bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial cells exposed to phosphate and indoxyl sulphate promote vascular calcification through interleukin-8 secretion
Authors: Bouabdallah Jeanne , Zibara Kazem , Issa Hawraa , Lenglet Gaëlle , Kchour Ghada , Caus Thierry , Six Isabelle , Choukroun Gabriel , Kamel Saïd , Bennis Youssef 
Published: September 2018

AbstractBackgroundVascular calcification (VC) is amplified during chronic kidney disease, partly due to uraemic toxins such as inorganic phosphate (Pi) and indoxyl sulphate (IS) that trigger osteogenic differentiation of vascular smooth muscle cells (VSMCs). These toxins also alter endothelial cell (EC) functions but whether this contributes to VC is unknown. Here, we hypothesized that ECs exposed to Pi and IS promote VSMC calcification.MethodsHuman umbilical vein ECs were treated with Pi, IS or both, and then the conditioned media [endothelial cell conditioned medium (EC-CM)] was collected. Human aortic SMCs (HASMCs) were exposed to the same toxins, with or without EC-CM, and then calcification and osteogenic differentiation were evaluated. Procalcifying factors secreted from ECs in response to Pi and IS were screened. Rat aortic rings were isolated to assess Pi+IS-induced calcification at the tissue level.ResultsPi and Pi+IS induced HASMCs calcification, which was significantly exacerbated by EC-CM. Pi+IS induced the expression and secretion of interleukin-8 (IL-8) from ECs. While IL-8 treatment of HASMCs stimulated the Pi+IS-induced calcification in a concentration-dependent manner, IL-8 neutralizing antibody, IL-8 receptors antagonist or silencing IL-8 gene expression in ECs before collecting EC-CM significantly prevented the EC-CM procalcifying effect. IL-8 did not promote the Pi+IS-induced osteogenic differentiation of HASMCs but prevented the induction of osteopontin (OPN), a potent calcification inhibitor. In rat aortic rings, IS also promoted Pi-induced calcification and stimulated the expression of IL-8 homologues. Interestingly, in the Pi+IS condition, IL-8 receptor antagonist lifted the inhibition of OPN expression and partially prevented aortic calcification.ConclusionThese results highlight a novel role of IL-8, whose contribution to VC in the uraemic state results at least from interaction between ECs and VSMCs.
Information Sharing, Holdup, and External Finance: Evidence from Private Firms
Authors: Bird Andrew , Karolyi Stephen A , Ruchti Thomas G 
Published: September 2018

Abstract
To mitigate holdup by an informed incumbent lender, a private borrower may publicly share information in order to increase lender competition. Despite proprietary costs, a subset of private borrowers voluntarily share private information in loan and credit underwriting agreements. These borrowers switch lenders at a 16% higher rate and receive lower loan financing costs. For private firms that go public, we analyze changes in the net benefits of information sharing and study the potential estimation bias from unobservable borrower quality. This setting corroborates our inference that voluntary information sharing reduces lender holdup and alleviates financial constraints for private firms.
Received May 25, 2017; editorial decision August 8, 2018 by Editor David Denis.
Genomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating lineages
Authors: Beale Mathew A. , Marks Michael , Sahi Sharon K. , Tantalo Lauren C. , Nori Achyuta V. , French Patrick , Lukehart Sheila A. , Marra Christina M. , Thomson Nicholas R. 
Published: September 2018

AbstractSyphilis is a sexually transmitted infection caused byTreponema pallidumsubspeciespallidumand may lead to severe complications. Recent years have seen striking increases in syphilis in many countries. Previous analyses have suggested one lineage of syphilis, SS14, may have expanded recently, indicating emergence of a single pandemic azithromycin-resistant cluster. We used direct sequencing ofT. pallidumcombined with phylogenomic analyses to show that both SS14- and Nichols-lineages are simultaneously circulating in clinically relevant populations in multiple countries. We correlate the appearance of genotypic macrolide resistance with multiple independently evolved SS14 sub-lineages and show that genotypically resistant and sensitive sub-lineages are spreading contemporaneously, incompatible with the notion that SS14-lineage expansion is driven purely by macrolide resistance. These findings inform our understanding of the current syphilis epidemic by demonstrating how macrolide resistance evolves inTreponemasubspecies and provide a warning on broader issues of antimicrobial resistance.
Predicting evolution using frequency-dependent selection in bacterial populations
Authors: Azarian Taj , Martinez Pamela P , Arnold Brian J , Grant Lindsay R , Corander Jukka , Fraser Christophe , Croucher Nicholas J , Hammitt Laura L , Reid Raymond , Santosham Mathuram , Weatherholtz Robert C , Bentley Stephen D , O’Brien Katherine L , Lipsitch Marc , Hanage William P 
Published: September 2018

