bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circadian protein regulation in the green lineage I. A phospho-dawn of protein modification anticipates light onset in the picoeukaryoteO. tauri
Authors: Noordally Zeenat B. , Hindle Matthew M. , Martin Sarah F. , Seaton Daniel D. , Simpson T. Ian , Bihan Thierry Le , Millar Andrew J. 
Published: April 2018

AbstractDiel regulation of protein levels and protein modification had been less studied than transcript rhythms. Here, we compare transcriptome data under light-dark cycles to partial proteome and phosphoproteome data, assayed using shotgun mass-spectrometry, from the algaOstreococcus tauri, the smallest free-living eukaryote. 10% of quantified proteins but two-thirds of phosphoproteins were rhythmic. Mathematical modelling showed that light-stimulated protein synthesis can account for the observed clustering of protein peaks in the daytime. Prompted by night-peaking and apparently dark-stable proteins, we also tested cultures under prolonged darkness, where the proteome changed less than under the diel cycle. The dark-stable, prasinophyte-specific proteins were also reported to accumulate whenO. tauriformed lipid droplets. In the phosphoproteome, 39% of rhythmic phospho-sites reached peak levels just before dawn. This anticipatory phosphorylation suggests that a clock-regulated phospho-dawn prepares green cells for daytime functions. Acid-directed and proline-directed protein phosphorylation sites were regulated in antiphase, implicating the clock-related, casein kinases 1 and 2 in phase-specific regulation, alternating with the CMGC protein kinase family. Understanding the dynamic phosphoprotein network should be facilitated by the minimal kinome and proteome ofO. tauri. The data are available from ProteomeXchange, with identifiers PXD001734, PXD001735 and PXD002909. This submission updates a previous version, posted on bioRxiv on 4th April 2018, ashttps://www.biorxiv.org/content/10.1101/287862v1HighlightThe phosphorylation of most protein sites was rhythmic under light-dark cycles, and suggested circadian control by particular kinases. Day-peaking, rhythmic proteins likely reflect light-stimulated protein synthesis in this microalga.
Pre-saccadic remapping relies on dynamics of spatial attention
Authors: Szinte Martin , Jonikaitis Donatas , Rangelov Dragan , Deubel Heiner 
Published: April 2018

SummaryEach eye movement shifts the projections of the visual scene on the retina. It has been proposed that the receptive fields of neurons in oculomotor areas are remapped pre-saccadically to account for these shifts. While remapping of the whole visual scene seems prohibitively complex, selection by visual attention may limit these processes to a subset of attended locations. Because attentional selection consumes time, remapping of attended locations should evolve in time, too. In our study, we cued a spatial location by presenting an attention capturing cue at different times before a saccade and constructed detailed maps of attentional allocation across the visual field. We observed no remapping when the cue appeared shortly before saccade. In contrast, when the cue appeared sufficiently early before saccade, attentional resources were reallocated to the remapped location. Our results suggest that pre-saccadic remapping is an attentional process relying on the spatial and temporal dynamics of visual attention.
The Influence Of Social Behavior On Competition Between Virulent Pathogen Strains
Authors: Pharaon Joe , Bauch Chris T. 
Published: April 2018

