bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of combined genomic and transfer analyses to identify factors mediating regional spread of antibiotic resistant bacterial lineages
Authors: Wang Joyce , Foxman Betsy , Pirani Ali , Lapp Zena , Mody Lona , Snitkin Evan 
Published: March 2020

ABSTRACTBackgroundPatients entering nursing facilities (NFs) are frequently colonized with antibiotic resistant organisms (AROs). To understand the determinants of ARO colonization on NF admission we applied whole-genome sequencing to track the spread of four ARO species across regional NFs and evaluated patient-level characteristics and transfer acute-care hospitals (ACHs) as risk factors for colonization.Methods584 patients from six NFs were surveyed for methicillin-resistantStaphylococcus aureus (MRSA), vancomycin-resistantEnterococcus faecalis/faecium(VREfc/VREfm) and ciprofloxacin-resistantEscherichia coli(CipREc) colonization. Genomic analysis was performed to quantify ARO spread between NFs and compared to patient-transfer networks. The association between admission colonization and patient-level variables and recent ACH exposures was examined using multivariable regression models.ResultsThe majority of ARO isolates across study sites belonged to major healthcare-associated lineages: MRSA (ST5;N=89/117); VREfc (ST6;N=68/75); CipREc (ST131; N=58/64), and VREfm (clade A; N=129/129). While the genomic similarity of strains between NF pairs was associated with overlap in their feeder ACHs (Spearman’s rho=0.44-0.75, p<0.05 for MRSA, VREfc and CipREc), limited phylogenetic clustering by either ACH or NF supported regional endemicity. Significant predictors for ARO colonization on NF admission included lower functional status (adjusted odds ratio [aOR]>1 for all four AROs) and recent exposure to glycopeptides (aOR>2 for VREfm, VREfc and MRSA) or 3rd/4th-generation cephalosporins (aOR>2 for MRSA and VREfm). Transfer from specific ACHs was an independent risk factor for only one ARO/ACH pair (VREfm/ACH19, aOR=2.48[1.06-5.83]).ConclusionIn this region, healthcare-associated ARO lineages are endemic among connected NFs and ACHs, making patient characteristics more informative of NF admission colonization risk than exposure to specific ACHs.SummaryUsing a combination of whole-genome sequencing, patient transfer and clinical data, we discerned the dissemination of four high-priority antibiotic-resistant organisms (ARO) in the regional healthcare network, and epidemiolocal drivers underlying the high ARO importation rate into regional nursing facilities.
Reduced arousal during reward anticipation in unmedicated depressed patients
Authors: Schneider Max , Elbau Immanuel G. , Nantawisarakul Taechawidd , Pöhlchen Dorothee , Brückl Tanja ,   BeCOME working group, Czisch Michael , Saemann Philipp G. , Lee Michael D. , Binder Elisabeth B. , Spoormaker Victor I. 
Published: March 2020

AbstractDepression is a debilitating disorder with high prevalence and socioeconomic cost, but the central processes that are altered during depressive states remain largely elusive. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. Using pupillometry and concurrent fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls, we observed reduced pupil dilation during reward anticipation in depressed participants with acute symptomatology. We further observed that individual differences in arousal during reward anticipation track the load and impact of depressive symptoms, a correlation that we replicated in a second sample of unmedicated depressed participants. Moreover, these group differences and correlations were mirrored at the neural level. The upregulation and maintenance of arousal during reward anticipation is a translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification.
Prediction of New Coronavirus Infection Based on a Modified SEIR Model
Authors: Tang Zhou , Li Xianbin , Li Houqiang 
Published: March 2020

