bluuebunny/crossref_metadata_2025_split huggingface dataset:
Public Support for Increasing Women and Minority MPs
Authors: Bolzendahl Catherine , Coffé Hilde 
Published: June 2019

AbstractMost democracies fail to provide equal representation and tend to have an overrepresentation of men from the upper class and the majority racial or ethnic group. We investigate public support for increasing the number of women and indigenous Māori members of parliament (MPs) in the New Zealand Parliament, both in general and through specific mechanisms such as quotas and reserved seats. We offer three explanations: descriptive (group identity), substantive (issue alignment), and symbolic (socioeconomic and political equity concerns). Using data from the 2014 New Zealand Election Study, we found that shared identity (descriptive) matters for all measures of increased representation, but especially for Māori respondent support of increased Māori MPs. Support for increasing the proportion of Māori MPs is also strongly driven by substantive concerns, as measured by support for keeping the Treaty of Waitangi in law. Support for increasing the number of women MPs is driven most strongly by symbolic concerns (measured as increased government social spending and efforts to reduce income differences). Overall, respondents favor retaining the current number of reserved seats for Māori MP representation, whereas informal efforts (rather than quotas) are strongly preferred for increasing the number of women MPs.
Parkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth
Authors: Chen Rongmin , Park Han-A , Mnatsakanyan Nelli , Niu Yulong , Licznerski Pawel , Wu Jing , Miranda Paige , Graham Morven , Tang Jack , Boon Agnita J. W. , Cossu Giovanni , Mandemakers Wim , Bonifati Vincenzo , Smith Peter J. S. , Alavian Kambiz N. , Jonas Elizabeth A. 
Published: June 2019

AbstractFamilial Parkinson’s disease (PD) protein DJ-1 mutations are linked to early onset PD. We have found that DJ-1 binds directly to the F1FO ATP synthase β subunit. DJ-1’s interaction with the β subunit decreased mitochondrial uncoupling and enhanced ATP production efficiency while in contrast mutations in DJ-1 or DJ-1 knockout increased mitochondrial uncoupling, and depolarized neuronal mitochondria. In mesencephalic DJ-1 KO cultures, there was a progressive loss of neuronal process extension. This was ameliorated by a pharmacological reagent, dexpramipexole, that binds to ATP synthase, closing a mitochondrial inner membrane leak and enhancing ATP synthase efficiency. ATP synthase c-subunit can form an uncoupling channel; we measured, therefore, ATP synthase F1 (β subunit) and c-subunit protein levels. We found that ATP synthase β subunit protein level in the DJ-1 KO neurons was approximately half that found in their wild-type counterparts, comprising a severe defect in ATP synthase stoichiometry and unmasking c-subunit. We suggest that DJ-1 enhances dopaminergic cell metabolism and growth by its regulation of ATP synthase protein components.
KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe
Authors: Bery Nicolas , Legg Sandrine , Debreczeni Judit , Breed Jason , Embrey Kevin , Stubbs Christopher , Kolasinska-Zwierz Paulina , Barrett Nathalie , Marwood Rose , Watson Jo , Tart Jon , Overman Ross , Miller Ami , Phillips Christopher , Minter Ralph , Rabbitts Terence H. 
Published: June 2019

AbstractInhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that specifically inhibit the KRAS isoform by binding to an allosteric site encompassing the region around KRAS-specific residue histidine 95 at the helix α3/loop 7/helix α4 interface. We show that these DARPins specifically inhibit KRAS/effector interactions and the dependent downstream signalling pathways in cancer cells. Binding by the DARPins at that region influences KRAS/effector interactions in different ways, including KRAS nucleotide exchange and inhibiting KRAS dimerization at the plasma membrane. These results highlight the importance of targeting the α3/loop 7/α4 interface, a previously untargeted site in RAS, for specifically inhibiting KRAS function.
Abundance of bacterial Type VI secretion system components measured by targeted proteomics
Authors: Lin Lin , Lezan Emmanuelle , Schmidt Alexander , Basler Marek 
Published: June 2019

