bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza-associated mortality for circulatory and respiratory causes during the 2013-2014 through the 2018-2019 influenza seasons in Russia
Authors: Goldstein Edward 
Published: November 2019

AbstractBackgroundInformation on influenza-associated mortality in Russia is limited and largely related to deaths with influenza in the diagnosis that represent a small fraction of all influenza-associated deaths.MethodsUsing previously developed methodology (Goldstein et al., Epidemiology 2012), we regressed the monthly rates of mortality for respiratory causes, as well as circulatory causes (available from the Russian Federal State Statistics Service (Rosstat)) during the 2013/14 through the 2018/19 influenza seasons linearly against the monthly proxies for the incidence of influenza A/H3N2, A/H1N1 and B (obtained using data from the Smorodintsev Research Institute of Influenza (RII) on influenza/ARI consultations, testing of respiratory specimens and genetic/antigenic characterization of influenza viruses), adjusting for the baseline rates of mortality not associated with influenza circulation and temporal trends.ResultsFor the 2013/14 through the 2018/19 seasons, influenza circulation was associated with an average annual 17636 (95% CI (9482,25790)) deaths for circulatory causes and 4179 (3250,5109) deaths for respiratory causes, with the largest number of deaths (32298 (18071,46525) for circulatory causes and 6689 (5019,8359) for respiratory causes) estimated during the 2014/15 influenza season. Influenza A/H3N2 was responsible for 51.8% of all circulatory influenza-associated deaths and 37.2% of all respiratory influenza-associated deaths. Influenza A/H1N1 was responsible for 23.4% of all circulatory influenza-associated deaths and 29.5% of all respiratory influenza-associated deaths. Influenza B was responsible for 24.9% of all circulatory influenza-associated deaths and 33.3% of all respiratory influenza-associated deaths, with the overwhelming majority of those deaths being caused by the B/Yamagata viruses. Compared to the 2013/14 through the 2015/16 seasons, during the 2016/17 through the 2018/19 seasons (when levels of influenza vaccination were significantly higher), the volume of influenza-associated mortality declined by about 16.1%, or 3809 annual respiratory and circulatory deaths.ConclusionsInfluenza circulation is associated with a substantial mortality burden in Russia, particularly for circulatory deaths, with some reduction in mortality rates observed following the major increase in influenza vaccination coverage. Those results support the potential utility of further extending the levels of influenza vaccination, the use of quadrivalent influenza vaccines, and extra efforts for protecting individuals with circulatory disease in Russia, including vaccination and the use of antiviral medications.
Attention-related modulation of caudate neurons depends on superior colliculus activity
Authors: Herman James P. , Arcizet Fabrice , Krauzlis Richard J. 
Published: November 2019

AbstractRecent work has implicated the basal ganglia in visual perception and attention, in addition to their traditional role in motor control. The basal ganglia, especially the caudate nucleus “head” (CDh) of the striatum, receive indirect anatomical connections from the superior colliculus, a midbrain structure that is known to play a crucial role in the control of visual attention. To test the possible functional relationship between these subcortical structures, we recorded CDh neuronal activity before and during unilateral SC inactivation in a spatial attention task. SC inactivation significantly altered the attention-related modulation of CDh neurons and strongly impaired the classification of task epochs based on CDh activity. Only inactivation of the same-side of SC as recorded CDh neurons, not the opposite-side, had these effects. These results demonstrate a novel interaction between SC activity and attention-related visual processing in the basal ganglia.
Histone deacetylase 9 promoter hypomethylation associated with adipocyte dysfunction is a statin-related metabolic effect
Authors: Khamis Amna , Boutry Raphael , Canouil Mickaël , Mathew Sumi , Lobbens Stephane , Crouch Hutokshi , Andrew Toby , Abderrahmani Amar , Tamanini Filippo , Froguel Philippe 
Published: November 2019