BACKGROUNDThe outbreak of the new coronavirus infection in Wuhan City, Hubei Province in December 2019, poses a huge threat to China and even global public health security. Respiratory droplets and contact transmission are the main routes of transmission of new coronaviruses. Compared with SARS and Ebola viruses, new coronavirus infections are infectious during the incubation period. Traditional SEIR (susceptibility-exposure-infection-Removal) There are some differences in conditions for the prediction of the epidemic trend of new coronavirus infection. The outbreak of the new coronavirus infection coincided with the Spring Festival before and after the Chinese Spring Festival.It is necessary to make appropriate optimization and amendments to the traditional model to meet the actual evolution of the epidemic situation.METHODSThe traditional SEIR model assumes that the virus-infected person is not infectious during the incubation period and that the infected person did not take isolation measures during the illness. The transmission of the new coronavirus no longer meets the basic assumptions of the classical kinetic system. Therefore, this article first establishes a modified SEIR model. Predict and analyze the changing trend of the epidemic situation, then estimate the parameters involved in the infection dynamics model, and then use Matlab to simulate the established dynamic equations based on public data and analyze the results. Recommendations for universal prevention and control of infectious diseases.RESULTSThe first case of new coronavirus infection was confirmed in Wuhan on December 8, 2019. When Wuhan City took no action, assuming the average daily number of contacts per infected person k = 5, the number of infected persons will reach about 2,384,803 people; If wuhan adopts the measures of sealing the city on January 22, 2020, under the premise of k=2, the number of infected people decreases by 19,773 compared with that on January 23, and there is no significant change in the time when the number of infected people reaches the peak. Under the premise of k = 1, the number of infected persons was reduced by 14,330 compared with the closure on January 23, and the time to reach the peak of the number of infected persons was reduced by 2 days. If Wuhan City is closed for one day, the number of infected persons will increase from 106,145 to 130,626 under the premise of k = 2; the number of infected persons will increase from 74,369 to 92,010 under the premise of k = 1.CONCLUSIONSComparing the number of confirmed diagnoses actually notified by the department with the number of infected people obtained from the simulation of the model, it can be seen that the city closure measures adopted by the Wuhan Municipal Government on January 23 and the first-level response measures adopted by the country are effective for the epidemic Prevention and control play a vital role. Wearing a mask when going out and avoiding close contact with people can effectively reduce the infection rate.
Chromosomal-level reference genome of the incense treeAquilaria sinensis
Authors: Nong Wenyan , Law Sean T.S. , Wong Annette Y.P. , Baril Tobias , Swale Thomas , Chu Lee Man , Hayward Alexander , Lau David T.W. , Hui Jerome H.L. 
Published: March 2020

AbstractTrees in the genusAquilaria(Thymelaeaceae) are known as lign aloes, and are native to the forests of southeast Asia. Lign aloes produce agarwood as an antimicrobial defence. Agarwood has a long history of cultural and medicinal use, and is of considerable commercial value. However, due to habitat destruction and over collection, lign aloes are threatened in the wild. We present a chromosomal-level assembly forAquilaria sinensis, a lign aloe endemic to China known as the incense tree, based on Illumina short-read, 10X Genomics linked-read, and Hi-C sequencing data. Our 783.8MbpA. sinensisgenome assembly is of high physical contiguity, with a scaffold N50 of 87.6Mbp, and high completeness, with a 95.8% BUSCO score for eudicotyledon genes. We include 17 transcriptomes from various plant tissues, providing a total of 35,965 gene models. We reveal the first complete set of genes involved in sesquiterpenoid production, plant defence, and agarwood production for the genusAquilaria, including genes involved in the biosynthesis of sesquiterpenoids via the mevalonic acid (MVA), 1-deoxy-D-xylulose-5-phosphate (DXP), and methylerythritol phosphate (MEP) pathways. We perform a detailed repeat content analysis, revealing that transposable elements account for ∼61% of the genome, with major contributions fromgypsy-like andcopia-like LTR retroelements. We also provide a comparative analysis of repeat content across sequenced species in the order Malvales. Our study reveals the first chromosomal-level genome assembly for a tree in the genusAquilariaand provides an unprecedented opportunity to address a variety of applied, genomic and evolutionary questions in the Thymelaeaceae more widely.
Trends in animal model preference for preclinical drug testing for type-2 diabetes and future directions
Authors: Franco Nuno Henrique , Miranda Sónia Batista , Kovacs Nora , Nagy Attila , Akinsolu Folahanmi Tomiwa , Olsson I Anna S , Varga Orsolya 
Published: March 2020

