bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engaging Women: Addressing the Gender Gap in Women’s Networking and Productivity
Authors: Barnes Tiffany D. , Beaulieu Emily 
Published: March 2017

ABSTRACT
Women earn 40% of new PhDs in political science; however, once they enter the profession, they have strikingly different experiences than their male counterparts—particularly in the small but influential field of political methodology. For several years, the Society for Political Methodology, with support from the National Science Foundation, has attempted to address this gender gap through the Visions in Methodology (VIM) program. VIM features an annual conference that brings women together to present and discuss their research and to participate in professional-development sessions. Do programs like VIM have the desired impact? Using an original survey of political scientists, this study provides insights into the ways that bringing women together in small-group settings like VIM might facilitate networking and enhance productivity. In particular, the study finds that women who attend the VIM conference are better networked and more productive in terms of publication.
IL-15 sustains IL-7R-independent ILC2 and ILC3 development
Authors: Robinette Michelle L. , Bando Jennifer K. , Song Wilbur , Ulland Tyler K. , Gilfillan Susan , Colonna Marco 
Published: March 2017

AbstractThe signals that maintain tissue-resident innate lymphoid cells (ILC) in different microenvironments are incompletely understood. Here we show that IL-7 receptor (IL-7R) is not strictly required for the development of any ILC subset, as residual cells persist in the small intestinal lamina propria (siLP) of adult and neonatal Il7ra−/− mice. Il7ra−/− ILC2 primarily express an ST2− phenotype, but are not inflammatory ILC2. CCR6+ ILC3, which express higher Bcl-2 than other ILC3, are the most abundant subset in Il7ra−/− siLP. All ILC subsets are functionally competent in vitro, and are sufficient to provide enhanced protection to infection with C. rodentium. IL-15 equally sustains wild-type and Il7ra−/− ILC survival in vitro and compensates for IL-7R deficiency, as residual ILCs are depleted in mice lacking both molecules. Collectively, these data demonstrate that siLP ILCs are not completely IL-7R dependent, but can persist partially through IL-15 signalling.
USP9X regulates centrosome duplication and promotes breast carcinogenesis
Authors: Li Xin , Song Nan , Liu Ling , Liu Xinhua , Ding Xiang , Song Xin , Yang Shangda , Shan Lin , Zhou Xing , Su Dongxue , Wang Yue , Zhang Qi , Cao Cheng , Ma Shuai , Yu Na , Yang Fuquan , Wang Yan , Yao Zhi , Shang Yongfeng , Shi Lei 
Published: March 2017

AbstractDefective centrosome duplication is implicated in microcephaly and primordial dwarfism as well as various ciliopathies and cancers. Yet, how the centrosome biogenesis is regulated remains poorly understood. Here we report that the X-linked deubiquitinase USP9X is physically associated with centriolar satellite protein CEP131, thereby stabilizing CEP131 through its deubiquitinase activity. We demonstrate that USP9X is an integral component of centrosome and is required for centrosome biogenesis. Loss-of-function of USP9X impairs centrosome duplication and gain-of-function of USP9X promotes centrosome amplification and chromosome instability. Significantly, USP9X is overexpressed in breast carcinomas, and its level of expression is correlated with that of CEP131 and higher histologic grades of breast cancer. Indeed, USP9X, through regulation of CEP131 abundance, promotes breast carcinogenesis. Our experiments identify USP9X as an important regulator of centrosome biogenesis and uncover a critical role for USP9X/CEP131 in breast carcinogenesis, supporting the pursuit of USP9X/CEP131 as potential targets for breast cancer intervention.
Low-level laser facilitates alternatively activated macrophage/microglia polarization and promotes functional recovery after crush spinal cord injury in rats
Authors: Song Ji Wei , Li Kun , Liang Zhuo Wen , Dai Chen , Shen Xue Feng , Gong Yu Ze , Wang Shuang , Hu Xue Yu , Wang Zhe 
Published: March 2017

