bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supra-molecular assemblies of ORAI1 at rest precede local accumulation into punctae after activation
Authors: Peckys Diana B. , Gaa Daniel , Alansary Dalia , Niemeyer Barbara. A. , de Jonge Niels 
Published: January 2020

ABSTRACTThe Ca2+selective channel ORAI1 and endoplasmic reticulum (ER)-resident STIM proteins form the core of the channel complex mediating store operated Ca2+entry (SOCE). Using liquid phase electron microscopy (LPEM) the distribution of ORAI1 proteins was examined at rest and after SOCE-activation at nanoscale resolution. The analysis of over seven hundred thousand of ORAI1 positions showed that already at rest, a majority of the ORAI1 channels formed STIM-independent distinct supra-molecular clusters. Upon SOCE activation and in the presence of STIM proteins, ORAI1 assembled in micron-sized two-dimensional (2D) structures, such as the known punctae at the ER plasma membrane contact zones, but also in divergent structures such as strands, and ring-like shapes. Our results thus question the hypothesis that stochastically migrating single ORAI1 channels are trapped at regions containing activated STIM, and we propose instead that supra-molecular ORAI1 clusters fulfill an amplifying function for creating dense ORAI1 accumulations upon SOCE-activation.STATEMENT OF SIGNIFICANCEORAI1 proteins form channels mediating store operated Ca2+entry, an important trigger for many cellular functions, especially in the immune system. ORAI1 channels at rest are assumed to be randomly distributed in the plasma membrane, while they accumulate into so-called “punctae” upon activation, where binding by STIM proteins activate the Ca2+channels. Using liquid phase electron microscopy, we discovered that ORAI1 forms small, elongated clusters indicating the existence of supramolecular assemblies. The role of such supramolecular organization of ORAI1 is possibly an amplifying function for the effective creation of ORAI1 accumulations in punctae, since the binding of only one ORAI1 protein would trap a multiple of channels.
Comparison of de-duplication methods used by WHO Global Antimicrobial Resistance Surveillance System (GLASS) and Japan Nosocomial Infections Surveillance (JANIS) in the surveillance of antimicrobial resistance
Authors: Kajihara Toshiki , Yahara Koji , Stelling John , Eremin Sergey Romualdovich , Tornimbene Barbara , Thamlikitkul Visanu , Hirabayashi Aki , Anzai Eiko , Wakai Satoyo , Matsunaga Nobuaki , Hayakawa Kayoko , Ohmagari Norio , Sugai Motoyuki , Shibayama Keigo 
Published: January 2020

AbstractA major issue in the surveillance of antimicrobial resistance (AMR) is “de-duplication” or removal of repeated isolates, for which there exist multiple methods. The World Health Organization (WHO) Global Antimicrobial Resistance Surveillance System (GLASS) requires de-duplication by selecting only the first isolate of a given bacterial species per patient per surveillance period per specimen type per age group, gender, and infection origin stratification. However, no study on the comparative application of this method has been reported. The objective of this study was to evaluate differences in data tabulation between the WHO GLASS and the Japan Nosocomial Infections Surveillance (JANIS) system, which counts both patients and isolates after removing repeated isolates of the same bacterial species per multiresistance phenotype isolated from a patient within 30 days, regardless of specimen type. All bacterial data, consisting of approximately 8 million samples from 1795 Japanese hospitals in 2017 were exported from the JANIS database, and were tabulated using either the de-duplication algorithm of GLASS, or JANIS. We compared the tabulated results of the total number of patients whose blood and urine cultures were taken and of the percentage of resistant isolates ofEscherichia colifor each priority antibiotic. The number of patients per specimen type tabulated by the JANIS method was always smaller than that of GLASS. There was a small (< 3%) difference in the percentage of resistance ofE. colifor any antibiotic between the two methods in both out- and inpatient settings and blood and urine isolates. The two tabulation methods did not show considerable differences in terms of the tabulated percentages of resistance forE. coli. We further discuss how the use of GLASS tabulations to create a public software and website that could help to facilitate the understanding of and treatment against AMR.
Complete genome and phylogenetic analysis of bovine papillomavirus type 15 in Southern Xinjiang dairy cow
Authors: Hu Jianjun , Zhang Wanqi , Chauhan Surinder Singh , Shi Changqing , Song Yumeng , Qiu Zhitao , Zhao Yubing , Wang Zhehong , Cheng Long , Zhang Yingyu 
Published: January 2020

