bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21
Authors: Ostrom Quinn T. , Kinnersley Ben , Wrensch Margaret R. , Eckel-Passow Jeanette E. , Armstrong Georgina , Rice Terri , Chen Yanwen , Wiencke John K. , McCoy Lucie S. , Hansen Helen M. , Amos Christopher I. , Bernstein Jonine L. , Claus Elizabeth B. , Il’yasova Dora , Johansen Christoffer , Lachance Daniel H. , Lai Rose K. , Merrell Ryan T. , Olson Sara H. , Sadetzki Siegal , Schildkraut Joellen M. , Shete Sanjay , Rubin Joshua B. , Lathia Justin D. , Berens Michael E. , Andersson Ulrika , Rajaraman Preetha , Chanock Stephen J. , Linet Martha S. , Wang Zhaoming , Yeager Meredith ,   GliomaScan consortium, Beane Freeman Laura E. , Koutros Stella , Albanes Demetrius , Visvanathan Kala , Stevens Victoria L. , Henriksson Roger , Michaud Dominique S. , Feychting Maria , Ahlbom Anders , Giles Graham G. , Milne Roger , McKean-Cowdin Roberta , Le Marchand Loic , Stampfer Meir , Ruder Avima M. , Carreon Tania , Hallmans Göran , Zeleniuch-Jacquotte Anne , Gaziano J. Michael , Sesso Howard D. , Purdue Mark P. , White Emily , Peters Ulrike , Buring Julie , Houlston Richard S. , Jenkins Robert B. , Melin Beatrice , Bondy Melissa L. , Barnholtz-Sloan Jill. S. 
Published: May 2018

AbstractIncidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
Trafficking, localization and degradation of the Na+,HCO3− co-transporter NBCn1 in kidney and breast epithelial cells
Authors: Olesen Christina Wilkens , Vogensen Jens , Axholm Ida , Severin Marc , Schnipper Julie , Pedersen Isabella Skandorff , von Stemann Jakob Hjorth , Schrøder Jacob Morville , Christensen Dan Ploug , Pedersen Stine Falsig 
Published: May 2018

AbstractThe Na+;HCO3− co-transporter NBCn1 (SLC4A7) is a major regulator of intracellular pH yet its trafficking and turnover are essentially unstudied. Here, we used MDCK-II and MCF-7 cells to investigate these processes in epithelial cells. GFP-NBCn1 membrane localization was abolished by truncation of the full NBCn1 C-terminal tail (C-tail) yet did not require the C-terminal PDZ-binding motif (ETSL). Glutathione-S-Transferase-pulldown of the C-tail followed by mass spectrometry analysis revealed putative interactions with multiple sorting-, degradation- and retention factors, including the scaffolding protein RACK1. Pulldown of FLAG-tagged deletion constructs mapped the RACK1 interaction to the proximal NBCn1 C-tail. Proximity Ligation Assay and co-immunoprecipitation confirmed that native NBCn1 interacts with RACK1 in a cellular context. Consistent with a functional role of this complex, RACK1 knockdown reduced NBCn1 membrane localization without affecting total NBCn1 expression. Notably, only non-confluent cells exhibited detectable NBCn1-RACK1 plasma membrane co-localization, suggesting that RACK1 regulates the trafficking of NBCn1 to the membrane. Whereas total NBCn1 degradation was slow, with a half-life of more than 24 h, one-third of surface NBCn1 was constitutively endocytosed from the basolateral membrane within 60 min. This suggests that a fraction of NBCn1 exhibits recycling between the basolateral membrane and intracellular compartment(s). Our findings have important implications for understanding NBCn1 regulation as well as its dysregulation in disease.
Unexpected infection outcomes of China-origin H7N9 low pathogenicity avian influenza virus in turkeys
Authors: Slomka Marek J. , Seekings Amanda H. , Mahmood Sahar , Thomas Saumya , Puranik Anita , Watson Samantha , Byrne Alexander M. P. , Hicks Daniel , Nunez Alejandro , Brown Ian H. , Brookes Sharon M. 
Published: May 2018

