bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Microlesions Form During Severe BacteremicEnterococcus faecalisInfection
Authors: Brown Armand O. , Singh Kavindra V. , Cruz Melissa R. , Kaval Karan Gautam , Francisco Liezl E. , Murray Barbara E. , Garsin Danielle A. 
Published: January 2020

AbstractEnterococcus faecalisis a significant cause of hospital-acquired bacteremia. Herein, the discovery is reported that cardiac microlesions form during severe bacteremicE. faecalisinfection in mice. The cardiac microlesions were identical in appearance to those formed byStreptococcus pneumoniaeduring invasive pneumococcal disease (IPD). However,E. faecalisdoes not encode the virulence determinants implicated in pneumococcal microlesion formation. Rather, disulfide bond forming protein DsbA was found to be required forE. faecalisvirulence in aC. elegansmodel and was necessary for efficient cardiac microlesion formation. Furthermore,E. faecalispromoted cardiomyocyte apoptotic and necroptotic cell death at sites of microlesion formation. Additionally, loss of DsbA caused an increase in pro-inflammatory cytokines unlike the wild-type strain, which suppressed the immune response. In conclusion, we establish thatE. faecalisis capable of forming cardiac microlesions and identify features of both the bacterium and the host response that are mechanistically involved.SUMMARYThis work presents the observation of cardiac microlesion formation during severe blood stream infection withEnterococcus faecalisin mice. Moreover, we identify the contribution of a novel enterococcal virulence determinant in modulating microlesion formation and the host immune response.
Bioluminescence dynamics in single germinating bacterial spores reveal metabolic heterogeneity
Authors: Frentz Zak , Dworkin Jonathan 
Published: January 2020

AbstractSpore-forming bacteria modulate their metabolic rate by over 5 orders of magnitude as they transition between dormant spores and vegetative cells, and thus represent an extreme case of phenotypic variation. During environmental changes in nutrient availability, clonal populations of spore-forming bacteria exhibit individual differences in cell fate, timing of phenotypic transitions, and gene expression. One potential source of this variability is metabolic heterogeneity, but this has not yet been measured, as existing single-cell methods are not easily applicable to spores due to their small size and strong autofluorescence. Here, we use the bacterial bioluminescence system and a highly sensitive microscope to measure metabolic dynamics in thousands ofB. subtilisspores as they germinate. We observe and quantitate large variations in the bioluminescence dynamics across individual spores that can be decomposed into contributions from variability in germination timing, the amount of endogenously produced luminescence substrate, and the intracellular reducing power. This work shows that quantitative measurement of spore metabolism is possible and thus it opens venues for future study of the thermodynamic nature of dormant states.
Oxidative stress delays development and alters gene function in the agricultural pest moth,Helicoverpa armigera
Authors: Apirajkamol Nonthakorn (Beatrice) , James Bill , Walsh Tom K , McGaughran Angela 
Published: January 2020

AbstractStress is a widespread phenomenon that all organisms must endure. Common in nature is oxidative stress, which can interrupt cell homeostasis to cause cell damage and may be derived from respiration or from environmental exposure thought diet. As a result of the routine exposure from respiration, many organisms can mitigate the effects of oxidative stress, but less is known about responses to oxidative stress from other sources.Helicoverpa armigerais a major agricultural pest moth that causes significant damage to crops worldwide. Here, we examined the effects of oxidative stress onH. armigeraby chronically exposing individuals to paraquat - a free radical producer - and measuring changes in development (weight, developmental rate, lifespan), and gene expression.We found that oxidative stress strongly affected development inH. armigera, with stressed samples spending more time as caterpillars than control samples (>24 vs. ∼15 days, respectively) and living longer overall. We found 1,618 up- and 761 down-regulated genes, respectively, in stressed vs. control samples. In the up-regulated gene set were genes associated with cell senescence and apoptosis and an over-representation of biological processes related to cuticle and chitin development, glycine metabolism, and oxidation-reduction.Oxidative stress clearly impacts physiology and biochemistry inH. armigeraand the interesting finding of an extended lifespan in stressed individuals could demonstrate hormesis, the process whereby toxic compounds can actually be beneficial at low doses. Collectively, our findings provide new insights into genomic responses to oxidative stress in invertebrates.
Synthesis of geological and comparative phylogeographic data point to climate, not mountain uplift, as driver of divergence across the Eastern Andean Cordillera
Authors: Rodríguez-Muñoz Erika , Montes Camilo , Crawford Andrew J. 
Published: January 2020