AbstractMacrophages and resident microglia play an import role in the secondary neuroinflammation response following spinal cord injury. Reprogramming of macrophage/microglia polarization is an import strategy for spinal cord injury restoration. Low-level laser therapy (LLLT) is a noninvasive treatment that has been widely used in neurotrauma and neurodegenerative diseases. However, the influence of low-level laser on polarization of macrophage/microglia following spinal cord injury remains unknown. The present study applied low-level laser therapy on a crush spinal cord injury rat model. Using immunofluorescence, flow cytometry, RT-qPCR, and western blot assays, we found that low-level laser therapy altered the polarization state to a M2 tendency. A greater number of neurons survived in the pare injury site, which was accompanied by higher BBB scores in the LLLT group. Furthermore, low-level laser therapy elevated expression of interleukin 4 (IL-4) and interleukin 13 (IL-13). Results from this study show that low-level laser therapy has the potential for reducing inflammation, regulating macrophage/microglia polarization, and promoting neuronal survival. These beneficial effects demonstrate that low-level laser therapy may be an effective candidate for clinical treatment of spinal cord injury.
Problems with visual statistical learning in developmental dyslexia
Authors: Sigurdardottir Heida Maria , Danielsdottir Hilda Bjork , Gudmundsdottir Margret , Hjartarson Kristjan Helgi , Thorarinsdottir Elin Astros , Kristjánsson Árni 
Published: March 2017

AbstractPrevious research shows that dyslexic readers are impaired in their recognition of faces and other complex objects, and show hypoactivation in ventral visual stream regions that support word and object recognition. Responses of these brain regions are shaped by visual statistical learning. If such learning is compromised, people should be less sensitive to statistically likely feature combinations in words and other objects, and impaired visual word and object recognition should be expected. We therefore tested whether people with dyslexia showed diminished capability for visual statistical learning. Matched dyslexic and typical readers participated in tests of visual statistical learning of pairs of novel shapes that frequently appeared together. Dyslexic readers on average recognized fewer pairs than typical readers, indicating some problems with visual statistical learning. These group differences were not accounted for by differences in intelligence, ability to remember individual shapes, or spatial attention paid to the stimuli, but other attentional problems could play a mediating role. Deficiencies in visual statistical learning may in some cases prevent appropriate experience-driven shaping of neuronal responses in the ventral visual stream, hampering visual word and object recognition.
Quantitative chromatin proteomics reveals a dynamic histone post-translational modification landscape that defines asexual and sexual Plasmodium falciparum parasites
Authors: Coetzee Nanika , Sidoli Simone , van Biljon Riëtte , Painter Heather , Llinás Manuel , Garcia Benjamin A. , Birkholtz Lyn-Marie 
Published: March 2017

AbstractGene expression in Plasmodia integrates post-transcriptional regulation with epigenetic marking of active genomic regions through histone post-translational modifications (PTMs). To generate insights into the importance of histone PTMs to the entire asexual and sexual developmental cycles of the parasite, we used complementary and comparative quantitative chromatin proteomics to identify and functionally characterise histone PTMs in 8 distinct life cycle stages of P. falciparum parasites. ~500 individual histone PTMs were identified of which 106 could be stringently validated. 46 individual histone PTMs and 30 co-existing PTMs were fully quantified with high confidence. Importantly, 15 of these histone PTMs are novel for Plasmodia (e.g. H3K122ac, H3K27me3, H3K56me3). The comparative nature of the data revealed a highly dynamic histone PTM landscape during life cycle development, with a set of histone PTMs (H3K4ac, H3K9me1 and H3K36me2) displaying a unique and conserved abundance profile exclusively during gametocytogenesis (P < 0.001). Euchromatic histone PTMs are abundant during schizogony and late gametocytes; heterochromatic PTMs mark early gametocytes. Collectively, this data provides the most accurate, complete and comparative chromatin proteomic analyses of the entire life cycle development of malaria parasites. A substantial association between histone PTMs and stage-specific transition provides insights into the intricacies characterising Plasmodial developmental biology.
Discovery and characterization of verinurad, a potent and specific inhibitor of URAT1 for the treatment of hyperuricemia and gout
Authors: Tan Philip K. , Liu Sha , Gunic Esmir , Miner Jeffrey N. 
Published: March 2017