AbstractIn this study, the complete genome sequence of bovine papillomavirus (BPV) type 15 (BPV Aks-02), a novel putative BPV type from a skin sample of a cow in southern Xinjiang, China was determined by collecting cutaneous neoplastic lesion, followed by DNA extraction and amplicon sequencing. The complete genome consisted of 7189 base pairs (G+C content of 42.50%) that encoded five early (E8, E7, E1, E2, E4) and two late (L1 and L2) genes. The E7 protein contained a consensus CX2CX29CX2C zinc-binding domain and an LxCxE motif. The nucleotide sequence of the L1 open reading frame (ORF) was related mostly (99%) to the L1 ORF of putative type BAPV-3 reference strain from GenBank. Phylogenetic analysis and sequence similarities based on the L1 ORF suggest that BPV type (BPV Aks-02) clustered with members of genusXipapillomavirusas BPV15, and closely related toXipapillomavirus1.
Correlative cryo-structured illumination fluorescence microscopy and soft X-ray tomography elucidates reovirus intracellular release pathway
Authors: Kounatidis Ilias , Stanifer Megan L , Phillips Michael A. , Paul-Gilloteaux Perrine , Helligenstein Xavier , Wang Hongchang , Okolo Chidinma A. , Fish Thomas M. , Spink Matthew C. , Stuart David I. , Davis Ilan , Boulant Steeve , Grimes Jonathan M. , Dobbie Ian M. , Harkiolaki Maria 
Published: January 2020

AbstractImaging of biological matter across resolution scales presents the challenge of preserving the direct and unambiguous correlation of subject features from the macroscopic to the microscopic level. We present here a correlative imaging platform developed specifically for imaging cells in 3D, under cryogenic conditions. Rapid cryo-preservation of biological specimens is the current gold standard in sample preparation for ultrastructural analysis in X-ray imaging. However, cryogenic fluorescence localisation methods are by and large diffraction-limited and fail to deliver matching resolution. We addressed this technological gap by developing an integrated, user-friendly, platform for 3D correlative imaging of cells in cryo-preserved states using super-resolution structured illumination microscopy (SIM) in conjunction with soft X-ray tomography (SXT). The power of this new approach is demonstrated by studying the process of reovirus release from intracellular vesicles during the early stages of infection and identifying novel virus-induced structures.
Chemical, physical and biological triggers of evolutionary conserved Bcl-xL-mediated apoptosis
Authors: Ianevski Aleksandr , Kulesskiy Evgeny , Krpina Klara , Lou Guofeng , Aman Yahyah , Bugai Andrii , Aasumets Koit , Akimov Yevhen , Bulanova Daria , Gildemann Kiira , Arutyunyan Albert F. , Susova Olga Yu. , Zhuze Alexei L. , Ji Ping , Wang Wei , Holien Toril , Bugge Marit , Zusinaite Eva , Oksenych Valentyn , Lysvand Hilde , Gerhold Joachim M. , Bjørås Magnar , Johansen Pål , Waage Anders , Heckman Caroline , Fang Evandro F. , Kainov Denis E. 
Published: January 2020

ABSTRACTThe evidence that pan-Bcl-2 or Bcl-xL-specific inhibitors prematurely kill virus-infected or RNA/DNA-transfected cells provides rationale for investigating these apoptotic inducers further. Here, we show that Bcl-xL-specific agent A-1155463 prematurely kills cells of different origins and the small roundworms (C. elegans), when combined with DNA-damaging agent 4-nitroquinoline-1-oxide (4NQO). The synergistic effect of 4NQO-A-1155463 combination was p53-dependent, was associated with the release of Bad and Bax from Bcl-xL, which triggered mitochondrial outer membrane permeabilization (MOMP). Combinations of Bcl-xL-specific inhibitors with certain anticancer compounds or physical insults also killed cells. Collectively, our results suggest that biological, chemical and physical factors trigger evolutionary conserved Bcl-xL-mediated apoptotic pathway.
ComBat-Seq: batch effect adjustment for RNA-Seq count data
Authors: Zhang Yuqing , Parmigiani Giovanni , Johnson W. Evan 
Published: January 2020