AbstractThe Type VI secretion system (T6SS) is important for bacterial competition as well as virulence in many Gram-negative bacteria and its dynamics and regulation varies significantly between species. To gain insights into the mechanisms regulating T6SS assembly, we apply targeted proteomics to determine the abundance of the key T6SS components in Vibrio cholerae, Pseudomonas aeruginosa and Acinetobacter baylyi. We show that while there are species specific exceptions, the abundance of most components is similar in all three bacteria and ranges from less than hundred to tens of thousands of copies per cell. The comparison of T6SS dynamics and protein abundance in V. cholerae grown under various conditions suggests that the critical component TssE and the secreted protein VasX are unstable and this diminishes T6SS assembly when protein synthesis is limited. Our quantitative analysis opens possibilities to build realistic models of T6SS assembly and to identify principles of T6SS regulation in various species.
Simulating multiple faceted variability in single cell RNA sequencing
Authors: Zhang Xiuwei , Xu Chenling , Yosef Nir 
Published: June 2019

AbstractThe abundance of new computational methods for processing and interpreting transcriptomes at a single cell level raises the need for in silico platforms for evaluation and validation. Here, we present SymSim, a simulator that explicitly models the processes that give rise to data observed in single cell RNA-Seq experiments. The components of the SymSim pipeline pertain to the three primary sources of variation in single cell RNA-Seq data: noise intrinsic to the process of transcription, extrinsic variation indicative of different cell states (both discrete and continuous), and technical variation due to low sensitivity and measurement noise and bias. We demonstrate how SymSim can be used for benchmarking methods for clustering, differential expression and trajectory inference, and for examining the effects of various parameters on their performance. We also show how SymSim can be used to evaluate the number of cells required to detect a rare population under various scenarios.
Identification of a genomic enhancer that enforces proper apoptosis induction in thymic negative selection
Authors: Hojo Miki Arai , Masuda Kyoko , Hojo Hiroaki , Nagahata Yosuke , Yasuda Keiko , Ohara Daiya , Takeuchi Yusuke , Hirota Keiji , Suzuki Yutaka , Kawamoto Hiroshi , Kawaoka Shinpei 
Published: June 2019

AbstractDuring thymic negative selection, autoreactive thymocytes carrying T cell receptor (TCR) with overtly strong affinity to self-MHC/self-peptide are removed by Bim-dependent apoptosis, but how Bim is specifically regulated to link TCR activation and apoptosis induction is unclear. Here we identify a murine T cell-specific genomic enhancer EBAB (Bub1-Acoxl-Bim), whose deletion leads to accumulation of thymocytes expressing high affinity TCRs. Consistently, EBAB knockout mice have defective negative selection and fail to delete autoreactive thymocytes in various settings, with this defect accompanied by reduced Bim expression and apoptosis induction. By contrast, EBAB is dispensable for maintaining peripheral T cell homeostasis via Bim-dependent pathways. Our data thus implicate EBAB as an important, developmental stage-specific regulator of Bim expression and apoptosis induction to enforce thymic negative selection and suppress autoimmunity. Our study unravels a part of genomic enhancer codes that underlie complex and context-dependent gene regulation in TCR signaling.
Identifying the structure of Zn-N2 active sites and structural activation
Authors: Li Feng , Bu Yunfei , Han Gao-Feng , Noh Hyuk-Jun , Kim Seok-Jin , Ahmad Ishfaq , Lu Yalin , Zhang Peng , Jeong Hu Young , Fu Zhengping , Zhong Qin , Baek Jong-Beom 
Published: June 2019

AbstractIdentification of active sites is one of the main obstacles to rational design of catalysts for diverse applications. Fundamental insight into the identification of the structure of active sites and structural contributions for catalytic performance are still lacking. Recently, X-ray absorption spectroscopy (XAS) and density functional theory (DFT) provide important tools to disclose the electronic, geometric and catalytic natures of active sites. Herein, we demonstrate the structural identification of Zn-N2 active sites with both experimental/theoretical X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) spectra. Further DFT calculations reveal that the oxygen species activation on Zn-N2 active sites is significantly enhanced, which can accelerate the reduction of oxygen with high selectivity, according well with the experimental results. This work highlights the identification and investigation of Zn-N2 active sites, providing a regular principle to obtain deep insight into the nature of catalysts for various catalytic applications.
Pairfield fluctuations of a 2D Hubbard model
Authors: Maier Thomas A. , Scalapino Douglas J. 
Published: June 2019