AbstractPredicting how pathogen populations will change over time is challenging. Such has been the case with Streptococcus pneumoniae, an important human pathogen, and the pneumococcal conjugate vaccines (PCVs), which target only a fraction of the strains in the population. Here, we use the frequencies of accessory genes to predict changes in the pneumococcal population after vaccination, hypothesizing that these frequencies reflect negative frequency-dependent selection (NFDS) on the gene products. We find that the standardized predicted fitness of a strain estimated by an NFDS-based model at the time the vaccine is introduced enables to predict whether the strain increases or decreases in prevalence following vaccination. Further, we are able to forecast the equilibrium post-vaccine population composition and assess the invasion capacity of emerging lineages. Overall, we provide a method for predicting the impact of an intervention on pneumococcal populations with potential application to other bacterial pathogens in which NFDS is a driving force.
Population Structure of Leishmania using POPSICLE reveals extensive dichotomy in zygosity and discloses the role of sex in diversity of the parasite
Authors: Shaik Jahangheer S. 
Published: September 2018

AbstractMosaic aneuploidy prevalent in organisms such as Leishmania and Fungi and in genomes of some neurological disorders and cancers manifest as non-integer haplotypes due to heterogeneity in somy across a population of cells. Thus, the tools designed for strictly haploid or diploid genomes are insufficient to study them. We addressed this issue by upgrading our population genetics tool POPSICLE for aneuploid genomes and studied the population structure of 50 strains of Leishmania to understand genetic diversity and the sexual strategies that predispose to that diversity. Leishmania showed enormous diversity but a dichotomic nature of extreme zygosities. To understand this dichotomy, we specifically studied two species, L. tropica that contained strains with both hetero and homozygosities and L. major that were mainly homozygous. The homozygosity in L. tropica was a consequence of extreme inbreeding while heterozygosity was due to recent hybridizations involving two different genotypes. In contrast, L. major also contained two different genotypes and products of extreme inbreeding but no recent hybridizations. The heterozygous strains of L. tropica that were geographically isolated from the homozygous strains were F1 hybrids that appeared sterile to each other while those in proximity to the homozygous strains were outcrosses involving multiple cycles of hybridization indicating their mating preference with homozygous strains. Development of POPSICLE for aneuploid genomes offers a unique tool for determining the shared ancestries and in reinforcing sex as one of the driving mechanisms for speciation as demonstrated for Leishmania. POPSICLE is a Java based utility available for free download at https://popsicle-admixture.sourceforge.io/
Host defense triggers rapid adaptive radiation in experimentally evolving parasites
Authors: Bush Sarah E. , Villa Scott M. , Altuna Juan C. , Johnson Kevin P. , Shapiro Michael D. , Clayton Dale H. 
Published: September 2018

ABSTRACTAdaptive radiation occurs when the members of a single lineage evolve different adaptive forms in response to selection imposed by competitors or predators. Iconic examples include Darwin’s finches, Caribbean anoles, and Hawaiian silverswords, all of which live on islands. Parasites, which live on host “islands,” show macroevolutionary patterns consistent with adaptive radiation in response to host-imposed selection. Here we show rapid adaptive divergence of experimentally evolving feather lice in response to preening, the main host defense. We demonstrate that host defense exerts strong phenotypic selection for crypsis in lice transferred to different colored rock pigeons (Columba livia). During four years of experimental evolution (∼60 generations), the lice evolved heritable differences in color. The color differences spanned the phenotypic distribution of congeneric species of lice adapted to other species of pigeons. Our results indicate that host-mediated selection triggers rapid divergence in the adaptive radiation of parasites, which are among the most diverse organisms on earth. Our research suggests that host defense should be included with competition and predation as a major mechanism driving the evolution of biodiversity by adaptive radiation.
High-glucose Induces Retinal Pigment Epithelium Mitochondrial Pathways of Apoptosis and Inhibits Mitophagy by Regulating ROS/PINK1/Parkin Signal Pathway
Authors: Zhang Yuanping , Xi Xiaoting , Mei Yan , Zhao Xueying , Zhou Liqiong , Ma Minjun , Liu Sili , Zha Xu , Yang Yanni 
Published: September 2018