AbstractThe benefit of integrating batches of genomic data to increase statistical power in differential expression is often hindered by batch effects, or unwanted variation in data caused by differences in technical factors across batches. It is therefore critical to effectively address batch effects in genomic data. Many existing methods for batch effect adjustment assume continuous, bell-shaped Gaussian distributions for data. However in RNA-Seq studies where data are skewed, over-dispersed counts, this assumption is not appropriate and may lead to erroneous results. Negative binomial regression models have been used to better capture the properties of counts. We developed a batch correction method, ComBat-Seq, using negative binomial regression. ComBat-Seq retains the integer nature of count data in RNA-Seq studies, making the batch adjusted data compatible with common differential expression software packages that require integer counts. We show in realistic simulations that the ComBat-Seq adjusted data result in better statistical power and control of false positives in differential expression, compared to data adjusted by the other available methods. We further demonstrated in a real data example where ComBat-Seq successfully removes batch effects and recovers the biological signal in the data.
Obesity-linked PPARγ S273 phosphorylation promotes insulin resistance through Growth Differentiation Factor 3
Authors: Hall Jessica A. , Ramachandran Deepti , Roh Hyun C. , DiSpirito Joanna R. , Belchior Thiago , Zushin Peter-James H. , Palmer Colin J. , Hong Shangyu , Mina Amir I. , Liu Bingyang , Deng Zhaoming , Aryal Pratik , Jacobs Christopher , Tenen Danielle , Brown Chester W. , Charles Julia F. , Shulman Gerald I. , Kahn Barbara B. , Tsai Linus T.Y. , Rosen Evan D. , Spiegelman Bruce M. , Banks Alexander S. 
Published: January 2020

AbstractOvernutrition and obesity promote adipose tissue dysfunction, often leading to systemic insulin resistance. The thiazolidinediones (TZDs) are a potent class of insulin-sensitizing drugs and ligands of PPARγ that improve insulin sensitivity, but their use is limited due to significant side effects. Recently, we demonstrated a mechanism by which TZDs improve insulin sensitivity distinct from receptor agonism and adipogenesis: reversal of obesity-linked phosphorylation of PPARγ at Serine 273. However, the role of this modification has not been tested genetically. Here we demonstrate that mice encoding an allele of PPARγ which cannot be phosphorylated at S273 are protected from insulin resistance, without exhibiting differences in body weight or TZD-associated side effects. Indeed, hyperinsulinemic-euglycemic clamp experiments confirm improved insulin sensitivity, as evidenced by increased whole-body glucose uptake. RNA-seq experiments reveal PPARγ S273 phosphorylation specifically enhances transcription of Gdf3, a BMP family member. Ectopic expression of Gdf3 is sufficient to induce insulin resistance in lean, healthy mice. We find that Gdf3 can impact metabolism by inhibition of BMP signaling. Together, these results highlight the diabetogenic role of PPARγ S273 phosphorylation and focuses attention on a putative target, Gdf3.
Pan-cancer landscape of homologous recombination deficiency
Authors: Nguyen Luan , Martens John , Van Hoeck Arne , Cuppen Edwin 
Published: January 2020

AbstractHomologous recombination deficiency (HRD) results in impaired double strand break repair and is a frequent driver of tumorigenesis. Here, we developed a genome-wide mutational scar-based pan-cancerClassifier ofHOmologousRecombinationDeficiency (CHORD) that can discriminate BRCA1- and BRCA2-subtypes. Analysis of a metastatic (n=3,504) and primary (n=1,854) pan-cancer cohort revealed HRD was most frequent in ovarian and breast cancer, followed by pancreatic and prostate cancer. Biallelic inactivation of BRCA1, BRCA2, RAD51C or PALB2 was the most common genetic cause of HRD, with RAD51C and PALB2 inactivation resulting in BRCA2-type HRD. While the specific genetic cause of HRD was cancer type specific, biallelic inactivation was predominantly associated with loss-of-heterozygosity (LOH), with increased contribution of deep deletions in prostate cancer. Our results demonstrate the value of pan-cancer genomics-based HRD testing and its potential diagnostic value for patient stratification towards treatment with e.g. poly ADP-ribose polymerase inhibitors (PARPi).
Structural analysis ofSulfolobus solfataricusTF55β chaperonin in open and filamentous states
Authors: Zeng Yi Cheng , Sobti Meghna , Stewart Alastair G 
Published: January 2020