AbstractAt temperatures above the superconducting transition temperature, the pairfield susceptibility provides information on the nature of the pairfield fluctuations. Here, we study the d-wave pairfield susceptibility of a 2D Hubbard model for a doping which has a pseudogap (PG) and for a doping which does not. In both cases, there will be a region of Kosterlitz–Thouless fluctuations as the transition at TKT is approached. Above this region, we find evidence for pairfield-order parameter-phase fluctuations for dopings with a PG and BCS Cooper pair fluctuations for dopings without a PG.
Activity/exercise-induced changes in the liver transcriptome after chronic spinal cord injury
Authors: Chariker Julia H. , Ohri Sujata Saraswat , Gomes Cynthia , Brabazon Fiona , Harman Kathryn A. , DeVeau Kathryn M. , Magnuson David S. K. , Hetman Michal , Petruska Jeffrey C. , Whittemore Scott R. , Rouchka Eric C. 
Published: June 2019

AbstractMulti-organ dysfunction is a major complication after spinal cord injury (SCI). In addition to local injury within the spinal cord, SCI causes major disruption to the peripheral organ innervation and regulation. The liver contains sympathetic, parasympathetic, and small sensory axons. The bi-directional signaling of sensory dorsal root ganglion (DRG) neurons that provide both efferent and afferent information is of key importance as it allows sensory neurons and peripheral organs to affect each other. SCI-induced liver inflammation precedes and may exacerbate intraspinal inflammation and pathology after SCI, which may be modulated by activity and exercise. In this study, we collected comprehensive gene expression data through RNA sequencing of liver tissue from rats with chronic SCI to determine the effects of activity and exercise on those expression patterns. The sequenced data are of high quality and show a high alignment rate to the Rn6 genome. Gene expression is demonstrated for genes associated with known liver pathologies. UCSC Genome Browser expression tracks are provided with the data to facilitate exploration of the samples.
Hypothalamus-pituitary-gonad axis transcriptome profiling for sex differentiation in Acipenser sinensis
Authors: Du Hejun , Jian Jianbo , Wang Binzhong , Liu Xueqing , Chen Jianwei , Xiao Kan , Xia Jinquan , Yang Jing , Gao Yong , Chen Lei 
Published: June 2019

AbstractChinese sturgeon (Acipenser sinensis), a critically endangered Acipenseridae family member, is one of the largest anadromous, native fish in China. Numerous research programmes and protection agencies have focused on breeding and preserving this endangered species. However, available information is limited on the different stages of sex development, especially on the reproductive regulation of the hypothalamus-pituitary-gonad (HPG) axis of A. sinensis. To unravel the mechanism of gene interactions during sex differentiation and gonad development of A. sinensis, we performed transcriptome sequencing using HPG samples from male and female A. sinensis in two developmental stages. In this study, 271.19 Gb high-quality transcriptome data were obtained from 45 samples belonging to 15 individuals (six in stage I, six males and three females in stage II). These transcriptomic data will help us understand the reproductive regulation of the HPG axis in the development stages of A. sinensis and provide important reference data for genomic and genetic studies in A. sinensis and related species.
Carbon metabolism modulates the efficacy of drugs targeting the cytochrome bc1:aa3 in Mycobacterium tuberculosis
Authors: Kalia Nitin P. , Shi Lee Bei , Ab Rahman Nurlilah B. , Moraski Garrett C. , Miller Marvin J. , Pethe Kevin 
Published: June 2019

AbstractThe influence of carbon metabolism on oxidative phosphorylation is poorly understood in mycobacteria.M.tuberculosisexpresses two respiratory terminal oxidases, the cytochromebc1:aa3and the cytochromebdoxidase, which are jointly required for oxidative phosphorylation and mycobacterial viability. The essentiality of the cytochromebc1:aa3for optimum growth is illustrated by its vulnerability to chemical inhibition by the clinical drug candidate Q203 and several other chemical series. The cytochromebdoxidase is not strictly essential for growth but is required to maintain bioenergetics when the function of the cytochromebc1:aa3is compromised. In this study, we observed that the potency of drugs targeting the cytochromebc1:aa3is influenced by carbon metabolism. The efficacy of Q203 and related derivatives was alleviated by glycerol supplementation. The negative effect of glycerol supplementation on Q203 potency correlated with an upregulation of the cytochromebdoxidase-encodingcydABDCoperon. Upon deletion ofcydAB, the detrimental effect of glycerol on the potency of Q203 was abrogated. The same phenomenon was also observed in recent clinical isolates, but to a lesser extent compared to the laboratory-adapted strain H37Rv. This study reinforces the importance of optimizingin vitroculture conditions for drug evaluation in mycobacteria, a factor which appeared to be particularly essential for drugs targeting the cytochromebc1:aa3terminal oxidase.
First evidence for an association between joint hypermobility and excitability in a non-human species, the domestic dog
Authors: Bowen Jonathan , Fatjó Jaume , Serpell James A. , Bulbena-Cabré Andrea , Leighton Eldin , Bulbena Antoni 
Published: June 2019