AbstractDiabetic retinopathy (DR) caused visual performance degradation seriously endangers human beings’ health, uncovering the underlying mechanism might shed light on the discovery of DR therapeutic treatments. In this study, we found that the effects of glucose on retinal pigment epithelium (RPE) varies in a dose dependent manner, high-glucose promotes ROS generation and cell apoptosis, inhibits mitophagy as well as proliferative abilities, while low-glucose induces ROS production and cell mitophagy, but has little impacts on cell apoptosis and proliferation. Of note, the toxic effects of high-glucose on RPE are alleviated by ROS scavengers and aggravated by autophagy inhibitor 3-methyladenine (3-MA) or mitophagy inhibitor cyclosporin A (CsA). High-glucose induced ROS generation is merely eliminated by ROS scavengers instead of mitophagy or autophagy inhibitor. We also proved that high-glucose inhibits cell proliferation and promotes cell apoptosis by regulating ROS mediated inhibition of mitophagy. In addition, mitophagy associated proteins PINK1 and Parkin are downregulated by high-glucose or hydrogen peroxide treatments, which are reversed by ROS scavengers. Of note, Knock-down of PINK1 decreases phospharylated Parkin instead of total Parkin levels in RPE. Intriguingly, high-glucose’s inhibiting effects on cell mitophagy as well as proliferation and its promoting effects on cell apoptosis are reversed by either PINK1 or Parkin overexpression. Therefore, we concluded that high-glucose promotes RPE apoptosis and inhibits cell proliferation as well as mitophagy by regulating oxidative stress mediated inactivation of ROS/PINKl/Parkin signal pathway.
Ozone Treatment for Elimination of Bacteria and SARS-CoV-2 for Medical Environments
Authors: Westover Craig , Rahmatulloev Savlatjon , Danko David , Afshinnekoo Ebrahim , O’Hara Niamh B. , Ounit Rachid , Bezdan Daniela , Mason Christopher E. 
Published: September 2018

AbstractPathogenic bacteria and viruses in medical environments can lead to treatment complications and hospital-acquired infections (HAIs), and current cleaning protocols do not address hard-to-access areas or that may be beyond line-of-sight treatment such as with ultraviolet radiation. At the time of writing, the ongoing pandemic of the novel coronavirus known as novel coronavirus (2019-nCoV) has claimed over 4 million cases worldwide and is expected to have multiple peaks, with possible resurgences throughout 2020. It is therefore imperative that disinfection methods in the meantime be employed to keep up with the supply of personal protective equipment (PPE) and sterilize a wide array of surfaces as quarantine lockdowns begin to be lifted.Here, we tested the efficacy of Sani Sport ozone devices as a means to treat hospital equipment and surfaces for killing bacteria, degrading synthetic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, and RNA from non-replicative capsid enclosed SARS-CoV-2. We observed a rapid killing of medically-relevant and environmental bacteria (Escherichia coli, Enterococcus faecalis, Bacillus subtlis, and Deinococcus radiodurans) across four surfaces (blankets, catheter, remotes, and syringes) within 30 minutes, and up to a 99% reduction in viable bacteria at the end of 2-hour treatment cycles. Significant RNA degradation of synthetic SARS-CoV-2 RNA was seen an hour into the ozone treatment as compared to non-treated controls and a non-replicative form of the virus was shown to have significant RNA degradation at 30 minutes compared to a no treatment control and RNA degradation could be reliably detected at 10,000 and 1,000 copies of virus per sample. These results show the strong promise of ozone treatment for reducing risk of infection and HAIs.
Sfp1 regulates transcriptional networks driving cell growth and division through multiple promoter binding modes
Authors: Albert Benjamin , Tomassetti Susanna , Gloor Yvonne , Dilg Daniel , Mattarocci Stefano , Kubik Slawomir , Shore David 
Published: September 2018

