bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ergothioneine Biosynthesis and Functionality in the Opportunistic Fungal Pathogen, Aspergillus fumigatus
Authors: Sheridan Kevin J. , Lechner Beatrix Elisabeth , Keeffe Grainne O’ , Keller Markus A. , Werner Ernst R. , Lindner Herbert , Jones Gary W. , Haas Hubertus , Doyle Sean 
Published: October 2016

AbstractErgothioneine (EGT; 2-mercaptohistidine trimethylbetaine) is a trimethylated and sulphurised histidine derivative which exhibits antioxidant properties. Here we report that deletion of Aspergillus fumigatus egtA (AFUA_2G15650), which encodes a trimodular enzyme, abrogated EGT biosynthesis in this opportunistic pathogen. EGT biosynthetic deficiency in A. fumigatus significantly reduced resistance to elevated H2O2 and menadione, respectively, impaired gliotoxin production and resulted in attenuated conidiation. Quantitative proteomic analysis revealed substantial proteomic remodelling in ΔegtA compared to wild-type under both basal and ROS conditions, whereby the abundance of 290 proteins was altered. Specifically, the reciprocal differential abundance of cystathionine γ-synthase and β-lyase, respectively, influenced cystathionine availability to effect EGT biosynthesis. A combined deficiency in EGT biosynthesis and the oxidative stress response regulator Yap1, which led to extreme oxidative stress susceptibility, decreased resistance to heavy metals and production of the extracellular siderophore triacetylfusarinine C and increased accumulation of the intracellular siderophore ferricrocin. EGT dissipated H2O2in vitro, and elevated intracellular GSH levels accompanied abrogation of EGT biosynthesis. EGT deficiency only decreased resistance to high H2O2 levels which suggests functionality as an auxiliary antioxidant, required for growth at elevated oxidative stress conditions. Combined, these data reveal new interactions between cellular redox homeostasis, secondary metabolism and metal ion homeostasis.
The primary transcriptome of the Escherichia coli O104:H4 pAA plasmid and novel insights into its virulence gene expression and regulation
Authors: Berger Petya , Knödler Michael , Förstner Konrad U. , Berger Michael , Bertling Christian , Sharma Cynthia M. , Vogel Jörg , Karch Helge , Dobrindt Ulrich , Mellmann Alexander 
Published: October 2016

AbstractEscherichia coli O104:H4 (E. coli O104:H4), which caused a massive outbreak of acute gastroenteritis and hemolytic uremic syndrome in 2011, carries an aggregative adherence fimbriae I (AAF/I) encoding virulence plasmid, pAA. The importance of pAA in host-pathogen interaction and disease severity has been demonstrated, however, not much is known about its transcriptional organization and gene regulation. Here, we analyzed the pAA primary transcriptome using differential RNA sequencing, which allows for the high-throughput mapping of transcription start site (TSS) and non-coding RNA candidates. We identified 248 TSS candidates in the 74-kb pAA and only 21% of them could be assigned as TSS of annotated genes. We detected TSS for the majority of pAA-encoded virulence factors. Interestingly, we mapped TSS, which could allow for the transcriptional uncoupling of the AAF/I operon, and potentially regulatory antisense RNA candidates against the genes encoding dispersin and the serine protease SepA. Moreover, a computational search for transcription factor binding sites suggested for AggR-mediated activation of SepA expression, which was additionally experimentally validated. This work advances our understanding of the molecular basis of E. coli O104:H4 pathogenicity and provides a valuable resource for further characterization of pAA virulence gene regulation.
Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies
Authors: Clement Mathew , Pearson James A. , Gras Stephanie , van den Berg Hugo A. , Lissina Anya , Llewellyn-Lacey Sian , Willis Mark D. , Dockree Tamsin , McLaren James E. , Ekeruche-Makinde Julia , Gostick Emma , Robertson Neil P. , Rossjohn Jamie , Burrows Scott R. , Price David A. , Wong F. Susan , Peakman Mark , Skowera Ania , Wooldridge Linda 
Published: October 2016