AbstractGout is caused by elevated serum urate levels, which can be treated using inhibitors of the uric acid transporter, URAT1. Here, we characterize verinurad (RDEA3170), which is currently under evaluation for gout therapy. Verinurad specifically inhibits URAT1 with a potency of 25 nM. High affinity inhibition of uric acid transport requires URAT1 residues Cys-32, Ser-35, Phe-365 and Ile-481. Unlike other available uricosuric agents, the requirement for Cys-32 is unique to verinurad. Two of these residues, Ser-35 and Phe-365, are also important for urate transport kinetics. A URAT1 binding assay using radiolabeled verinurad revealed that distinct URAT1 inhibitors benzbromarone, sulfinpyrazone and probenecid all inhibit verinurad binding via a competitive mechanism. However, mutations made within the predicted transporter substrate channel differentially altered the potency for individual URAT1 inhibitors. Overall, our results suggest that URAT1 inhibitors bind to a common site in the core of the transporter and sterically hinder the transit of uric acid through the substrate channel, albeit with vastly different potencies and with differential interactions with specific URAT1 amino acids.
TGFBI Gene Mutation Analysis of Clinically Diagnosed Granular Corneal Dystrophy Patients Prior to PTK: A Pilot Study from Eastern China
Authors: Zeng Li , Zhao Jing , Chen Yingjun , Zhao Feng , Li Meiyan , Chao-Shern Connie , Moore Tara , Marshall John , Zhou Xingtao 
Published: March 2017

AbstractThis study investigated the TGFBI gene mutation types in outpatients clinically diagnosed with granular corneal dystrophy (GCD) prior to phototherapeutic keratectomy (PTK), also calculated the mutation rate of subjects with normal corneas, but positive family history. Clinical GCD outpatients and consanguineous family members were enrolled in this study. Among total 42 subjects: 24 patients from 23 unrelated families had typical signs of GCD on corneas; 5 patients from 5 unrelated families had atypical signs; 13 subjects from 11 unrelated families had no corneal signs but positive family history. Using Avellino gene test kit, the TGFBI mutation detection was performed on DNA samples from all subjects. 36 subjects were detected to carry heterozygous TGFBI gene mutations. Among 24 clinical GCD patients, the proportion of R124H, R555Q, R124L, R555W and R124C were 37.5%, 16.7%, 25.0%, 20.8% and 0%, respectively, and 2 patients had been diagnosed with GCD according to the opacities thriving after LASIK (R124H) and PRK (R555W). The mutation rate of 13 subjects having no signs but positive family history was 69.2%. R124H mutation is the most prominent mutation type among GCD outpatients in Eastern China. It is recommended to conduct gene detection for patients with positive family history prior to refractive surgeries.
Alterations in erythrocyte fatty acid composition in preclinical Alzheimer’s disease
Authors: Goozee Kathryn , Chatterjee Pratishtha , James Ian , Shen Kaikai , Sohrabi Hamid R. , Asih Prita R. , Dave Preeti , Ball Bethany , ManYan Candice , Taddei Kevin , Chung Roger , Garg Manohar L. , Martins Ralph N. 
Published: March 2017

