertical axis (5th percentile for R2, 91%). Sport made up a small fraction of daily routine, but differences were visible: even when total acceleration was comparable, little was vertical in horizontal movements, such as ice skating (uniaxial counts 41% of triaxial) compared to complex movements (taekwondo, 55%) or ambulation (soccer, 69%). Triaxial accelerometry captured differences in movement pattern between sports, but so little time was spent in sport that, across the whole day, uni- and triaxial signals correlated closely. This indicates that, with certain limitations, uniaxial accelerometric measures of routine activity from older studies can be feasibly compared to triaxial measures from newer studies. Comparison of new studies based on raw accelerations to older studies based on proprietary devices and measures (epochs, counts) will require additional efforts which are not addressed in this paper.