AbstractBackgroundAdipogenesis, the process whereby preadipocytes differentiate into mature adipocytes, is crucial for maintaining metabolic homeostasis. Cholesterol lowering statins increase type 2 diabetes (T2D) risk possibly by affecting adipogenesis and insulin resistance but the (epi)genetic mechanisms involved are unknown. Here, we characterised the effects of statin treatment on adipocyte differentiation using in vitro human preadipocytes cell model to identify putative effective genes.ResultsStatin treatment during adipocyte differentiation caused a reduction in key genes involved in adipogenesis, such as ADIPOQ, GLUT4 and ABCG1. Using Illumina’s Infinium ‘850K’ Methylation EPIC array, we found a significant hypomethylation of cg14566882, located in the promoter of the histone deacetylase 9 (HDAC9) gene, in response to two types of statins (atorvastatin and mevastatin), which correlates with an increased HDAC9 mRNA expression. HDAC9 is a transcriptional repressor of the cholesterol efflux ABCG1 gene expression, which is epigenetically modified in obesity and prediabetic states. Thus, we assessed the putative impact of ABCG1 knockdown in mimicking the effect of statin in adipogenesis. ABCG1 KD reduced the expression of key genes involved in adipocyte differentiation and decreased insulin signalling and glucose uptake. In human blood cells from two cohorts, ABCG1 expression was impaired in response to statins, confirming that ABCG1 is in vivo targeted by these drugs.ConclusionsWe identified an epigenetic link between adipogenesis and adipose tissue insulin resistance in the context of T2D risk associated with statin use, which has important implications as HDAC9 and ABCG1 are considered potential therapeutic targets for obesity and metabolic diseases.
NorK, a novel norfloxacin efflux pump in Staphylococcus aureus
Authors: Briaud Paul , Baude Jessica , Bastien Sylvère , Camus Laura , Vandenesch François , Moreau Karen 
Published: November 2019

AbstractA novel efflux pump similar to Nor efflux pumps and designated as NorK was identified in Staphylococcus aureus. It contributes to norfloxacin resistance and presents a high level of expression in different strains. Its expression is not regulated by MgrA, unlike other genes of the nor gene family, suggesting that NorK could be important in the absence of expression of other nor genes.
Phase variation-based biosensors for bacteriophage detection and phage receptor discrimination
Authors: Olivenza David R. , Casadesús Josep , Ansaldi Mireille 
Published: November 2019

AbstractEnvironmental monitoring of bacteria using phage-based biosensors has been widely developed for many different species. However, there are only a few available methods to detect specific bacteriophages in raw environmental samples. In this work, we developed a simple and efficient assay to rapidly monitor the phage content of a given sample. The assay is based on the bistable expression of theSalmonella enterica opvABoperon. Under regular growth conditions,opvABis only expressed by a small fraction of the bacterial subpopulation. In the OpvABONsubpopulation, synthesis of the OpvA and OpvB products shortens the O-antigen in the lipopolysaccharide and confers resistance to phages that use LPS as a receptor. As a consequence, the OpvABONsubpopulation is selected in the presence of such phages. Using anopvAB::gfpfusion, we could monitor LPS-binding phages in various media, including raw water samples. To enlarge our phage-biosensor panoply, we also developed several coliphage biosensors that proved efficient to detect LPS- as well as protein-binding coliphages. Moreover, the combination of these tools allows to identify what is the bacterial receptor triggering phage infection. TheopvAB::gfpbiosensor thus comes in different flavours to efficiently detect a wide range of bacteriophages and identify the type of receptor they recognize.ImportanceDetection and accurate counting of bacteriophages, the viruses that specifically infect bacteria, from environmental samples still constitutes a challenge for those interested in isolating and characterizing bacteriophages for ecological or biotechnological purposes. This work provides a simple and accurate method based on the bi-stable expression of genes that confer resistance to certain classes of bacteriophages in different bacterial models. It paves the way for future development of highly efficient phage biosensors that can discriminate among several receptor-binding phages and that could be declined in many more versions. In a context where phage ecology, research, and therapy are flourishing again, it becomes essential to possess simple and efficient tools for phage detection.
Mildew Locus O facilitates colonization by arbuscular mycorrhiza in angiosperms
Authors: Jacott Catherine N. , Charpentier Myriam , Murray Jeremy D. , Ridout Christopher J. 
Published: November 2019