AbstractThe importance of selecting accurate animal models of disease has become increasingly salient in recent years. This is particularly important for preclinical tests carried out to predict drug efficacy and safety for humans. We mapped past and current trends in animal model selection for type-2 Diabetes Mellitus (T2DM) antidiabetic drug research, and evaluate results in light of their implications for translational research.From data gathered from published studies on 41 orally administered antidiabetic drug classes from the ‘MEDLINE Evaluator’ web service, we found animal model choice trends within – and across – drug classes to be substantially similar, with outbred rat strains being more prevalently used, since the 1990s. The observed consistency in choice of animal models in T2DM is advantageous for replicability and comparability of experiments, but prevalence of outbred strains raises a few concerns.In face of current criticism of the translational value of animal tests, predictive validity must be assessed on a case-by-case basis. We address some of the issues pertaining the most popular animal models in antidiabetic drug development and testing, including the lack of information on their predictive validity, and propose a ‘back translation’ approach to estimate it retrospectively.
Ranking Cancer Drivers via Betweenness-based Outlier Detection and Random Walks
Authors: Erten Cesim , Houdjedj Aissa , Kazan Hilal 
Published: March 2020

AbstractBackgroundRecent cancer genomic studies have generated detailed molecular data on a large number of cancer patients. A key remaining problem in cancer genomics is the identification of driver genes. Results: We propose BetweenNet, a computational approach that integrates genomic data with a protein-protein interaction network to identify cancer driver genes. BetweenNet utilizes a measure based on betweenness centrality on patient specific networks to identify the so-calledoutlier genesthat correspond to dysregulated genes for each patient. Setting up the relationship between the mutated genes and the outliers through a bipartite graph, it employs a random-walk process on the graph, which provides the final prioritization of the mutated genes. We compare BetweenNet against state-of-the art cancer gene prioritization methods on lung, breast, and pan-cancer datasets. Conclusions: Our evaluations show that BetweenNet is better at recovering known cancer genes based on multiple reference databases. Additionally, we show that the GO terms and the reference pathways enriched in BetweenNet ranked genes and those that are enriched in known cancer genes overlap significantly when compared to the overlaps achieved by the rankings of the alternative methods.
Strategies for identifying dynamic regions in protein complexes: flexibility changes accompany methylation in chemotaxis receptor signaling states
Authors: Malik Nikita , Wahlbeck Katherine A , Thompson Lynmarie K 
Published: March 2020

AbstractBacterial chemoreceptors are organized in arrays composed of helical receptors arranged as trimers of dimers, coupled to a histidine kinase CheA and a coupling protein CheW. Ligand binding to the external domain inhibits the kinase activity, leading to a change in the swimming behavior. Adaptation to an ongoing stimulus involves reversible methylation and demethylation of specific glutamate residues. However, the exact mechanism of signal propagation through the helical receptor to the histidine kinase remains elusive. Dynamics of the receptor cytoplasmic domain is thought to play an important role in the signal transduction, and current models propose inverse dynamic changes in different regions of the receptor. We hypothesize that the adaptational modification (methylation) controls the dynamics by stabilizing a partially ordered domain, which in turn modulates the binding of the kinase, CheA. We investigated the difference in dynamics between the methylated and unmethylated states of the chemoreceptor using solid-state NMR. The unmethylated receptor (CF4E) shows increased flexibility relative to the methylation mimic (CF4Q). Methylation helix 1 (MH1) has been shown to be flexible in the methylated receptor. Our analysis indicates that in addition to MH1, methylation helix 2 also becomes flexible in the unmethylated receptor. In addition, we have demonstrated that both states of the receptor have a rigid region and segments with intermediate dynamics. The strategies used in the study for identifying dynamic regions are applicable to a broad class of proteins and protein complexes with intrinsic disorder and dynamics spanning multiple timescales.Graphical AbstractHighlightsReceptors exhibit greater ns timescale dynamics in unmethylated vs methylated stateMethylation helix 2 likely involved in increased flexibility of unmethylated stateDynamics occur on multiple timescales in both states of the receptor
Calcium-induced calcium release and type 3 ryanodine receptors modulate the slow afterhyperpolarising current, sIAHP, and its potentiation in hippocampal pyramidal neurons
Authors: Tedoldi Angelo , Ludwig Petra , Fulgenzi Gianluca , Takeshima Hiroshi , Pedarzani Paola , Stocker Martin 
Published: March 2020