AbstractAimTo evaluate the potential role of the orogeny of the Eastern Cordillera (EC) of the Colombian Andes and the Mérida Andes (MA) of Venezuela as drivers of vicariance between populations of 37 tetrapod lineages co-distributed on both flanks, through geological reconstruction and comparative phylogeographic analyses.LocationNorthwestern South AmericaMethodsWe first reviewed and synthesized published geological data on the timing of uplift for the EC-MA. We then combined newly generated mitochondrial DNA sequence data with published datasets to create a comparative phylogeographic dataset for 37 independent tetrapod lineages. We reconstructed time-calibrated molecular phylogenies for each lineage under Bayesian inference to estimate divergence times between lineages located East and West of the Andes. We performed a comparative phylogeographic analysis of all lineages within each class of tetrapod using hierarchical approximate Bayesian computation (hABC) to test for synchronous vicariance across the EC-MA. To evaluate the potential role of life history in explaining variation in divergence times among lineages, we evaluated 13 general linear models (GLM) containing up to six variables each (maximum elevation, range size, body length, thermoregulation, type of dispersal, and taxonomic class).ResultsOur synthesis of geological evidence suggested that the EC-MA reached significant heights by 38–33 million years ago (Ma) along most of its length, and we reject the oft-cited date of 2–5 Ma. Based on mtDNA divergence from 37 lineages, however, the median estimated divergence time across the EC-MA was 3.26 Ma (SE = 2.84) in amphibians, 2.58 Ma (SE = 1.81) in birds, 2.99 Ma (SE = 4.68) in reptiles and 1.43 Ma (SE = 1.23) in mammals. Using Bayes Factors, the hypothesis for a single temporal divergence interval containing synchronous divergence events was supported for mammals and but not supported for amphibians, non-avian reptiles, or birds. Among the six life-history variables tested, only thermoregulation successfully explained variation in divergence times (minimum AICc,R20.10), with homeotherms showing more recent divergence relative to poikilotherms.Main conclusionsOur results reject the hypothesis of the rise Andean Cordillera as driver of vicariance of lowland population because divergence dates are too recent and too asynchronous. We discuss alternative explanations, including dispersal through mountain passes, and suggest that changes in the climatic conditions during the Pliocene and Pleistocene interacted with tetrapod physiology, promoting older divergences in amphibians and reptiles relative to mammals and birds on an already established orogen.
What drives male association tendencies in wild zebrafish? Role of female and vegetation densities
Authors: Ghoshal Aditya , Bhat Anuradha 
Published: January 2020

AbstractMating strategies in species is context-dependent and driven by several ecological and demographic factors. In natural habitats, a multitude of ecological factors interact and these eventually determine mating preferences and mate choice decisions among species. While zebrafish (Danio rerio) is a widely studied biological model organism, our understanding of their mating preferences, strategies and their underlying ecological drivers are still limited. Here, we explore the role of ecological factors such as spatial variation (or patchiness) in mate density and associated vegetation cover in determining mate association tactics among males in a wild zebrafish population. We employed a multi-choice experimental design for a better representation of ecologically relevant scenarios. Our results revealed that when presented with patches with increasing female densities, males displayed only a marginal increase in preference for higher female density patches. However, when female density varied concomitantly with variation in vegetation cover, the males associated more with higher foliage density patches irrespective of the female density in that patch. Our findings throw light on the complex interaction between these two most basic ecological factors in determining mate search strategies and mate associations among these group-living fish species.
Iron and Lipocalin-2 Modulate Cellular Responses in the Tumor Micro-environment of Pancreatic Ductal Adenocarcinoma
Authors: Pita-Grisanti Valentina , Dangel Andrew W. , Gumpper Kristyn , Ludwig Andrea , Ueltschi Olivia , Mo Xiaokui , Pietrzak Maciej , Webb Amy , Hwang Rosa F. , Traczek Madelyn , Badi Niharika , Cruz-Monserrate Zobeida 
Published: January 2020

AbstractPancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with poor outcomes. Iron is known to signal cellular responses, and its levels are regulated by lipocalin-2 (LCN2) expression, a PDAC pro-tumorigenic molecule. However, how iron and LCN2 function in PDAC is unclear. Here we demonstrate that iron levels regulate PDAC cell proliferation, invasion, expression of epithelial to mesenchymal tumor markers, and pro-inflammatory cytokines. Iron chelation increased the expression of the LCN2 receptorSLC22A17in pancreatic stellate cells and the anti-metastatic geneNDRG1in PDAC cells. Deletion ofLcn2in mouse tumor cells modulated the expression of genes involved in extracellular matrix deposition and cell migration. Moreover, cellular iron responses were dependent on theKrasmutation status of cells, andLCN2expression levels. Deletion ofLcn2expression in PDAC suggests a protective role against metastasis. Thus, iron modulation and LCN2 blockade could serve as potential therapeutic approaches against PDAC.
Quantifying the impact of Human Leukocyte Antigen on the human gut microbiome
Authors: Andeweg Stijn P. , Keşmir Can , Dutilh Bas E. 
Published: January 2020

AbstractObjectiveThe gut microbiome is affected by a number of factors, including the innate and adaptive immune system. The major histocompatibility complex (MHC), or the human leukocyte antigen (HLA) in humans, performs an essential role in vertebrate immunity, and is very polymorphic in different populations. HLA determines the specificity of T lymphocyte and natural killer (NK) cell responses, including against the commensal bacteria present in the human gut. Thus, it is likely that our HLA molecules and thereby the adaptive immune response, can shape the composition of our microbiome. Here, we investigated the effect of HLA haplotype on the microbiome composition.ResultsWe performed HLA typing and microbiota composition analyses on 3,002 public human gut microbiome datasets. We found that (i) individuals with functionally similar HLA molecules (i.e. presenting similar peptides) are also similar in their microbiota, and (ii) HLA homozygosity correlated with microbiome diversity, suggesting that diverse immune responses limit microbiome diversity.ConclusionOur results show a statistical association between host HLA haplotype and gut microbiome composition. Because the HLA haplotype is a readily measurable parameter of the human immune system, these results open the door to incorporating the immune system into predictive microbiome models.IMPORTANCEThe microorganisms that live in the digestive tracts of humans, known as the gut microbiome, are essential for hosts survival as they support crucial functions. For example, they support the host in facilitating the uptake of nutrients and give colonization resistance against pathogens. The composition of the gut microbiome varies among humans. Studies have proposed multiple factors driving the observed variation, including; diet, lifestyle, and health condition. Another major influence on the microbiome is the host’s genetic background. We hypothesized the immune system to be one of the most important genetic factors driving the differences observed between gut microbiomes. Therefore, we are interested in linking the polymorphic molecules that play a role in human immune responses to the composition of the microbiome. HLA molecules are the most polymorphic molecules in our genome and therefore makes an excellent candidate to test such an association/link. To our knowledge for the first time, our results indicate a significant impact of the HLA on the human gut microbiome composition.
Quantitative Analysis of Tissue Secretome Reveals the Diagnostic and Prognostic Value of Carbonic Anhydrase II in Hepatocellular Carcinoma
Authors: Xing Xiaohua , Yuan Hui , Liu Hongzhi , Tan Xionghong , Zhao Bixing , Wang Yingchao , Ouyang Jiahe , Lin Minjie , Huang Aimin , Liu Xiaolong 
Published: January 2020