SummaryLoss of barley Mildew Resistance Locus O (MLO) is known to confer durable and robust resistance to powdery mildew (Blumeria graminis), a biotrophic fungal leaf pathogen. Based on the increased expression of MLO in mycorrhizal roots and its presence in a clade of the MLO family that is specific to mycorrhizal-host species, we investigated the potential role of MLO in arbuscular mycorrhizal interactions.Using mutants from barley, wheat, and Medicago truncatula, we demonstrate a role for MLO in colonization by the arbuscular mycorrhizal fungi Rhizophagus irregularis.Early mycorrhizal colonization was reduced in mlo mutants of barley, wheat and Medicago truncatula, and this was accompanied by a pronounced decrease in the expression of many of the key genes required for intracellular accommodation of arbuscular mycorrhizal fungi.These findings suggest that the primary role of MLO in angiosperms is in the establishment of symbiotic associations with beneficial fungi, which has been appropriated by powdery mildew.
The neural computation of human prosocial choices in complex motivational states
Authors: Saulin Anne , Horn Ulrike , Lotze Martin , Kaiser Jochen , Hein Grit 
Published: November 2019

AbstractMotives motivate human behavior. Most behaviors are driven by more than one motive, yet it is unclear how different motives interact and how such motive combinations affect the neural computation of the behaviors they drive. To answer this question, we induced two prosocial motives simultaneously (multi-motive condition) and separately (single motive conditions). After the different motive inductions, participants performed the same choice task in which they allocated points in favor of the other person (prosocial choice) or in favor of themselves (egoistic choice). We used fMRI to assess prosocial choice-related brain responses and drift diffusion modelling to specify how motive combinations affect individual components of the choice process. Our results showed that the combination of the two motives in the multi-motive condition increased participants’ choice biases prior to the behavior itself. On the neural level, these changes in initial prosocial bias were associated with neural responses in the bilateral dorsal striatum. In contrast, the efficiency of the prosocial decision process was comparable between the multi-motive and the single-motive conditions. These findings provide insights into the computation of prosocial choices in complex motivational states, the motivational setting that drives most human behaviors.HighlightsActivating different social motives simultaneously can enhance prosocial choicesMulti-motive combinations change initial prosocial biasesDorso-striatal activation increases with larger increase of prosocial biasMulti-motive combinations modulate relative response caution
The effect of experimental lead pollution on DNA methylation in a wild bird population
Authors: Mäkinen Hannu , van Oers Kees , Eeva Tapio , Laine Veronika N. , Ruuskanen Suvi 
Published: November 2019

AbstractAnthropogenic pollution is known to negatively influence an organism’s physiology, behavior and fitness. Epigenetic regulation, such as DNA methylation, has been hypothesized as one mechanism to mediate such effects, yet studies in wild species are lacking. We first investigated the effects of early-life exposure to the heavy metal lead (Pb) on DNA methylation levels in a wild population of great tits (Parus major), by experimentally exposing nestlings to lead at environmentally relevant levels. Secondly, we studied the effects of heavy metal exposure in a population close to a copper smelter, where birds suffer from pollution-related decrease in food quality. For both comparisons, the analysis of about million CpGs covering most of the annotated genes, revealed that regions enriched for developmental processes showed pollution-related changes in DNA methylation, but the results were not consistent with binomial and beta binomial regression. Our study indicates that post-natal anthropogenic heavy metal exposure can affect methylation levels of development related genes in a wild bird population.
Antimicrobial solid media for screening non-sterile Arabidopsis thaliana seeds
Authors: Behrendorff James B. Y. H. , Borràs-Gas Guillem , Pribil Mathias 
Published: November 2019