AbstractThe China-origin H7N9 low pathogenicity avian influenza virus (LPAIV) emerged as a zoonotic threat in 2013 where it continues to circulate in live poultry markets. Absence of overt clinical signs in poultry is a typical LPAIV infection outcome, and has contributed to its insidious maintenance in China. This study is the first description of H7N9 LPAIV (A/Anhui/1/13) infection in turkeys, with efficient transmission to two additional rounds of introduced contact turkeys which all became infected during cohousing. Surprisingly, mortality was observed in six of eight (75%) second-round contact turkeys which is unusual for LPAIV infection, with unexpected systemic dissemination to many organs beyond the respiratory and enteric tracts, but interestingly no accompanying mutation to highly pathogenic AIV. The intravenous pathogenicity index score for a turkey-derived isolate (0.39) affirmed the LPAIV phenotype. However, the amino acid change L235Q in the haemagglutinin gene occurred in directly-infected turkeys and transmitted to the contacts, including those that died and the two which resolved infection to survive to the end of the study. This polymorphism was indicative of a reversion from mammalian to avian adaptation for the H7N9 virus. This study underlined a new risk to poultry in the event of H7N9 spread beyond China.
Salivary levels of total huntingtin are elevated in Huntington’s disease patients
Authors: Corey-Bloom Jody , Haque Ameera S. , Park Sungmee , Nathan Ajay S. , Baker Robert W. , Thomas Elizabeth A. 
Published: May 2018

AbstractPatients with Huntington’s disease (HD), an autosomal-dominant neurodegenerative disease, show substantial variability in age-of-onset, symptom severity and course of illness, warranting the need for biomarkers to anticipate and monitor these features. The HD gene encodes the disease protein huntingtin (Htt), a potentially useful biomarker for this disease. In the current study, we determined whether total Htt protein (normal plus mutant; “tHtt”) could be reliably measured in human saliva, a body fluid that is much more accessible compared to cerebral spinal fluid or even blood, and whether salivary levels of tHtt were clinically meaningful. We collected 146 saliva samples from manifest HD patients, early-premanifest individuals, late-premanifest patients, gene-negative family members and normal controls. We found that tHtt protein could be reliably and stably detected in human saliva and that tHtt levels were significantly increased in saliva from HD individuals compared to normal controls. Salivary tHtt showed no gender effects, nor were levels correlated with total protein levels in saliva. Salivary tHtt was significantly positively correlated with age, but not age-of-onset or CAG-repeat length. Importantly, salivary tHtt was significantly correlated with several clinical measures, indicating relevance to disease symptom onset and/or severity. Measurements of salivary tHtt offer significant promise as a relevant, non-invasive disease biomarker for HD, and its use could be implemented into clinical applications.
Three-dimensional hot electron photovoltaic device with vertically aligned TiO2 nanotubes
Authors: Goddeti Kalyan C. , Lee Changhwan , Lee Young Keun , Park Jeong Young 
Published: May 2018

AbstractTitanium dioxide (TiO2) nanotubes with vertically aligned array structures show substantial advantages in solar cells as an electron transport material that offers a large surface area where charges travel linearly along the nanotubes. Integrating this one-dimensional semiconductor material with plasmonic metals to create a three-dimensional plasmonic nanodiode can influence solar energy conversion by utilizing the generated hot electrons. Here, we devised plasmonic Au/TiO2 and Ag/TiO2 nanodiode architectures composed of TiO2 nanotube arrays for enhanced photon absorption, and for the subsequent generation and capture of hot carriers. The photocurrents and incident photon to current conversion efficiencies (IPCE) were obtained as a function of photon energy for hot electron detection. We observed enhanced photocurrents and IPCE using the Ag/TiO2 nanodiode. The strong plasmonic peaks of the Au and Ag from the IPCE clearly indicate an enhancement of the hot electron flux resulting from the presence of surface plasmons. The calculated electric fields and the corresponding absorbances of the nanodiode using finite-difference time-domain simulation methods are also in good agreement with the experimental results. These results show a unique strategy of combining a hot electron photovoltaic device with a three-dimensional architecture, which has the clear advantages of maximizing light absorption and a metal–semiconductor interface area.
Amino acid compositions contribute to the proteins’ evolution under the influence of their abundances and genomic GC content
Authors: Du Meng-Ze , Liu Shuo , Zeng Zhi , Alemayehu Labena Abraham , Wei Wen , Guo Feng-Biao 
Published: May 2018