AbstractChaperonins are biomolecular complexes that assist protein folding. Thermophilic Factor 55 (TF55) is a group II chaperonin found in the archaeal genusSulfolobusthat has α, β and γ subunits. Using cryo-electron microscopy, we have determined the structure of the β-only complex ofS. solfataricusTF55 complexes to 3.6–4.2 Å resolution and a filamentous form to 5.2 Å resolution. The structures of the TF55β complexes formed in the presence of ADP or ATP highlighted an open state in which nucleotide exchange can occur before progressing in the refolding cycle. The structure of the filamentous state indicates how helical protrusions facilitate end-on-end interactions.SynopsisThe isolated complex and filamentous forms of TF55β chaperonin from the thermophilic archaeaSulfolobus solfataricusare reported. Using cryo-EM, nucleotide-bound complexes of TF55β at 3.6–4.2 Å resolution reveal an open conformation, while a 5.2 Å reconstruction of the filamentous chaperonin reveals contacts at the apical domain similar to crystal-packed structures.
Chemotaxis overrides Barotaxis during Directional Decision-Making inDictyostelium discoideum
Authors: Belotti Yuri , McGloin David , Weijer Cornelis J. 
Published: January 2020

AbstractNeutrophils and dendritic cells have, besides their well characterised chemotactic movement responses, been shown to be able to detect and respond to local differences in hydraulic resistance (barotaxis). Furthermore, for neutrophils, it has been suggested that barotaxis overrides chemotaxis. Here, we investigate whether Dictyostelium cells also respond to hydraulic resistance or primarily to chemical gradients using an asymmetric bifurcating micro-channel. This channel design allows us to decouple hydraulic and chemical stimuli, by providing a choice between moving up a chemical gradient or down a chemical gradient into a channel with 100 times lower hydraulic resistance. Under these conditions chemotaxis always overrides barotaxis. Cells confronted by a microchannel bifurcation are observed to often partially split their leading edge and to start moving into both channels. Cells in steeper cAMP gradients, that move faster, split more readily. The decision to retract the pseudopod moving away from the cAMP source is made when the average velocity of the pseudopod moving up the cAMP gradient is 20% higher than the average velocity of the pseudopod moving down the gradient. Surprisingly, this decision threshold is independent of the steepness of the cAMP gradient and speed of movement. It indicates that a critical force imbalance threshold underlies the repolarisation decision.Significance StatementWe investigate the directional ‘decision-making’ of Dictyostelium discoideum cells migrating within engineered micro-channels harbouring asymmetric bifurcations. Unlike neutrophils and immature dendritic cells, Dictyostelium cells strongly prioritise chemical over barotactic guidance cues. Cells in steeper cAMP gradients migrate at higher speeds, split their leading edges more readily when confronted with a bifurcation in the channel. The decision to retract a pseudopod pointing in an unfavourable direction occurs when a critical tension gradient between two competing pseudopods is surpassed. These experiments show that although barotaxis is not a major guidance cue, cellular mechanics plays a major role in leading edge dynamics, including front splitting and polarisation and retraction.
Single molecule mass photometry of nucleic acids
Authors: Li Yiwen , Struwe Weston B. , Kukura Philipp 
Published: January 2020

ABSTRACTMass photometry is a recently developed methodology capable of detection, imaging and mass measurement of individual proteins under solution conditions. Here, we show that this approach is equally applicable to nucleic acids, enabling their facile, rapid and accurate detection and quantification using sub-picomoles of sample. The ability to count individual molecules directly measures relative concentrations in complex mixtures without need for separation. Using a dsDNA ladder, we find a linear relationship between the number of bases per molecule and the associated imaging contrast for up to 1200 bp, enabling us to quantify dsDNA length with 4 bp accuracy. These results introduce mass photometry as an accurate and rapid single molecule method complementary to existing DNA characterisation techniques.
When do customer orientation and innovation capabilities matter? An investigation of contextual impacts
Authors: Racela Olimpia C. , Thoumrungroje Amonrat 
Published: January 2020