AbstractEarly detection and intervention are key strategies to reduce mortality, increase long-term survival and improve the therapeutic effects of hepatocellular carcinoma (HCC) patients. Herein, the isobaric tag for relative and absolute quantitation (iTRAQ) quantitative proteomic strategy was used to study the secretome in conditioned media from HCC cancerous tissues, surrounding noncancerous and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC. In total, 22 and 49 secretory proteins were identified to be dysregulated in the cancerous and surrounding noncancerous tissues compared with the distal noncancerous tissues. Among these proteins, carbonic anhydrase II (CA2) was identified to be significantly upregulated in the secretome of cancerous tissues; correspondingly, the serum concentrations of CA2 were remarkably increased in HCC patients than that in normal populations. Interestingly, a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence, and the serum level of CA2 could act as an independent prognostic factor for time to recurrence (TTR) and overall survival (OS). Regarding the mechanism, the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition (EMT) pathway. Taken together, this study identified a novel biomarker for HCC diagnosis and prognosis and provides a valuable resource of the HCC secretome for investigating serological biomarkers.
Temperature controlled high-throughput magnetic tweezers show striking difference in activation energies of replicating viral RNA-dependent RNA polymerases
Authors: Seifert M. , van Nies P. , Papini F.S. , Arnold J.J. , Poranen M.M. , Cameron C.E. , Depken M. , Dulin D. 
Published: January 2020

AbstractRNA virus survival depends on efficient viral genome replication, which is performed by the viral RNA dependent RNA polymerase (RdRp). The recent development of high throughput magnetic tweezers has enabled the simultaneous observation of dozens of viral RdRp elongation traces on kilobases long templates, and this has shown that RdRp nucleotide addition kinetics is stochastically interrupted by rare pauses of 1-1000 s duration, of which the short-lived ones (1-10 s) are the temporal signature of a low fidelity catalytic pathway. We present a simple and precise temperature controlled system for magnetic tweezers to characterize the replication kinetics temperature dependence between 25°C and 45°C of RdRps from three RNA viruses, i.e. the double-stranded RNA bacteriophage Φ6, and the positive-sense single-stranded RNA poliovirus (PV) and human rhinovirus C (HRV-C). We found that Φ6 RdRp is largely temperature insensitive, while PV and HRV-C RdRps replication kinetics are activated by temperature. Furthermore, the activation energies we measured for PV RdRp catalytic state corroborate previous estimations from ensemble pre-steady state kinetic studies, further confirming the catalytic origin of the short pauses and their link to temperature independent RdRp fidelity. This work will enable future temperature controlled study of biomolecular complex at the single molecule level.
Plant-derived Cellulose Scaffolds for Bone Tissue Engineering
Authors: Latour Maxime Leblanc , Tarar Maryam , Hickey Ryan J. , Cuerrier Charles M. , Catelas Isabelle , Pelling Andrew E. 
Published: January 2020