AbstractInconsistent results on the association between evolutionary rates and amino acid composition of proteins have been reported in eukaryotes. However, there are few studies of how amino acid composition can influence evolutionary rates in bacteria. Thus, we constructed linear regression models between composition frequencies of amino acids and evolutionary rates for bacteria. Compositions of all amino acids can on average explain 21.5% of the variation in evolutionary rates among 273 investigated bacterial organisms. In five model organisms, amino acid composition contributes more to variation in evolutionary rates than protein abundance, and frequency of optimal codons. The contribution of individual amino acid composition to evolutionary rate varies among organisms. The closer the GC-content of genome to its maximum or minimum, the better the correlation between the amino acid content and the evolutionary rate of proteins would appear in that genome. The types of amino acids that significantly contribute to evolutionary rates can be grouped into GC-rich and AT-rich amino acids. Besides, the amino acid with high composition also contributes more to evolutionary rates than amino acid with low composition in proteome. In summary, amino acid composition significantly contributes to the rate of evolution in bacterial organisms and this in turn is impacted by GC-content.
Genome-wide prediction of CRISPR/Cas9 targets in Kluyveromyces marxianus and its application to obtain a stable haploid strain
Authors: Lee Ming-Hsuan , Lin Jinn-Jy , Lin Yu-Ju , Chang Jui-Jen , Ke Huei-Mien , Fan Wen-Lang , Wang Tzi-Yuan , Li Wen-Hsiung 
Published: May 2018

AbstractKluyveromyces marxianus, a probiotic yeast, is important in industrial applications because it has a broad substrate spectrum, a rapid growth rate and high thermotolerance. To date, however, there has been little effort in its genetic engineering by the CRISPR/Cas9 system. Therefore, we aimed at establishing the CRISPR/Cas9 system inK. marxianusand creating stable haploid strains, which will make genome engineering simpler. First, we predicted the genome-wide target sites of CRISPR/Cas9 that have been conserved among the eight sequenced genomes ofK. marxianusstrains. Second, we established the CRISPR/Cas9 system in theK. marxianus4G5 strain, which was selected for its high thermotolerance, rapid growth, a pH range of pH3-9, utilization of xylose, cellobiose and glycerol, and toxin tolerance, and we knocked out its MATα3 to prevent mating-type switching. Finally, we usedK. marxianusMATα3 knockout diploid strains to obtain stable haploid strains with a growth rate comparable to that of the diploid 4G5 strain. In summary, we present the workflow from identifying conserved CRISPR/Cas9 targets in the genome to knock out the MATα3 genes inK. marxianusto obtain a stable haploid strain, which can facilitate genome engineering applications.
Functional expression of an oxygen-labile nitrogenase in an oxygenic photosynthetic organism
Authors: Tsujimoto Ryoma , Kotani Hiroya , Yokomizo Konomi , Yamakawa Hisanori , Nonaka Aoi , Fujita Yuichi 
Published: May 2018

AbstractTransfer of nitrogen fixation ability to plants, especially crops, is a promising approach to mitigate dependence on chemical nitrogen fertilizer and alleviate environmental pollution caused by nitrogen fertilizer run-off. However, the need to transfer a large number of nitrogen fixation (nif) genes and the extreme vulnerability of nitrogenase to oxygen constitute major obstacles for transfer of nitrogen-fixing ability to plants. Here we demonstrate functional expression of a cyanobacterial nitrogenase in the non-diazotrophic cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis 6803). A 20.8-kb chromosomal fragment containing 25 nif and nif-related genes of the diazotrophic cyanobacterium Leptolyngbya boryana was integrated into a neutral genome site of Synechocystis 6803 by five-step homologous recombination together with the cnfR gene encoding the transcriptional activator of the nif genes to isolate CN1. In addition, two other transformants CN2 and CN3 carrying additional one and four genes, respectively, were isolated from CN1. Low but significant nitrogenase activity was detected in all transformants. This is the first example of nitrogenase activity detected in non-diazotrophic photosynthetic organisms. These strains provide valuable platforms to investigate unknown factors that enable nitrogen-fixing growth of non-diazotrophic photosynthetic organisms, including plants.
Recruitment Drives Spatial Variation in Recovery Rates of Resilient Coral Reefs
Authors: Holbrook Sally J. , Adam Thomas C. , Edmunds Peter J. , Schmitt Russell J. , Carpenter Robert C. , Brooks Andrew J. , Lenihan Hunter S. , Briggs Cheryl J. 
Published: May 2018