AbstractCD8+ T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8+ T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8+ T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8+ T-cells are relatively CD8-independent. These generic differences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-specific TCRs according to the monomeric interaction affinity with cognate peptide-major histocompatibility complex class I (pMHCI). As a consequence, “blocking” anti-CD8 antibodies can suppress autoreactive CD8+ T-cell activation in a relatively selective manner. These findings provide a rational basis for the development and in vivo assessment of novel therapeutic strategies that preferentially target disease-relevant autoimmune responses within the CD8+ T-cell compartment.
Binding of cellulose binding modules reveal differences between cellulose substrates
Authors: Arola Suvi , Linder Markus B. 
Published: October 2016

AbstractThe interaction between cellulase enzymes and their substrates is of central importance to several technological and scientific challenges. Here we report that the binding of cellulose binding modules (CBM) from Trichoderma reesei cellulases Cel6A and Cel7A show a major difference in how they interact with substrates originating from wood compared to bacterial cellulose. We found that the CBM from TrCel7A recognizes the two substrates differently and as a consequence shows an unexpected way of binding. We show that the substrate has a large impact on the exchange rate of the studied CBM, and moreover, CBM-TrCel7A seems to have an additional mode of binding on wood derived cellulose but not on cellulose originating from bacterial source. This mode is not seen in double CBM (DCBM) constructs comprising both CBM-TrCel7A and CBM-TrCel6A. The linker length of DCBMs affects the binding properties, and slows down the exchange rates of the proteins and thus, can be used to analyze the differences between the single CBM. These results have impact on the cellulase research and offer new understanding on how these industrially relevant enzymes act.
Prognosis of alcohol-associated lactic acidosis in critically ill patients: an 8-year study
Authors: Yang Chun-Chieh , Chan Khee-Siang , Tseng Kuei-Ling , Weng Shih-Feng 
Published: October 2016

AbstractLactic acidosis is common in critical care; by contrast, a subtype called alcohol-associated lactic acidosis (AALA) is rarely encountered. The primary purpose of this study was to determine the prognosis of AALA in critically ill patients and the second aim was to determine whether the survival was associated to the peak blood lactate concentration. An 8-year retrospective analysis of adult patients admitted to the intensive care unit (ICU) with AALA between January 2007 and December 2014 was considered in a tertiary care hospital. In total, 23 patients were analyzed and the median peak blood lactate level was 15.9 mmol/L. Only 2 patients (8.7%) presented peak blood lactate levels <10 mmol/L. In this study, 21 patients survived from ICU and hospital, the mortality rate was 8.7%. The result indicted the survival of AALA was not associated with peak blood lactate concentration although survivors still had a better lactate clearance rate per hour than non-survivors. Moreover, AALA patients with coexisting sepsis presenting higher lactate clearance rate and shorter lactate clearance time than those of AALA patients with solely sepsis-related lactic acidosis.
Cation/Anion Substitution in Cu2ZnSnS4 for Improved Photovoltaic Performance
Authors: Ananthoju Balakrishna , Mohapatra Jeotikanta , Jangid Manoj K. , Bahadur D. , Medhekar N. V. , Aslam M. 
Published: October 2016

AbstractCations and anions are replaced with Fe, Mn, and Se in CZTS in order to control the formations of the secondary phase, the band gap, and the micro structure of Cu2ZnSnS4. We demonstrate a simplified synthesis strategy for a range of quaternary chalcogenide nanoparticles such as Cu2ZnSnS4 (CZTS), Cu2FeSnS4 (CFTS), Cu2MnSnS4 (CMTS), Cu2ZnSnSe4 (CZTSe), and Cu2ZnSn(S0.5Se0.5)4 (CZTSSe) by thermolysis of metal chloride precursors using long chain amine molecules. It is observed that the crystal structure, band gap and micro structure of the CZTS thin films are affected by the substitution of anion/cations. Moreover, secondary phases are not observed and grain sizes are enhanced significantly with selenium doping (grain size ~1 μm). The earth-abundant Cu2MSnS4/Se4 (M = Zn, Mn and Fe) nanoparticles have band gaps in the range of 1.04–1.51 eV with high optical-absorption coefficients (~104 cm−1) in the visible region. The power conversion efficiency of a CZTS solar cell is enhanced significantly, from 0.4% to 7.4% with selenium doping, within an active area of 1.1 ± 0.1 cm2. The observed changes in the device performance parameters might be ascribed to the variation of optical band gap and microstructure of the thin films. The performance of the device is at par with sputtered fabricated films, at similar scales.
Accurate and stable equal-pressure measurements of water vapor transmission rate reaching the 10−6 g m−2 day−1 range
Authors: Nakano Yoichiro , Yanase Takashi , Nagahama Taro , Yoshida Hajime , Shimada Toshihiro 
Published: October 2016