AbstractUnderstanding how transcriptional programs help to coordinate cell growth and division is an important unresolved problem. Here we report that the nutrient-and stress-regulated transcription factor Sfp1 is rate-limiting for expression of several large classes of genes involved in yeast cell growth, including ribosomal protein, ribosome biogenesis, and snoRNA genes. Remarkably, the spectrum of Sfp1 transcription effects is concordant with a combination of chromatin immunoprecipitation and chromatin endogenous cleavage binding analyses, which together provide evidence for two distinct modes of Sfp1 promoter binding, one requiring a co-factor and the other a specific DNA-recognition motif. In addition to growth-related genes, Sfp1 binds to and regulates the promoters of cell cycle “START” regulon genes, including the key G1/S cyclinsCLN1andCLN2. Our findings suggest that Sfp1 acts as a master regulator of cell growth and cell size by coordinating the expression of genes implicated in mass accumulation and cell division.
Polyacrylamide Bead Sensors forin vivoQuantification of Cell-Scale Stress in Zebrafish Development
Authors: Träber N. , Uhlmann K. , Girardo S. , Kesavan G. , Wagner K. , Friedrichs J. , Goswami R. , Bai K. , Brand M. , Werner C. , Balzani D. , Guck J. 
Published: September 2018

ABSTRACTMechanical stress exerted and experienced by cells during tissue morphogenesis and organ formation plays an important role in embryonic development. While techniques to quantify mechanical stressesin vitroare available, few methods exist for studying stresses in living organisms. Here, we describe and characterize cell-like polyacrylamide (PAAm) bead sensors with well-defined elastic properties and size forin vivoquantification of cell-scale stresses. The beads were injected into developing zebrafish embryos and their deformations were computationally analyzed to delineate spatio-temporal local acting stresses. With this computational analysis-based cell-scale stress sensing (COMPAX) we are able to detect pulsatile pressure propagation in the developing neural rod potentially originating from polarized midline cell divisions and continuous tissue flow. COMPAX is expected to provide novel spatiotemporal insight into developmental processes at the local tissue level and to facilitate quantitative investigation and a better understanding of morphogenetic processes.
Signaling incentive and drive in the primate ventral pallidum for motivational control of goal-directed action
Authors: Fujimoto Atsushi , Hori Yukiko , Nagai Yuji , Kikuchi Erika , Oyama Kei , Suhara Tetsuya , Minamimoto Takafumi 
Published: September 2018

AbstractProcessing incentive and drive is essential for control of goal-directed behavior. The limbic part of the basal ganglia has been emphasized in these processes, yet the exact neuronal mechanism has remained elusive. In this study, we examined the neuronal activity of the ventral pallidum (VP) and its upstream area, the rostromedial caudate (rmCD), while two male macaque monkeys performed an instrumental lever-release task, in which a visual cue indicated the forthcoming reward size. We found that the activity of some neurons in VP and rmCD reflected the expected reward-size transiently following the cue. Reward-size coding appeared earlier and stronger in VP than in rmCD. We also found that the activity in these areas was modulated by the satiation level of monkeys, which also occurred more frequently in VP than in rmCD. The information regarding reward-size and satiation-level was independently signaled in the neuronal populations of these areas. The data thus highlighted the neuronal coding of key variables for goal-directed behavior in VP. Furthermore, pharmacological inactivation of VP induced more severe deficit of goal-directed behavior than inactivation of rmCD, which was indicated by abnormal error repetition and diminished satiation effect on the performance. These results suggest that VP encodes incentive value and internal drive, and plays a pivotal role in the control of motivation to promote goal-directed behavior.Significance StatementThe limbic part of the basal ganglia has been emphasized in the motivational control of goal-directed action. Here, we investigated how the ventral pallidum (VP) and the rostromedial caudate (rmCD) encode incentive value and internal drive, and control goal-directed behavior. Neuronal recording and subsequent pharmacological inactivation revealed that VP had stronger coding of reward size and satiation level than rmCD. Reward size and satiation level were independently encoded in the neuronal population of these areas. Furthermore, VP inactivation impaired goal-directed behavior more severely than rmCD inactivation. These results highlighted the central role of VP in the motivational control of goal-directed action.
ProTargetMiner: A proteome signature library of anticancer molecules for functional discovery
Authors: Saei Amir Ata , Chernobrovkin Alexey , Sabatier Pierre , Zhang Bo , Beusch Christian , Tokat Ülkü Güler , Gaetani Massimiliano , Végvári Ákos , Zubarev Roman A. 
Published: September 2018