AbstractThe slow afterhyperpolarising current, sIAHP, is a Ca2+-dependent current that plays an important role in the late phase of spike frequency adaptation. sIAHPis activated by voltage-gated Ca2+channels, while the contribution of calcium from ryanodine-sensitive intracellular stores, released by calcium-induced calcium release (CICR), is controversial in hippocampal pyramidal neurons. Three types of ryanodine receptors (RyR1-3) are expressed in the hippocampus, with RyR3 showing a predominant expression in CA1 neurons. We investigated the specific role of CICR, and particularly of its RyR3-mediated component, in the regulation of the sIAHPamplitude and time course, and the activity-dependent potentiation of the sIAHPin rat and mouse CA1 pyramidal neurons.Here we report that enhancement of CICR by caffeine led to an increase in sIAHPamplitude, while inhibition of CICR by ryanodine caused a small, but significant reduction of sIAHP. Inhibition of ryanodine-sensitive Ca2+stores by ryanodine or depletion by the SERCA pump inhibitor cyclopiazonic acid caused a substantial attenuation in the sIAHPactivity-dependent potentiation in both rat and mouse CA1 pyramidal neurons. Neurons from mice lacking RyR3 receptors exhibited a sIAHPwith features undistinguishable from wild-type neurons, which was similarly reduced by ryanodine. However, the lack of RyR3 receptors led to a faster and reduced activity-dependent potentiation of sIAHP.We conclude that ryanodine receptor-mediated CICR contributes both to the amplitude of the sIAHPat steady state and its activity-dependent potentiation in rat and mouse hippocampal pyramidal neurons. In particular, we show that RyR3 receptors play an essential and specific role in shaping the activity-dependent potentiation of the sIAHP. The modulation of activity-dependent potentiation of sIAHPby RyR3-mediated CICR contributes to plasticity of intrinsic neuronal excitability and is likely to play a critical role in higher cognitive functions, such as learning and memory.
Consistent behavioral syndrome across seasons in an invasive freshwater fish
Authors: Lukas Juliane , Kalinkat Gregor , Miesen Friedrich Wilhelm , Landgraf Tim , Krause Jens , Bierbach David 
Published: March 2020

AbstractUnderstanding the linkage between behavioral types and dispersal tendency has become a pressing issue in light of global change and biological invasions. Here, we explore whether dispersing individuals exhibit behavioral types that differ from those remaining in the source population. We investigated a feral population of guppies (Poecilia reticulata) that undergoes a yearly range shift cycle. Guppies are among the most widespread invasive species in the world, but in temperate regions these tropical fish can only survive in winter-warm freshwaters. Established in a thermally-altered stream in Germany, guppies are confined to a warm-water influx in winter, but can spread to peripheral parts as these become thermally accessible. We sampled fish from the source population and a winter-abandoned site in March, June and August. Fish were tested for boldness, sociability and activity involving open-field tests including interactions with a robotic social partner. Guppies differed consistently among each other in all three traits. Behavioral trait expression in the source population differed across seasons, however, we could not detect differences between source and downstream populations. Instead, all sampled populations exhibited a remarkably stable behavioral syndrome between boldness and activity despite strong seasonal changes in water temperature and associated environmental factors. We conclude that random drift (opposed to personality-biased dispersal) is a more likely dispersal mode for guppies, at least in the investigated stream. In the face of fluctuating environments, guppies seem to be extremely effective in keeping behavioral expressions constant, which could help explain their successful invasion and adaptation to disturbed habitats.
A metabolic shift to glycolysis promotes zebrafish tail regeneration through TGF–β dependent dedifferentiation of notochord cells to form the blastema
Authors: Sinclair Jason W. , Hoying David R. , Bresciani Erica , Nogare Damian Dalle , Needle Carli D. , Wu Weiwei , Bishop Kevin , Elkahloun Abdel G. , Chitnis Ajay , Liu Paul , Burgess Shawn M. 
Published: March 2020