1AbstractInfectious disease interventions like contact precautions and vaccination have proven effective in disease control and elimination. The priority given to interventions can depend strongly on how virulent the pathogen is, and interventions may also depend partly for their success on social processes that respond adaptively to disease dynamics. However, mathematical models of competition between pathogen strains with differing natural history profiles typically assume that human behaviour is fixed. Here, our objective is to model the influence of social behaviour on the competition between pathogen strains with differing virulence. We couple a compartmental Susceptible-Infectious-Recovered model for a resident pathogen strain and a mutant strain with higher virulence, with a differential equation of a population where individuals learn to adopt protective behaviour from others according to the prevalence of infection of the two strains and the perceived severity of the respective strains in the population. We perform invasion analysis, time series analysis and phase plane analysis to show that perceived severities of pathogen strains and the efficacy of infection control against them can greatly impact the invasion of more virulent strain. We demonstrate that adaptive social behaviour enables invasion of the mutant strain under plausible epidemiological scenarios, even when the mutant strain has a lower basic reproductive number than the resident strain. Surprisingly, in some situations, increasing the perceived severity of the resident strain can facilitate invasion of the more virulent mutant strain. Our results demonstrate that for certain applications, it may be necessary to include adaptive social behaviour in models of the emergence of virulent pathogens, so that the models can better assist public health efforts to control infectious diseases.
Predicting humoral alloimmunity from differences in donor-recipient HLA surface electrostatic potential
Authors: Mallon Dermot H , Kling Christiane , Robb Matthew , Ellinghaus Eva , Bradley J Andrew , Taylor Craig J , Kabelitz Dieter , Kosmoliaptsis Vasilis 
Published: April 2018

AbstractIn transplantation, development of humoral alloimmunity against donor HLA is a major cause of organ transplant failure but our ability to assess the immunological risk associated with a potential donor-recipient HLA combination is limited. We hypothesised that the capacity of donor HLA to induce a specific alloantibody response depends on their structural and physicochemical dissimilarity compared to recipient HLA. To test this hypothesis, we first developed a novel computational scoring system that enables quantitative assessment of surface electrostatic potential differences between donor and recipient HLA molecules at the tertiary structure level (electrostatic mismatch score-three dimensional; EMS-3D). We then examined humoral alloimmune responses in healthy females subjected to a standardised injection of donor lymphocytes from their male partner. This analysis showed a strong association between the EMS-3D of donor HLA and donor-specific alloantibody development; this relationship was strongest for HLA-DQ alloantigens. In the clinical transplantation setting, the immunogenic potential of HLA-DRB1 and -DQ mismatches expressed on donor kidneys, as assessed by their EMS-3D, was an independent predictor of development of donor-specific alloantibody after graft failure. Collectively, these findings demonstrate the translational potential of our approach to improve immunological risk assessment and to decrease the burden of humoral alloimmunity in organ transplantation.
The solvent-excluded surfaces of water-soluble proteins
Authors: Wang Lincong 
Published: April 2018

AbstractThe solvent-excluded surface (SES) of a protein is determined by and in turn affects protein-solvent interaction and consequently plays important roles in its solvation, folding and function. However, accurate quantitative relationships between them remain largely unknown at present. To evaluate SES’s contribution to protein-solvent interaction we have applied our accurate and robust SES computation algorithm to various sets of proteins and ligand-protein interfaces. Our results show that each of the analyzed water-soluble proteins has a negative net charge on its SES. In addition we have identified a list of SES-defined physical and geometrical properties that likely pertain to protein solvation and folding based on their characteristic changes with protein size, their differences between folded and extended conformations, and their correlations with known hydrophobicity scales and with experimentally-determined protein solubility. The relevance of the list of SES-defined properties to protein structure and function is supported by their differences between water-soluble proteins and transmembrane proteins and between solvent-accessible regions and ligand-binding interfaces. Taken together our analyses reveal the importance of SES for protein solvation, folding and function. In particular the universal enrichment of negative charge and the larger than average SES area for a polar atom on the surface of a water-soluble protein suggest that from a protein-solvent interaction perspective to fold into a native state is to optimize the electrostatic and hydrogen-bonding interactions between solvent molecules and the surface polar atoms of a protein rather than to only minimize its apolar surface area.
An evolutionary transcriptomics approach links CD36 to membrane remodeling in replicative senescence
Authors: Saitou Marie , Lizardo Darleny Y. , Taskent Recep Ozgur , Millner Alec , Atilla-Gokcumen Gunes Ekin , Gokcumen Omer 
Published: April 2018