AbstractBrain and blood fatty acids (FA) are altered in Alzheimer’s disease and cognitively impaired individuals, however, FA alterations in the preclinical phase, prior to cognitive impairment have not been investigated previously. The current study therefore evaluated erythrocyte FA in cognitively normal elderly participants aged 65–90 years via trans-methylation followed by gas chromatography. The neocortical beta-amyloid load (NAL) measured via positron emission tomography (PET) using ligand 18F-Florbetaben, was employed to categorise participants as low NAL (standard uptake value ratio; SUVR < 1.35, N = 65) and high NAL or preclinical AD (SUVR ≥ 1.35, N = 35) wherein, linear models were employed to compare FA compositions between the two groups. Increased arachidonic acid (AA, p < 0.05) and decreased docosapentaenoic acid (DPA, p < 0.05) were observed in high NAL. To differentiate low from high NAL, the area under the curve (AUC) generated from a ‘base model’ comprising age, gender, APOEε4 and education (AUC = 0.794) was outperformed by base model + AA:DPA (AUC = 0.836). Our findings suggest that specific alterations in erythrocyte FA composition occur very early in the disease pathogenic trajectory, prior to cognitive impairment. As erythrocyte FA levels are reflective of tissue FA, these alterations may provide insight into the pathogenic mechanism(s) of the disease and may highlight potential early diagnostic markers and therapeutic targets.
The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells
Authors: Schuster Manuel , Schnell Leonie , Feigl Peter , Birkhofer Carina , Mohr Katharina , Roeder Maurice , Carle Stefan , Langer Simon , Tippel Franziska , Buchner Johannes , Fischer Gunter , Hausch Felix , Frick Manfred , Schwan Carsten , Aktories Klaus , Schiene-Fischer Cordelia , Barth Holger 
Published: March 2017

AbstractDiphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners. Moreover, pharmacological inhibition of the chaperone activity of Hsp90 and Hsp70 and of the peptidyl-prolyl cis/trans isomerase (PPIase) activity of Cyps and FKBPs protected cells from intoxication with diphtheria toxin and inhibited the pH-dependent trans-membrane transport of DTA into the cytosol. In conclusion, these host cell factors facilitate toxin uptake into human cells, which might lead to development of novel therapeutic strategies against diphtheria.
G-protein coupled receptor 15 mediates angiogenesis and cytoprotective function of thrombomodulin
Authors: Pan Bin , Wang Xiangmin , Nishioka Chie , Honda Goichi , Yokoyama Akihito , Zeng Lingyu , Xu Kailin , Ikezoe Takayuki 
Published: March 2017

AbstractThrombomodulin (TM) stimulates angiogenesis and protects vascular endothelial cells (ECs) via its fifth epidermal growth factor-like region (TME5); however, the cell surface receptor that mediates the pro-survival signaling activated by TM has remained unknown. We applied pull-down assay followed by MALDI-TOF MS and western blot analysis, and identified G-protein coupled receptor 15 (GPR15) as a binding partner of TME5. TME5 rescued growth inhibition and apoptosis caused by calcineurin inhibitor FK506 in vascular ECs isolated from wild type (WT) C57BL/6 mice. On the other hand, TME5 failed to protect ECs isolated from GPR15 knockout (GPR15 KO) mice from FK506-caused vascular injury. TME5 induced activation of extracellular signal-regulated kinase (ERK) and increased level of anti-apoptotic proteins in a GPR15 dependent manner. In addition, in vivo Matrigel plug angiogenesis assay found that TME5 stimulated angiogenesis in mice. TME5 promoted endothelial migration in vitro. Furthermore, TME5 increased production of NO in association with activated endothelial NO synthase (eNOS) in ECs. All these pro-angiogenesis functions of TME5 were abolished by knockout of GPR15. Our findings suggest that GPR15 plays an important role in mediating cytoprotective function as well as angiogenesis of TM.
Induction of pro-inflammatory genes by serum amyloid A1 in human amnion fibroblasts
Authors: Li Wenjiao , Wang Wangsheng , Zuo Rujuan , Liu Chao , Shu Qun , Ying Hao , Sun Kang 
Published: March 2017