AbstractThere is a well-established relationship between joint hypermobility and anxiety in humans, that has not previously been investigated in other species. A population of 5575 assistance dogs were scored for both hip hypermobility and 13 behaviour characteristics using previously validated methods. Our results suggest a positive association between hip joint hypermobility and emotional arousal in domestic dogs, which parallel results found in people.
An Unobtrusive and Calibration-free Blood Pressure Estimation Method using Photoplethysmography and Biometrics
Authors: Xing Xiaoman , Ma Zhimin , Zhang Mingyou , Zhou Ying , Dong Wenfei , Song Mingxuan 
Published: June 2019

AbstractWe introduce a novel paradigm to unobtrusively and optically measure blood pressure (BP) without calibration. The algorithm combines photoplethysmography (PPG) waveform analysis and biometrics to estimate BP, and was evaluated in subjects with various age, height, weight and BP levels (n = 1249). In the young population (<50 years old) with low, medium and high systolic blood pressures (SBP, <120 mmHg; 120–139 mmHg; ≥140 mmHg), the fitting errors are 6.3 ± 7.2, −3.9 ± 7.2 and −20.2 ± 14.2 mmHg for SBP respectively; In the older population (>50 years old) with the same categories, the fitting errors are 12.8 ± 9.0, 0.5 ± 8.2 and −14.6 ± 11.5 mmHg for SBP respectively. A simple personalized calibration reduces fitting errors significantly (n = 147), and good peripheral perfusion helps to improve the fitting accuracy. In conclusion, PPG may be used to calculate BP without calibration in certain populations. When calibrated, it shows great potential to serially monitor BP fluctuation, which can bring tremendous economic and health benefits.
Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals
Authors: Broughton Kathleen M. , Khieu Tiffany , Nguyen Nicky , Rosa Michael , Mohsin Sadia , Quijada Pearl , Wang Bingyan J. , Echeagaray Oscar H. , Kubli Dieter A. , Kim Taeyong , Firouzi Fareheh , Monsanto Megan M. , Gude Natalie A. , Adamson Robert M. , Dembitsky Walter P. , Davis Michael E. , Sussman Mark A. 
Published: June 2019

AbstractCardiomyocyte ploidy has been described but remains obscure in cardiac interstitial cells. Ploidy of c-kit+ cardiac interstitial cells was assessed using confocal, karyotypic, and flow cytometric technique. Notable differences were found between rodent (rat, mouse) c-kit+ cardiac interstitial cells possessing mononuclear tetraploid (4n) content, compared to large mammals (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in human c-kit+ cardiac interstitial cells and a mixture of diploid and tetraploid content in mouse. Downregulation of the p53 signaling pathway provides evidence why rodent, but not human, c-kit+ cardiac interstitial cells escape replicative senescence. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse c-kit+ cardiac interstitial cells, alluding to functional divergences. Collectively, these data reveal notable species-specific biological differences in c-kit+ cardiac interstitial cells, which could account for challenges in extrapolation of myocardial from preclinical studies to clinical trials.
Proteomic response of marine-derived Staphylococcus cohnii #NIOSBK35 to varying Cr(vi) concentrations
Authors: Shah Shruti , Damare Samir 
Published: June 2019