SummaryCellular senescence, the irreversible ceasing of cell division, has been associated with organismal aging, prevention of cancerogenesis, and developmental processes. As such, the evolutionary basis and biological features of cellular senescence remain a fascinating area of research. In this study, we conducted comparative RNAseq experiments to detect genes associated with replicative senescence in two different human cell lines and at different time points. We identified 841 and 900 genes (core senescence-associated genes) that are significantly up- and downregulated in senescent cells, respectively, in both cell lines. Our functional enrichment analysis showed that downregulated core genes are primarily involved in cell cycle processes while upregulated core gene enrichment indicated various lipid-related processes. We further demonstrated that downregulated genes are significantly more conserved than upregulated genes. Using both transcriptomics and genetic variation data, we identified one of the upregulated, lipid metabolism gene, CD36 as an outlier. We found that overexpression of CD36 induces a senescence-like phenotype and, further, the media of CD36-overexpressing cells alone can induce a senescence-like phenotype in proliferating young cells. Moreover, we used a targeted lipidomics approach and showed that phosphatidylcholines accumulate during senescence in these cells, suggesting that upregulation of CD36 could contribute to membrane remodeling during senescence. Overall, these results contribute to the understanding of evolution and biology of cellular senescence and identify several targets and questions for future studies.
Plants with purple abaxial leaves: A repository of metrics from stomata distribution
Authors: de Almeida filho Humberto Antunes , Bruno Odemir Martinez 
Published: April 2018

AbstractPlants with purple abaxial leaves are very common in nature but the ecophysiological aspects of this phenotype are not well known. We observed here that the purple color of the abaxial tegument in extant plants make stomata completely visible. Based in it we measured the relations between stomatic density and distance between stomata pairs and observed a general log-normal trend line between density and interstomatic distance. These data shows that measures of stomatic distances at purple abaxial leaves are able to be a sensor to environmental changes of living purple plants. In future ecophysiological inferences will be established from the information brought by the measurements of the distance between stomata in purple plants.
Fitness effects of altering gene expression noise inSaccharomyces cerevisiae
Authors: Duveau Fabien , Hodgins-Davis Andrea , Metzger Brian P.H. , Yang Bing , Tryban Stephen , Walker Elizabeth A. , Lybrook Patricia , Wittkopp Patricia J. 
Published: April 2018

AbstractGene expression noise is an evolvable property of biological systems that describes differences in gene expression among genetically identical cells in the same environment. Prior work has shown that expression noise is heritable and can be shaped by natural selection, but the impact of variation in expression noise on organismal fitness has proven difficult to measure. Here, we quantify the fitness effects of altering expression noise for theTDH3gene inSaccharomyces cerevisiae. We show that increases in expression noise can be deleterious or beneficial depending on the difference between the average expression level of a genotype and the expression level maximizing fitness. We also show that a simple model relating single-cell expression levels to population growth produces patterns that are consistent with our empirical data. We use this model to explore a broad range of average expression levels and expression noise, providing additional insight into the fitness effects of variation in expression noise.
Myosin-II mediated traction forces evoke localized Piezo1 Ca2+ flickers
Authors: Ellefsen Kyle L. , Holt Jesse R. , Chang Alice , Nourse Jamison L. , Arulmoli Janahan , Mekhdjian Armen , Abuwarda Hamid , Tombola Francesco , Flanagan Lisa A. , Dunn Alexander R. , Parker Ian , Pathak Medha M. 
Published: April 2018

ABSTRACTPiezo channels transduce mechanical stimuli into electrical and chemical signals, and in doing so, powerfully influence development, tissue homeostasis, and regeneration. While much is known about how Piezo1 responds to external forces, its response to internal, cell-generated forces remains poorly understood. Here, using measurements of endogenous Piezo1 activity and traction forces in native cellular conditions, we show that actomyosin-based cellular traction forces generate spatially-restricted Ca2+ flickers in the absence of externally-applied mechanical forces. Although Piezo1 channels diffuse readily in the plasma membrane and are widely distributed across the cell, their flicker activity is enriched in regions proximal to force-producing adhesions. The mechanical force that activates Piezo1 arises from Myosin II phosphorylation by Myosin Light Chain Kinase. We propose that Piezo1 Ca2+ flickers allow spatial segregation of mechanotransduction events, and that diffusion allows channel molecules to efficiently respond to transient, local mechanical stimuli.
metamicrobiomeR: an R package for analysis of microbiome relative abundance data using zero-inflated beta GAMLSS and meta-analysis across studies using random effect models
Authors: Ho Nhan Thi , Li Fan 
Published: April 2018