AbstractThe water vapor transmission rate (WVTR) of a gas barrier coating is a critically important parameter for flexible organic device packaging, but its accurate measurement without mechanical stress to ultrathin films has been a significant challenge in instrumental analysis. At the current stage, no reliable results have been reported in the range of 10−6 g m−2 day−1 that is required for organic light emitting diodes (OLEDs). In this article, we describe a solution for this difficult, but important measurement, involving enhanced sensitivity by a cold trap, stabilized temperature system, pumped sealing and calibration by a standard conductance element.
Enhanced cryopreservation of MSCs in microfluidic bioreactor by regulated shear flow
Authors: Bissoyi Akalabya , Bit Arindam , Singh Bikesh Kumar , Singh Abhishek Kumar , Patra Pradeep Kumar 
Published: October 2016

AbstractCell-matrix systems can be stored for longer period of time by means of cryopreservation. Cell-matrix and cell-cell interaction has been found to be critical in a number of basic biological processes. Tissue structure maintenance, cell secretary activity, cellular migration, and cell-cell communication all exist because of the presence of cell interactions. This complex and co-ordinated interaction between cellular constituents, extracellular matrix and adjacent cells has been identified as a significant contributor in the overall co-ordination of tissue. The prime objective of this investigation is to evaluate the effects of shear-stress and cell-substrate interaction in successful recovery of adherent human mesenchymal-stem-cells (hMSCs). A customized microfluidic bioreactor has been used for the purpose. We have measured the changes in focal-point-adhesion (FPAs) by changing induced shear stress inside the bioreactor. The findings indicate that with increase in shear stress, FPAs increases between substrate and MSCs. Further, experimental results show that increased FPAs (4e-3 μbar) enhances the cellular survivability of adherent MSCs. Probably, for the first time involvement of focal point interaction in the outcome of cryopreservation of MSCs has been clarified, and it proved a potentially new approach for modification of cryopreservation protocol by up-regulating focal point of cells to improve its clinical application.
Epidemiologic characteristics, knowledge and risk factors of unintentional burns in rural children in Zunyi, Southwest China
Authors: Shi Shangpeng , Yang Huajun , Hui Ya , Zhou Xiang , Wang Tao , Luo Ya , Xiang Huiyun , Shi Xiuquan 
Published: October 2016

AbstractWe investigated the knowledge level and risk factors for pediatric unintentional burns in rural Southwest China with an aim to provide basic evidence for the prevention strategies. A stratified sampling method was used to recruit 1842 rural children from 9 schools. Self-reported burns during the past 12 months and relevant risk factors were collected by questionnaires. The burn incidence of all surveyed children was 12.7% (95% confidence interval [95% CI] 11.2–14.2%). We found that burn incidence had a trend to increase with the increasing school grade level and a trend to decrease with increasing knowledge scores on burns. The top two causes of burns were hot liquids (36.3%) and hot object (29.5%). More than 30% of children had little knowledge about preventive measures and how to give first-aid after burns. The main risk factors for burns included female gender, left-behind children by parents who were working in cities, and poor mother school education level. As the incidence of pediatric unintentional burns was high in rural southwest China, schools, families, and local public health agencies should put efforts into health education targeting burn prevention and first-aid measures after burns, particularly in “left-behind” children and those with mothers with poor education.
Loss of Quiescence in von Hippel-Lindau Hemangioblastomas is Associated with Erythropoietin Signaling
Authors: Feldman Michael J. , Sizdahkhani Saman , Edwards Nancy A. , Merrill Marsha J. , Ray-Chaudhury Abhik , Zhuang Zhengping , Lonser Russell R. , Oldfield Edward H. , Chittiboina Prashant 
Published: October 2016