Abstract
Chromium in its hexavalent state is a water-soluble and toxic element to living organisms present in the environment. However, some organisms are resistant and reduce the toxic forms of Cr(vi) to less toxic or non-toxic forms. A global proteomic analysis of Staphylococcus sp. #NIOSBK35 under different chromate concentrations (0, 100, 200 and 300 mg L−1) at different time points in its growth stages (6, 9, 12, 18, 24 and 36 h) resulted in the identification of 878 proteins. Of all the proteins expressed, 13 proteins [23 rDNA (uracil-5-) methyltransferase RumA, multidrug ABC transporter ATP binding protein, dihydroxy acid dehydratase, polysaccharide biosynthesis protein, etc.] were expressed only in the presence of chromium. 14 proteins were up-regulated in response to chromium(vi), namely, alkyl hydroperoxide reductase, ATP-dependent Zn metallopeptidase, hsp90- like protein, NAD (P)-dependent oxidoreductase, etc. Most of the proteins involved in normal cell functioning like 1-pyrroline-5-carboxylate dehydrogenase, ribosomal proteins (30S ribosomal protein S11, 30S ribosomal protein S2, and 50S ribosomal protein L32), aconitate hydratase, DNA primase, serine-tRNA ligase, phosphoenolpyruvate-protein phosphotransferase, enolase, sulfur transferase FdhD, etc. were found to be down-regulated. On grouping these proteins into their COG (cluster of orthologous groups) functional categories, they were found to be involved in translation, carbohydrate metabolism, stress proteins, amino acid transport and membrane transport mechanisms. The proteomic response given by Staphylococcus sp. #NIOSBK35 did not show expression of Cr-specific proteins, indicating a different mechanism of Cr-tolerance as the organism was able to survive and grow at high concentrations of Cr(vi).
Nitration-induced ubiquitination and degradation control quality of ERK1
Authors: Zhang Yuanya , Huang Xiahe , Wang Jinlong , Wang Xiaorong , Liu Xiaofei , Chen Yuhang , Xu Wu , Wang Yingchun 
Published: June 2019

Abstract
The mitogen-activated protein kinase ERK1/2 (ERKs, extracellular-regulated protein kinases) plays important roles in a wide spectrum of cellular processes and have been implicated in many disease states. The spatiotemporal regulation of ERK activity has been extensively studied. However, scarce information has been available regarding the quality control of the kinases to scavenge malfunctioning ERKs. Using site-specific mutagenesis and mass spectrometry, we found that the disruption of the conserved H-bond between Y210 and E237 of ERK1 through point mutation at or naturally occurring nitration on Y210 initiates a quality control program dependent on chaperon systems and CHIP (C-terminal of Hsp70-interacting protein)-mediated ubiquitination and degradation. The H-bond is also important for the quality control of ERK2, but through a distinct mechanism. These findings clearly demonstrate how malfunctioning ERKs are eliminated when cells are in certain stress conditions or unhealthy states, and could represent a general mechanism for scavenging malfunctioning kinases in stress conditions.
Differential gene expression in articular cartilage between rheumatoid arthritis and endemic Kashin–Beck disease
Authors: Gao Zongqiang , Duan Chen , Yu Fang-fang , Guo Xiong 
Published: June 2019

Abstract
Kashin–beck disease (KBD) is endemic chronic osteoarthrosis and its pathogenesis is still unclear. The present study aimed to explore differential gene expression in articular cartilage between patients with rheumatoid arthritis (RA) and KBD. Articular cartilages were collected from KBD and RA patients, and differentially expressed genes (DEGs) were analyzed by RNA-seq. The signaling pathway and biological process (BP) of the DEGs were identified by enrichment analysis. The protein–protein interaction (PPI) network of DEGs and the key genes of KBD were identified by network analysis with STRING and cytoscape software. We identified 167 immune-related DEGs in articular cartilage samples from KBD patients compared with RA. The up-regulation of MAPK signaling pathway and the down-regulation of signaling pathways such as toll-like receptor, janus kinase-signal transducers and activators of transcription, leukocyte migration, T-cell receptor and chemokine, and antigen processing and presentation were involved in KBD. We identified 137 genes nodes related with immune and mapped the PPI network diagram. BP analysis revealed that immune response, calcium ion homeostasis, blood vessel morphogenesis, inflammatory response, lymphocyte proliferation, and MAPK activation were involved in KBD. In conclusion, gene expression profiling can be used to identify the different mechanism of pathogenesis between KBD and RA.