ABSTRACTBackgroundThe rapid growth of high-throughput sequencing-based microbiome profiling has yielded tremendous insights into human health and physiology. Data generated from high-throughput sequencing of 16S rRNA gene amplicons are often preprocessed into composition or relative abundance. However, reproducibility has been lacking due to the myriad of different experimental and computational approaches taken in these studies. Microbiome studies may report varying results on the same topic, therefore, meta-analyses examining different microbiome studies to provide robust results are important. So far, there is still a lack of implemented methods to properly examine differential relative abundances of microbial taxonomies and to perform meta-analysis examining the heterogeneity and overall effects across microbiome studies.ResultsWe developed an R package ‘metamicrobiomeR’ that applies Generalized Additive Models for Location, Scale and Shape (GAMLSS) with a zero-inflated beta (BEZI) family (GAMLSS-BEZI) for analysis of microbiome relative abundance datasets. Both simulation studies and application to real microbiome data demonstrate that GAMLSS-BEZI well performs in testing differential relative abundances of microbial taxonomies. Importantly, the estimates from GAMLSS-BEZI are log(odds ratio) of relative abundances between groups and thus are comparable between microbiome studies. As such, we also apply random effects meta-analysis models to pool estimates and their standard errors across microbiome studies. We demonstrate the meta-analysis workflow and highlight the utility of our package on four studies comparing gut microbiomes between male and female infants in the first six months of life.ConclusionsGAMLSS-BEZI allows proper examination of microbiome relative abundance data. Random effects meta-analysis models can be directly applied to pool comparable estimates and their standard errors to evaluate the heterogeneity and overall effects across microbiome studies. The examples and workflow using our metamicrobiomeR package are reproducible and applicable for the analyses and meta-analyses of other microbiome studies.
Physiological Characteristics of Viable-but-nonculturableVibrio parahaemolyticusupon Prolonged Exposure to the Refrigerator Temperature
Authors: Yoon Jae-Hyun , Lee Sun-Young 
Published: April 2018

ABSTRACTAlthough it has been reported thatviable-but-nonculturable (VBNC) cells ofVibrio parahaemolyticuscan be developed by a prolonged duration of cold-starvation there are restricted cellular characteristics available on understanding the exact mechanisms governing the entry of pathogens into the VBNC state. Therefore, this research was aimed at determining the cellular profile of VBNC cells ofV. parahaemolyticusupon exposure to the refrigerator temperature. Strains ofV. parahaemolyticuswere incubated in artificial sea water (ASW) microcosms (pH 6) added with different amounts of NaCl at 4°C until these pathogens entered into such a dormant state. At a regular time-interval, both culturability and viability of these bacteria were enumerated, and then cellular profiling were carried out in terms of cellular membrane permeability, enzymatic activity, hydrophobicity, fatty acid composition, and morphological changes after cells ofV. parahaemolyticusbecame the VBNC state. Three strains ofV. parahaemolyticusused in this study showed that VBNC cells retained the strong virulent properties to Vero and CACO-2 cell lines, re-gained the cytotoxicity even after resuscitation, became permeabilized in terms of the outer membrane, showed lower levels of enzymatic (catalase and glutathione-S-transferase) activities, exerted the increasing hydrophobicity, and then exhibited increasing amounts of saturated fatty acids.IMPORTANCETo the current best knowledge, there are restricted information available on understanding the physiological characterization of viable-but-nonculturable cells. Most previous studies are still making a degree of efforts in discovering the causative effector causing microorganisms to be induced into the VBNC state. Herein, the present study showed that pathogenicV. parahaemolyticuscan enter into the VBNC state when challenged by a certain environmental stress where higher amounts of NaCl combined with acidic pHs was artificially controlled. Importantly, it was indicated that VBNCV. parahaemolyticusmaintained peculiarly different physiological characteristics. Furthermore, this study proposed a novel approach on the transient/stepwise conversion of the bacteria into the VBNC state. Specific alternative tools for measuring and controlling the incidence of VBNC pathogens on food are not established until now. In this aspect, results obtained from this study will used to provide an effective insight in determining physiological properties of viable-but-nonculturableV. parahaemolyticus.
Manganese oxide biomineralization is a social trait protecting against nitrite toxicity
Authors: Zerfaß Christian , Christie-Oleza Joseph A. , Soyer Orkun S. 
Published: April 2018