AbstractWe present a publicly available, expandable proteome signature library of anticancer molecules in A549 adenocarcinoma cells. Based on 287 proteomes affected by 56 drugs, the main dataset contains 7,328 proteins and 1,307,859 refined protein-drug pairs. By employing the specificity concept in partial least square modeling, deconvolution of drug targets and mechanistic proteins is achieved for most compounds, including some kinase inhibitors. We built the first protein co-regulation database that takes into account both protein expression and degradation. A surprising number of strong anti-correlations is found, underscoring the importance of protein repression in cell regulation. Our analysis uncovered a group of proteins with extremely steady expression which are likely essential for core cellular functions. These findings bring about deeper understanding of cell mechanics. Extension of the dataset to novel compounds will facilitate drug design. The introduced specificity concept and modeling scheme are beneficial in other analysis types as well.Statement of SignificanceProTargetMiner is the first of its kind library of proteome responses of human cancer cells to anticancer molecules. This expandable resource facilitates the deconvolution of drug targets, action mechanisms, and cellular effects. It reveals death modalities, uncovers protein co-regulation and anti-correlation networks and defines the “untouchable” proteome essential for core cellular functionalities.
RELION-3: new tools for automated high-resolution cryo-EM structure determination
Authors: Zivanov Jasenko , Nakane Takanori , Forsberg Björn , Kimanius Dari , Hagen Wim J.H. , Lindahl Erik , Scheres Sjors H.W. 
Published: September 2018

AbstractHere, we describe the third major release of relion. CPU-based vector acceleration has been added in addition to GPU support, which provides flexibility in use of resources and avoids memory limitations. Reference-free autopicking with Laplacian-of-Gaussian filtering and execution of jobs from python allows non-interactive processing during acquisition, including 2D-classification, de novo model generation and 3D-classification. Perparticle refinement of CTF parameters and correction of estimated beam tilt provides higher-resolution reconstructions when particles are at different heights in the ice, and/or coma-free alignment has not been optimal. Ewald sphere curvature correction improves resolution for large particles. We illustrate these developments with publicly available data sets: together with a Bayesian approach to beam-induced motion correction it leads to resolution improvements of 0.2-0.7 Å compared to previous relion versions.
The GATOR complex regulates an essential response to meiotic double-stranded breaks inDrosophila
Authors: Wei Youheng , Bettedi Lucia , Kim Kuikwon , Ting Chun-Yuan , Lilly Mary A. 
Published: September 2018

AbstractThe TORC1 inhibitor GATOR1/SEACIT controls meiotic entry and early meiotic events in yeast. However, how metabolic pathways influence meiotic progression in metazoans remains poorly understood. Here we report that the TORC1 regulators GATOR1 and GATOR2 mediate a response to meiotic double-stranded breaks (DSBs) duringDrosophilaoogenesis. We find that meiotic DSBs trigger the activation of a GATOR1 dependent pathway that downregulates TORC1 activity in the female germline. In GATOR1 mutants, high TORC1 activity results in the delayed repair of meiotic DSBs and the hyperactivation of p53. Conversely, the GATOR2 component Mio is required to attenuate GATOR1 activity, to ensure that meiotic DSBs do not trigger a permanent growth arrest. Unexpectedly, we found that GATOR1 inhibits retrotransposon expression in the presence of meiotic DSBs in a pathway that functions in parallel to p53. Our studies have revealed a link between the GATOR complex, the repair of meiotic DSBs and retrotransposon expression
Temporal resolution of single photon responses in primate rod photoreceptors and limits imposed by cellular noise
Authors: Field Greg D. , Uzzell Valerie , Chichilnisky E.J. , Rieke Fred 
Published: September 2018

SummarySensory receptor noise corrupts sensory signals, contributing to imperfect perception and dictating central processing strategies. For example, noise in rod phototransduction limits our ability to detect light and minimizing the impact of this noise requires precisely tuned nonlinear processing by the retina. But detection sensitivity is only one aspect of night vision: prompt and accurate behavior also requires that rods reliably encode the timing of photon arrivals. We show here that the temporal resolution of responses of primate rods is much finer than the duration of the light response and identify the key limiting sources of transduction noise. We also find that the thermal activation rate of rhodopsin is lower than previous estimates, implying that other noise sources are more important than previously appreciated. A model of rod single-photon responses reveals that the limiting noise relevant for behavior depends critically on how rod signals are pooled by downstream neurons.