AbstractPlant-derived cellulose biomaterials have recently been utilized in several tissue engineering applications. Naturally-derived cellulose scaffolds have been shown to be highly biocompatiblein vivo, possess structural features of relevance to several tissues, as well as support mammalian cell invasion and proliferation. Recent work utilizing decellularized apple hypanthium tissue has shown that it possesses a pore size and properties similar to trabecular bone. In the present study, we examined the potential of apple-derived cellulose scaffolds for bone tissue engineering (BTE). Confocal microscopy revealed that the scaffolds had a suitable pore size for BTE applications. To analyze theirin vitromineralization potential, MC3T3-E1 pre-osteoblasts were seeded in either bare cellulose scaffolds or in composite scaffolds composed of cellulose and collagen I. Following chemically-induced differentiation, scaffolds were mechanically tested and evaluated for mineralization. The Young’s modulus of both types of scaffolds significantly increased after cell differentiation. Alkaline phosphatase and Alizarin Red staining further highlighted the osteogenic potential of the scaffolds. Histological sectioning of the constructs revealed complete invasion by the cells and mineralization throughout the entire constructs. Finally, scanning electron microscopy demonstrated the presence of mineral aggregates deposited on the scaffolds after differentiation, and energy-dispersive spectroscopy confirmed the presence of phosphate and calcium. In summary, our results indicate that plant-derived cellulose is a promising scaffold candidate for bone tissue engineering applications.
Sources of Off-Target Effects of Vagus Nerve Stimulation Using the Helical Clinical Lead in Domestic Pigs
Authors: Nicolai Evan N. , Settell Megan L. , Knudsen Bruce E. , McConico Andrea L. , Gosink Brian A. , Trevathan James K. , Baumgart Ian W. , Ross Erika K. , Pelot Nicole A. , Grill Warren M. , Gustafson Kenneth J. , Shoffstall Andrew J. , Williams Justin C. , Ludwig Kip A. 
Published: January 2020

AbstractClinical data suggest that efficacious vagus nerve stimulation (VNS) is limited by side effects such as cough and dyspnea that have stimulation thresholds lower than those for therapeutic outcomes. VNS side effects are putatively caused by activation of nearby muscles within the neck, via direct muscle activation or activation of nerve fibers innervating those muscles. Our goal was to determine the thresholds at which various VNS-evoked effects occur in the domestic pig—an animal model with vagus anatomy similar to human—using the bipolar helical lead deployed clinically. Intrafascicular electrodes were placed within the vagus nerve to record electroneurographic (ENG) responses, and needle electrodes were placed in the vagal-innervated neck muscles to record electromyographic (EMG) responses. Contraction of the cricoarytenoid muscle occurred at low amplitudes (∼0.3 mA) and resulted from activation of motor nerve fibers in the cervical vagus trunk within the electrode cuff which bifurcate into the recurrent laryngeal branch of the vagus. At higher amplitudes (∼1.4 mA), contraction of the cricoarytenoid and cricothyroid muscles was generated by current leakage outside the cuff to activate motor nerve fibers running within the nearby superior laryngeal branch of the vagus. Activation of these muscles generated artifacts in the ENG recordings that may be mistaken for compound action potentials representing slowly conducting Aδ-, B-, and C-fibers. Our data resolve conflicting reports of the stimulation amplitudes required for C-fiber activation in large animal studies (>10 mA) and human studies (<250 µA). After removing muscle-generated artifacts, ENG signals with post-stimulus latencies consistent with Aδ- and B-fibers occurred in only a small subset of animals, and these signals had similar thresholds to those that caused bradycardia. By identifying specific neuroanatomical pathways that cause off-target effects and characterizing the stimulation dose-response curves for on- and off-target effects, we hope to guide interpretation and optimization of clinical VNS.
Evaluation of the performance and implications of multinationals: a framework of issues
Authors: Pearce Robert D. , Tang Yuxuan 
Published: January 2020

Purpose
The purpose of this paper is to evaluate multinational enterprises’ (MNEs) performance and impact in contexts beyond their own internal objectives.

Design/methodology/approach
Based on an “eclectic” paradigm and the range of motivations, the framework is designed around three layers of evaluation: “efficiency” as static optimisation, “growth and development” as the dynamics of change on a purely economic view; political/economic sphere in terms of the outcomes of “distribution”, and “sovereignty” on the more purely political concern of how MNEs may undermine countries’ policy independence.

Findings
MNE and national economies have to use current sources of competitiveness efficiently while addressing the necessity to reinforce and refocus them through time. Within these broad agendas, significant interactions and outcomes reflect a range of contingencies conditioned by both MNE objectives and hosts’ competitive status.

Originality/value
The paper concerns economics and MNE role in globalisation. The paper defines a framework of four generic evaluative issues of MNE performance, which subsume a wider range of important but more niche concerns.