Abstractvon Hippel-Lindau (VHL) patients develop multiple central nervous system hemangioblastomas (HB). Some HBs become symptomatic with exponential growth or cyst formation following long periods of quiescence. Understanding the factors underlying growth in hemangioblastoma may lead to better strategies to arrest or prevent tumor growth. In 5 VHL patients, we resected quiescent hemangioblastomas (Q-HB) that were en-route during surgical access to symptomatic hemangioblastomas (S-HB), for matched tumor analysis. Quantitative reverse transcriptase analysis demonstrated a 2-fold increase in EPO expression in all S-HB, while 4/5 showed either Hypoxia Inducible Factor-1α or 2α upregulation. Additionally, all S-HB had increased phosphorylated erythropoietin (EPO) receptor and phosphorylated STAT-5 relative to matched Q-HB, with increased phosphorylated JAK-2 largely confined to the stromal cells in clusters within the tumors. These findings suggest that Q-HB to S-HB conversion may be associated with an erythropoietin-signaling loop. Furthermore, we found that EPO is detectable in cyst fluid from S-HB (n = 14), while absent in CSF (n = 1). Additionally, S-HB presentation or S-HB resection does not result in discernible change in serum EPO or hemoglobin (n = 60). These observations suggest that the altered erythropoietin signaling is focal and suggests that studying modulation of erythropoietin receptor pathway may lead to strategies in preventing HB growth.
Seipin deficiency alters brown adipose tissue thermogenesis and insulin sensitivity in a non-cell autonomous mode
Authors: Dollet L. , Magré J. , Joubert M. , Le May C. , Ayer A. , Arnaud L. , Pecqueur C. , Blouin V. , Cariou B. , Prieur X. 
Published: October 2016

AbstractLoss-of-function mutations in BSCL2 are responsible for Berardinelli-Seip congenital lipodystrophy, a rare disorder characterized by near absence of adipose tissue associated with insulin resistance. Seipin-deficient (Bscl2−/−) mice display an almost total loss of white adipose tissue (WAT) with residual brown adipose tissue (BAT). Previous cellular studies have shown that seipin deficiency alters white adipocyte differentiation. In this study, we aimed to decipher the consequences of seipin deficiency in BAT. Using a brown adipocyte cell-line, we show that seipin knockdown had very little effect on adipocyte differentiation without affecting insulin sensitivity and oxygen consumption. However, when submitted to cold acclimation or chronic β3 agonist treatment, Bscl2−/− mice displayed altered thermogenic capacity, despite several signs of BAT remodeling. Under cold activation, Bscl2−/− mice were able to maintain their body temperature when fed ad libitum, but not under short fasting. At control temperature (i.e. 21 °C), fasting worsened Bscl2−/− BAT properties. Finally, Bscl2−/− BAT displayed obvious signs of insulin resistance. Our results in these lipodystrophic mice strongly suggest that BAT activity relies on WAT as an energetic substrate provider and adipokine-producing organ. Therefore, the WAT/BAT dialogue is a key component of BAT integrity in guaranteeing its response to insulin and cold-activated adrenergic signals.
Use of reconstructed 3D VMEC equilibria to match effects of toroidally rotating discharges in DIII-D
Authors: Wingen A. , Wilcox R.S. , Cianciosa M.R. , Seal S.K. , Unterberg E.A. , Hanson J.M. , Hirshman S.P. , Lao L.L. , Logan N.C. , Paz-Soldan C. , Shafer M.W. 
Published: October 2016

Abstract
A technique for tokamak equilibrium reconstructions is used for multiple DIII-D discharges, including L-mode and H-mode cases when weakly 3D fields

(
δ
B

/

B
∼

10

−
3

)

are applied. The technique couples diagnostics to the non-linear, ideal MHD equilibrium solver VMEC, using the V3FIT code, to find the most likely 3D equilibrium based on a suite of measurements. It is demonstrated that V3FIT can be used to find non-linear 3D equilibria that are consistent with experimental measurements of the plasma response to very weak 3D perturbations, as well as with 2D profile measurements. Observations at DIII-D show that plasma rotation larger than 20 krad s−1 changes the relative phase between the applied 3D fields and the measured plasma response. Discharges with low averaged rotation (10 krad s−1) and peaked rotation profiles (40 krad s−1) are reconstructed. Similarities and differences to forward modeled VMEC equilibria, which do not include rotational effects, are shown. Toroidal phase shifts of up to