PurposeGrounded on resource-advantage (R-A) theory, the purpose of this paper is to investigate how customer orientation, as a higher-order or interconnected operant resource, enhances firm performance through creativity capability (i.e. idea generation and problem solving) and innovation capability (i.e. the implementation of creative ideas) – among firms of different sizes and within different market contexts. The authors conceptualize customer orientation as a firm’s capacity to create and deliver superior customer value through the processing of market intelligence, as demonstrated by the firm’s composite operant resources of market-sensing, customer-relating and customer-response capabilities.Design/methodology/approachData were collected via qualitative in-depth interviews for scale development followed by a mail questionnaire survey for quantitative responses. A final sample size of 190 firms based in Thailand participated and the data were analyzed using structural equation modeling and bootstrapping multi-group comparisons to investigate the hypothesized mediation and moderation effects.FindingsCustomer orientation enhances organizational creativity and innovation capabilities, which improve firm revenue and financial performance. The relationships among customer orientation, creativity capability, innovation capability and firm performance vary depending on firm size, market dynamism and customer type.Practical implicationsManagers need to consider contextual factors, particularly firm size, market dynamism and the nature of their buyer markets as key contingencies in their resource deployment decisions intended to develop customer orientation and innovation capabilities.Originality/valueThis study advocates R-A theory by empirically revealing how different hierarchical resources within a firm are intertwined to provide firms with competitive R-A. The findings further highlight a contingent nature of customer orientation–innovation–performance relationships among firms in an emerging economy.
Rethinking the effect of floods and financial development on economic growth
Authors: Parida Yashobanta , Prasad Dash Devi 
Published: January 2020

Purpose
The purpose of this paper is to evaluate the effect of floods and the role of financial development on per capita gross state domestic product (GSDP) growth, controlling for growth-enhancing factors across Indian states.

Design/methodology/approach
The paper uses the pooled mean group (PMG) method using state-level panel data for 19 Indian states over the period 1981-2011.

Findings
The PMG estimate shows that floods negatively affect the per capita GSDP growth in the long run. The results show that the mean of economic losses, the population affected and the area affected by floods increase by 10 per cent, leading to a decline in per capita GSDP growth by 0.0303, 0.0633 and 0.0232 per cent, respectively, in the long run. Furthermore, the population affected by floods exerts a higher adverse impact on the per capita GSDP growth compared to other flood measures. The results further show that states with better financial development experience a higher per capita GSDP growth, supported by additional capital expenditure, enrolment in higher education, better road infrastructure and higher urbanization. The crime rate is negatively correlated with per capita GSDP growth.

Originality/value
The results based on PMG estimates suggest that not only floods but also crime activities adversely affect the per capita GSDP growth across Indian states. Better financial market increases the per capita GSDP growth in the long run. This study not only contributes to empirical growth literature but also provides some useful policy suggestions. Moreover, the results lead to the conclusion that long-term flood management policies are essential to mitigate the adverse impact of floods on per capita GSDP growth across Indian states.
Risk of natural hazards and the coping capacity of the South African community in Auckland
Authors: Odiase Osamuede , Wilkinson Suzanne , Neef Andreas 
Published: January 2020

PurposeThe risks of natural hazards such as flooding, earthquakes, tsunami, landslides, tornado, coastal erosion and volcano are apparent in Auckland because of its vulnerability to multiple risks. The coping capacity of individuals serves as a precursor to the adaptation to inherent challenges. The purpose of this paper was to examine the coping capacity of the South African community in Auckland to a disaster event.Design/methodology/approachThis study gathered information from both primary and secondary sources. Interviews and survey were the main sources of primary data. The research used parametric and non-parametric statistical tools for quantitative data analysis, and the general inductive process and a three-step coding process to analyse qualitative data. The research findings are discussed in line with existing studies.FindingsThe results indicated that the aggregate coping capacity of the community was above average on the scale of 1-5 with communication and economic domains having the highest and least capacities, respectively. An improvement in disaster response activities and economic ability among the vulnerable population should be considered in future policy to enhance coping capacity.Research limitations/implicationsThe study was limited to the time of the investigation. The practical coping capacity of the community during challenges will be determined. This study excludes the roles of institutions and the natural environment in coping capacity because the unit of analysis was the individual members of the community.Originality/valueThe research is a pioneer study on the coping capacity of the South African community in Auckland.