AbstractTropical reefs often undergo acute disturbances that result in landscape-scale loss of coral. Due to increasing threats to coral reefs from climate change and anthropogenic perturbations, it is critical to understand mechanisms that drive recovery of these ecosystems. We explored this issue on the fore reef of Moorea, French Polynesia, following a crown-of-thorns seastar outbreak and cyclone that dramatically reduced cover of coral. During the five-years following the disturbances, the rate of re-establishment of coral cover differed systematically around the triangular-shaped island; coral cover returned most rapidly at sites where the least amount of live coral remained after the disturbances. Although sites differed greatly in the rate of return of coral, all showed at least some evidence of re-assembly to their pre-disturbance community structure in terms of relative abundance of coral taxa and other benthic space holders. The primary driver of spatial variation in recovery was recruitment of sexually-produced corals; subsequent growth and survivorship were less important in shaping the spatial pattern. Our findings suggest that, although the coral community has been resilient, some areas are unlikely to attain the coral cover and taxonomic structure they had prior to the most recent disturbances before the advent of another landscape-scale perturbation.
Role of IGF-1R in ameliorating apoptosis of GNE deficient cells
Authors: Singh Reema , Chaudhary Priyanka , Arya Ranjana 
Published: May 2018

AbstractSialic acids (SAs) are nine carbon acidic amino sugars, found at the outermost termini of glycoconjugates performing various physiological and pathological functions. SA synthesis is regulated by UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) that catalyzes rate limiting steps. Mutations in GNE result in rare genetic disorders, GNE myopathy and Sialuria. Recent studies indicate an alternate role of GNE in cell apoptosis and adhesion, besides SA biosynthesis. In the present study, using a HEK cell-based model for GNE myopathy, the role of Insulin-like Growth Factor Receptor (IGF-1R) as cell survival receptor protein was studied to counter the apoptotic effect of non-functional GNE. In the absence of functional GNE, IGF-1R was hyposialylated and transduced a downstream signal upon IGF-1 (IGF-1R ligand) treatment. IGF-1 induced activation of IGF-1R led to AKT (Protein Kinase B) phosphorylation that may phosphorylate BAD (BCL2 Associated Death Promoter) and its dissociation from BCL2 to prevent apoptosis. However, reduced ERK (Extracellular signal-regulated kinases) phosphorylation in GNE deficient cells after IGF-1 treatment suggests downregulation of the ERK pathway. A balance between the ERK and AKT pathways may determine the cell fate towards survival or apoptosis. Our study suggests that IGF-1R activation may rescue apoptotic cell death of GNE deficient cell lines and has potential as therapeutic target.
A generalised significance test for individual communities in networks
Authors: Kojaku Sadamori , Masuda Naoki 
Published: May 2018

AbstractMany empirical networks have community structure, in which nodes are densely interconnected within each community (i.e., a group of nodes) and sparsely across different communities. Like other local and meso-scale structure of networks, communities are generally heterogeneous in various aspects such as the size, density of edges, connectivity to other communities and significance. In the present study, we propose a method to statistically test the significance of individual communities in a given network. Compared to the previous methods, the present algorithm is unique in that it accepts different community-detection algorithms and the corresponding quality function for single communities. The present method requires that a quality of each community can be quantified and that community detection is performed as optimisation of such a quality function summed over the communities. Various community detection algorithms including modularity maximisation and graph partitioning meet this criterion. Our method estimates a distribution of the quality function for randomised networks to calculate a likelihood of each community in the given network. We illustrate our algorithm by synthetic and empirical networks.
A Phase I Clinical Trial with Ex Vivo Expanded Recipient Regulatory T cells in Living Donor Kidney Transplants
Authors: Mathew James M. , H.-Voss Jessica , LeFever Ann , Konieczna Iwona , Stratton Cheryl , He Jie , Huang Xuemei , Gallon Lorenzo , Skaro Anton , Ansari Mohammed Javeed , Leventhal Joseph R. 
Published: May 2018