AbstractManganese bio-mineralization by oxidation is a costly but, still, widespread process among bacteria and fungi. While certain potential advantages of manganese oxidation have been suggested, to date there is no conclusive experimental evidence for, how and if this process impacts microbial fitness in the environment. Here we show how a model organism for manganese oxidation,Roseobacter sp.AzwK-3b, is growth-inhibited by nitrite, and that this inhibition is mitigated when manganese is added to the culture medium. We show that manganese-mediated mitigation of nitrite-inhibition is dependent on the culture inoculum size, with larger inocula being able to withstand higher concentrations of nitrite stress. Furthermore, the bio-mineralized manganese oxide (MnOX) forms granular precipitates in the culture, rather than sheaths around individual cells. These findings support the notion that MnOXis a shared community product that improves the cultures’ survival against nitrite-stress. We show that the mechanistic basis of the MnOXeffect involves both its ability to catalyze nitrite oxidation into (non-toxic) nitrate under physiological conditions, and its potential role in influencing redox chemistry around reactive oxygen species (ROS). Taken together, these results provide for the first direct evidence of improved microbial fitness byMnOXdeposition in an ecological setting, i.e. mitigation of nitrite toxicity, and point to a key role of MnOXin handling stresses arising from ROS. These findings could be of generalrelevance for all organisms oxidizing manganese, allowing them to offset costs associated with extracellular bio-mineralization.
Equity financing constraints and R&D investments: evidence from an IPO suspension in China
Authors: Cui Binxi , Yang Chaojun 
Published: April 2018

Purpose
The purpose of this paper is to exploit the effect of equity financing constraints on the firm’s investment in research and development (R&D) by utilizing a quasi-experiment in China.

Design/methodology/approach
A difference-in-difference identification strategy is employed to test the treatment effect of the IPO suspension in China. For robustness testing, the authors incorporate cross-sectional variation in external financial dependence to identify the different influences an IPO suspension has on R&D investments for firms across multiple industries through the difference-in-difference-in-difference approach and the authors also adopt a matching approach to check the parallel trend assumption. Moreover, the authors introduce a placebo test to further verify the empirical results.

Findings
Through the empirical analysis, the authors find that the firms subjecting to the IPO suspension are more likely to reduce their investments in R&D than those not affected by the IPO suspension. Besides, the negative effect of equity financing constraints on R&D investments is concentrated on external financial dependent industries. The firms in industries with larger external financial dependence tend to decrease more in their R&D expenditures when they experience the equity financing constraints.

Research limitations/implications
This paper provides a new negative evidence on equity financing constraints on R&D investments link so that contributes to the debate about the effect of the financing constraints on R&D investments.

Practical implications
The study provides a meaningful suggestion for governments to diminish the frictions in the financial market and to improve enterprises’ public financing circumstances by finding that equity financing constraints have negative impacts on firms’ R&D investments.

Originality/value
There are some apprehensions around previous empirical studies investigating the impact of financing constraints on R&D investments as the existing literature is unable to provide an unambiguous method to exactly distinguish and measure the degree of financing constraints the firms confronting with. This paper solves this problem by first utilizing an IPO suspension in China as a quasi-experiment to examine the effect of equity financing constraints. Therefore, it gives insight to solve the problem of measuring financing constraints in future researches.