AbstractMammals are generally poor at tissue regeneration, in contrast, fish maintain a high capacity for regenerating complex tissues after injury. Using larval zebrafish, we show that tail amputation triggers an metabolic shift to glycolysis in cells surrounding the notochord as they reposition to the amputation site. Blocking glycolysis prevents the fin from regenerating after amputation due to the failure to form a normal, pluripotent blastema. We performed a time series of scRNA-sequencing on regenerating tails under normal conditions or in the absence of glycolysis. Strikingly, we detected a transient cell population in the single cell analysis that represents notochord sheath cells undergoing a TGF–β dependent dedifferentiation and epithelium-to-mesenchyme transition to become pluripotent blastema cells. We further demonstrated that the metabolic switch to glycolysis is required for TGF–β signaling and blocking either glycolysis or TGF–β receptors results in aberrant blastema formation through the suppression of essential EMT mediators such assnai1.
Electroactive biofilms on surface functionalized anodes: the anode respiring behavior of a novel electroactive bacterium,Desulfuromonas acetexigens
Authors: Katuri Krishna P. , Kamireddy Sirisha , Kavanagh Paul , Mohammad Ali , Conghaile Peter Ó , Kumar Amit , Saikaly Pascal E. , Leech Dónal 
Published: March 2020

AbstractSurface chemistry is known to influence the formation, composition and electroactivity of electron-conducting biofilms with however limited information on the variation of microbial composition and electrochemical response during biofilm development to date. Here we present voltammetric, microscopic and microbial community analysis of biofilms formed under fixed applied potential for modified graphite electrodes during early (90 h) and mature (340 h) growth phases. Electrodes modified to introduce hydrophilic groups (−NH2, −COOH and −OH) enhance early-stage biofilm formation compared to unmodified or electrodes modified with hydrophobic groups (−C2H5). In addition, early-stage films formed on hydrophilic electrodes were dominated by the gram-negative sulfur-reducing bacteriumDesulfuromonas acetexigenswhileGeobactersp. dominated on −C2H5and unmodified electrodes. As biofilms mature, current generation becomes similar, andD. acetexigensdominates in all biofilms irrespective of surface chemistry. Electrochemistry of pure cultureD. acetexigensbiofilms reveal that this microbe is capable of forming electroactive biofilms producing considerable current density of > 9 A/m2in a short period of potential induced growth (~19 h followed by inoculation) using acetate as an electron donor. The inability ofD. acetexigensbiofilms to use H2as a sole source electron donor for current generation shows promise for maximizing H2recovery in single-chambered microbial electrolysis cell systems treating wastewaters.HighlightsAnode surface chemistry affects the early stage biofilm formation.Hydrophilic anode surfaces promote rapid start-up of current generation.Certain functionalized anode surfaces enriched theDesulfuromonas acetexigens.D. acetexigensis a novel electroactive bacteria.D. acetexigensbiofilms can produce high current density in a short period of potential induced growthD. acetexigenshas the ability to maximize the H2recovery in MEC.Abstract FigureTOC – Graphical abstract