AbstractThere is considerable interest in therapeutic transfer of regulatory T cells (Tregs) for controlling aberrant immune responses. Initial clinical trials have shown the safety of Tregs in hematopoietic stem cell transplant recipients and subjects with juvenile diabetes. Our hypothesis is that infusion(s) of Tregs may induce transplant tolerance thus avoiding long-term use of toxic immunosuppressive agents that cause increased morbidity/mortality. Towards testing our hypothesis, we conducted a phase I dose escalation safety trial infusing billions ofex vivoexpanded recipient polyclonal Tregs into living donor kidney transplant recipients. Despite variability in recipient’s renal disease, our expansion protocol produced Tregs which met all release criteria, expressing >98% CD4+CD25+with <1% CD8+and CD19+contamination. Our product displayed >80% FOXP3 expression with stable demethylation in the FOXP3 promoter. Functionally, expanded Tregs potently suppressed allogeneic responses and induced the generation of new Tregs in the recipient’s allo-respondersin vitro. Within recipients, expanded Tregs amplified circulating Treg levels in a sustained manner. Clinically, all doses of Treg therapy tested were safe with no adverse infusion related side effects, infections or rejection events up to two years post-transplant. This study provides the necessary safety data to advance Treg cell therapy to phase II efficacy trials.
Daytime eyeshine contributes to pupil camouflage in a cryptobenthic marine fish
Authors: Santon Matteo , Bitton Pierre-Paul , Harant Ulrike K. , Michiels Nico K. 
Published: May 2018

AbstractOcular reflectors enhance eye sensitivity in dim light, but can produce reflected eyeshine when illuminated. Some fish can occlude their reflectors during the day. The opposite is observed in cryptic sit-and-wait predators such as scorpionfish and toadfish, where reflectors are occluded at night and exposed during the day. This results in daytime eyeshine, proposed to enhance pupil camouflage by reducing the contrast between the otherwise dark pupil and the surrounding tissue. In this study, we test this hypothesis in the scorpionfishScorpaena porcusand show that eyeshine is the result of two mechanisms: the previously describedStratum Argenteum Reflected(SAR) eyeshine, andPigment Epithelium Transmitted(PET) eyeshine, a newly described mechanism for this species. We confirm that the ocular reflector is exposed only when the eye is light-adapted, and present field measurements to show that eyeshine reduces pupil contrast against the iris. We then estimate the relative contribution of SAR and PET eyeshine to pupil brightness. Visual models for different light scenarios in the field show that daytime eyeshine enhances pupil camouflage from the perspective of a prey fish. We propose that the reversed occlusion mechanism of some cryptobenthic predators has evolved as a compromise between camouflage and vision.
Transcriptomic integration of D4R and MOR signaling in the rat caudate putamen
Authors: Valderrama-Carvajal Alejandra , Irizar Haritz , Gago Belén , Jiménez-Urbieta Haritz , Fuxe Kjell , Rodríguez-Oroz María C. , Otaegui David , Rivera Alicia 
Published: May 2018

AbstractMorphine binding to opioid receptors, mainly to μ opioid receptor (MOR), induces alterations in intracellular pathways essential to the initial development of addiction. The activation of the dopamine D4 receptor (D4R), which is expressed in the caudate putamen (CPu), mainly counteracts morphine-induced alterations in several molecular networks. These involve transcription factors, adaptive changes of MOR signaling, activation of the nigrostriatal dopamine pathway and behavioural effects, underlining functional D4R/MOR interactions. To shed light on the molecular mechanisms implicated, we evaluated the transcriptome alterations following acute administration of morphine and/or PD168,077 (D4R agonist) using whole-genome microarrays and a linear regression-based differential expression analysis. The results highlight the development of a unique transcriptional signature following the co-administration of both drugs that reflects a countereffect of PD168,077 on morphine effects. A KEGG pathway enrichment analysis using GSEA identified 3 pathways enriched positively in morphine vs control and negatively in morphine + PD168,077 vs morphine (Ribosome, Complement and Coagulation Cascades, Systemic Lupus Erythematosus) and 3 pathways with the opposite enrichment pattern (Alzheimer’s Disease, Neuroactive Ligand Receptor Interaction, Oxidative Phosphorilation). This work supports the massive D4R/MOR functional integration at the CPu and provides a gateway to further studies on the use of D4R drugs to modulate morphine-induced effects.