30

°

are found between the measured and forward modeled plasma responses at the highest values of rotation. The plasma response phases of reconstructed equilibra on the other hand match the measured ones. This is the first time V3FIT has been used to reconstruct weakly 3D tokamak equilibria.
yMap: an automated method to map yeast variants to protein modifications and functional regions
Authors: Arslan Ahmed , van Noort Vera 
Published: October 2016

Abstract

Summary
Recent advances in sequence technology result in large datasets of sequence variants. For the human genome, several tools are available to predict the impact of these variants on gene and protein functions. However, for model organisms such as yeast such tools are lacking, specifically to predict the effect of protein sequence altering variants on the protein level. We present a python framework that enables users to map in a fully automated fashion large set of variants to protein functional regions and post-translationally modified residues. Furthermore, we provide the user with the possibility to retrieve predicted functional information on modified residues from other resources for example that are predicted to play a role in protein-protein interactions. The results are complemented by statistical tests to highlight the significance of underlying functions and pathways affected by mutations. We show the application of this package on a yeast dataset derived from a recent evolutionary experiment on adaptation to ethanol.

Availability and Implementation
The package is available from https://github.com/CSB-KUL/yMap and is implemented in Python.

Supplementary information
Supplementary data are available at Bioinformatics online.
Chromosomal dynamics predicted by an elastic network model explains genome-wide accessibility and long-range couplings
Authors: Sauerwald Natalie , Zhang She , Kingsford Carl , Bahar Ivet 
Published: October 2016

AbstractUnderstanding the three-dimensional (3D) architecture of the chromatin and its relation to gene expression and regulation is fundamental to understanding how the genome functions. Advances in Hi-C technology now permit us to have a glimpse into the 3D genome organization and identify topologically associated domains (TADs), but we still lack an understanding of the structural dynamics of chromosomes. The dynamic couplings between regions separated by large genomic distances (> 50 megabases) have yet to be characterized. We adapted a well-established protein-modeling framework, the Gaussian Network Model (GNM), to the task of modeling chromatin dynamics using Hi-C contact data. We show that the GNM can identify structural dynamics at multiple scales: it can quantify the fluctuations in the positions of gene loci, find large genomic compartments and smaller TADs that undergo en-bloc movements, and identify dynamically coupled distal regions along the chromosomes. We show that the predictions of the GNM correlate well with DNase-seq and ATAC-seq measurements on accessibility, the previously identified A and B compartments of chromatin structure, and pairs of interacting loci identified by ChIA-PET. We describe a method to use the GNM to identify novel cross-correlated distal domains (CCDDs) representing regions of long-range dynamic coupling and show that CCDDs are often associated with increased gene coexpression using a large-scale analysis of 212 expression experiments. Together, these results show that GNM provides a mathematically well-founded unified framework for assessing chromatin dynamics and the structural basis of genome-wide observations.
Identification of new bacterial type III secreted effectors with a recursive Hidden Markov Model profile-alignment strategy
Authors: Cheng Xi , Hui Xinjie , White Aaron P. , Guo Zhirong , Hu Yueming , Wang Yejun 
Published: October 2016

AbstractTo identify new bacterial type III secreted effectors is computationally a big challenge. At least a dozen machine learning algorithms have been developed, but so far have only achieved limited success. Sequence similarity appears important for biologists but is frequently neglected by algorithm developers for effector prediction, although large success was achieved in the field with this strategy a decade ago. In this study, we propose a recursive sequence alignment strategy with Hidden Markov Models, to comprehensively find homologs of known YopJ/P full-length proteins, effector domains and N-terminal signal sequences. Using this method, we identified 155 different YopJ/P-family effectors and 59 proteins with YopJ/P N-terminal signal sequences from 27 genera and more than 70 species. Among these genera, we also identified one type III secretion system (T3SS) fromUliginosibacteriumand two T3SSs fromRhizobacterfor the first time. Higher conservation of effector domains, N-terminal fusion of signal sequences to other effectors, and the exchange of N-terminal signal sequences between different effector proteins were frequently observed for YopJ/P-family proteins. This made it feasible to identify new effectors based on separate similarity screening for the N-terminal signal peptides and the effector domains of known effectors. This method can also be applied to search for homologues of other known T3SS effectors.