AbstractSerum amyloid A1 (SAA1) is an acute response protein, which is mainly produced by the liver, during infection. However, it remains unknown whether SAA1 can be produced in human fetal membranes where it is able to elicit events pertinent to labor initiation. We demonstrated that SAA1 was expressed in the fibroblasts and epithelium of the amnion and the trophoblasts of the chorion. Further study in human amnion fibroblasts showed that SAA1 production was augmented by interleukin-1β (IL-1β) and cortisol alone and synergistically, and SAA1 in turn induced the expression of IL-1β, interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and PGE2 production. These effects of SAA1 were mediated through activation of the NF-κB, p38 and ERK1/2 pathways via the toll-like receptor 4 (TLR4). Inhibition of TLR4 attenuated not only SAA1-induced activation of NF-κB, p38 and ERK1/2 but also increases in IL-1β, IL-6 and COX-2 expression. Moreover, SAA1 expression was increased in human amnion tissue following spontaneous labor. In conclusion, this study has demonstrated for the first time that SAA1 can be produced in human fetal membranes, which can be greatly induced in the presence of proinflammatory cytokines and glucocorticoids thereby producing effects associated with parturition.
The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption
Authors: Pritchard Manon F. , Powell Lydia C. , Khan Saira , Griffiths Peter C. , Mansour Omar T. , Schweins Ralf , Beck Konrad , Buurma Niklaas J. , Dempsey Christopher E. , Wright Chris J. , Rye Philip D. , Hill Katja E. , Thomas David W. , Ferguson Elaine L. 
Published: March 2017

AbstractConcerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification.
The low affinity glucose transporter HxtB is also involved in glucose signalling and metabolism in Aspergillus nidulans
Authors: dos Reis Thaila Fernanda , Nitsche Benjamin M. , de Lima Pollyne Borborema Almeida , de Assis Leandro José , Mellado Laura , Harris Steven D. , Meyer Vera , dos Santos Renato A. Corrêa , Riaño-Pachón Diego M. , Ries Laure Nicolas Annick , Goldman Gustavo H. 
Published: March 2017

AbstractOne of the drawbacks during second-generation biofuel production from plant lignocellulosic biomass is the accumulation of glucose, the preferred carbon source of microorganisms, which causes the repression of hydrolytic enzyme secretion by industrially relevant filamentous fungi. Glucose sensing, subsequent transport and cellular signalling pathways have been barely elucidated in these organisms. This study therefore characterized the transcriptional response of the filamentous fungus Aspergillus nidulans to the presence of high and low glucose concentrations under continuous chemostat cultivation with the aim to identify novel factors involved in glucose sensing and signalling. Several transcription factor- and transporter-encoding genes were identified as being differentially regulated, including the previously characterized glucose and xylose transporter HxtB. HxtB was confirmed to be a low affinity glucose transporter, localizing to the plasma membrane under low- and high-glucose conditions. Furthermore, HxtB was shown to be involved in conidiation-related processes and may play a role in downstream glucose signalling. A gene predicted to encode the protein kinase PskA was also identified as being important for glucose metabolism. This study identified several proteins with predicted roles in glucose metabolic processes and provides a foundation for further investigation into the response of biotechnologically important filamentous fungi to glucose.
Migration phenology and breeding success are predicted by methylation of a photoperiodic gene in the barn swallow
Authors: Saino Nicola , Ambrosini Roberto , Albetti Benedetta , Caprioli Manuela , De Giorgio Barbara , Gatti Emanuele , Liechti Felix , Parolini Marco , Romano Andrea , Romano Maria , Scandolara Chiara , Gianfranceschi Luca , Bollati Valentina , Rubolini Diego 
Published: March 2017

AbstractIndividuals often considerably differ in the timing of their life-cycle events, with major consequences for individual fitness, and, ultimately, for population dynamics. Phenological variation can arise from genetic effects but also from epigenetic modifications in DNA expression and translation. Here, we tested if CpG methylation at the poly-Q and 5′-UTR loci of the photoperiodicClockgene predicted migration and breeding phenology of long-distance migratory barn swallows (Hirundo rustica) that were tracked year-round using light-level geolocators. Increasing methylation atClockpoly-Q was associated with earlier spring departure from the African wintering area, arrival date at the European breeding site, and breeding date. Higher methylation levels also predicted increased breeding success. Thus, we showed for the first time in any species that CpG methylation at a candidate gene may affect phenology and breeding performance. Methylation atClockmay be a candidate mechanism mediating phenological responses of migratory birds to ongoing climate change.