AbstractBackgroundStable genetic transformation of plants is a low-efficiency process, and identification of positive transformants usually relies on screening for expression of a co-transformed marker gene. Often this involves germinating seeds on solid media containing a selection reagent. Germination on solid media requires surface sterilization of seeds and careful aseptic technique to prevent microbial contamination, but surface sterilization techniques are time consuming and can cause seed mortality if not performed carefully. We developed an antimicrobial cocktail that can be added to solid media to inhibit bacterial and fungal growth without impairing germination, allowing us to bypass the surface sterilization step.ResultsAdding a combination of terbinafine (1 µM) and timentin (200 mg/L) to solid media delayed the onset of observable microbial growth and did not affect germination of non-sterile seeds from ten different wild-type and mutant Arabidopsis thaliana accessions. The method was also compatible with Nicotiana tabacum germination. Seedlings sown in non-sterile conditions could be maintained on antimicrobial media for up to a week without observable contamination. The antimicrobial cocktail was compatible with rapid screening methods for hygromycin B, phosphinothricin (BASTA) and nourseothricin resistance genes, meaning that positive transformants can be identified from non-sterile seeds in as little as four days after stratification and transferred to soil before the onset of visible microbial contamination.ConclusionThe antimicrobial cocktail presented here delays microbial growth for long enough to permit germination of non-sterile Arabidopsis thaliana seedlings on solid media and it is compatible with rapid screening methods. We were able to select genetic transformants on solid media without seed surface sterilization, eliminating a tedious and time-consuming step.
A novel pH-regulated, unusual 603 bp overlapping protein coding gene pop is encoded antisense to ompA in Escherichia coli O157:H7 (EHEC)
Authors: Zehentner Barbara , Ardern Zachary , Kreitmeier Michaela , Scherer Siegfried , Neuhaus Klaus 
Published: November 2019

AbstractAntisense transcription is well known in bacteria. However, translation of antisense RNAs is typically not considered, as the implied overlapping coding at a DNA locus is assumed to be highly improbable. Therefore, such overlapping genes are systematically excluded in prokaryotic genome annotation. Here we report an exceptional 603 bp long open reading frame completely embedded in antisense to the gene of the outer membrane protein ompA. Ribosomal profiling revealed translation of the mRNA and the protein was detected in Western blots. A σ70 promoter, transcription start site, Shine-Dalgarno motif and rho-independent terminator were experimentally validated. A pH-dependent phenotype conferred by the protein was shown in competitive overexpression growth experiments of a translationally arrested mutant versus wild type. We designate this novel gene pop (pH-regulated overlapping protein-coding gene). Increasing evidence based on ribosome-profiling indicates translation of antisense RNA, suggesting that more overlapping genes of unknown function may exist in bacteria.
Hormonal control of motivational circuitry orchestrates the transition to sexuality in Drosophila
Authors: Zhang Stephen X. , Glantz Ethan H. , Rogulja Dragana , Crickmore Michael A. 
Published: November 2019

SUMMARYNewborns and hatchlings of many species perform incredibly sophisticated behaviors, but all vertebrates and many invertebrates selectively abstain from sexual activity at the beginning of life. Hormonal changes have long been associated with adolescence, but it is not clear how these circulating factors create a new motivation and drive its associated behaviors. We show that the transition to sexuality in maleDrosophilais controlled by juvenile hormone, which spikes at eclosion and declines over days as the propensity for courtship gradually increases. Juvenile hormone directly inhibits the activity of at least three courtship-motivating circuit elements, ensuring the complete suppression of sexual motivation and behavior. Blocking or overriding these inhibitory mechanisms evokes immediate and robust sexual behavior from very young and otherwise asexual males. These results provide a first example of hormonal changes gating the transition to sexuality by activating latent, but largely developed and functional, motivational circuitry.
Model-based inference of punctuated molecular evolution
Authors: Manceau Marc , Marin Julie , Morlon Hélène , Lambert Amaury 
Published: November 2019

AbstractIn standard models of molecular evolution, DNA sequences evolve through asynchronous substitutions according to Poisson processes with a constant rate (called the molecular clock) or a time-varying rate (relaxed clock). However, DNA sequences can also undergo episodes of fast divergence that will appear as synchronous substitutions affecting several sites simultaneously at the macroevolutionary time scale. Here, we develop a model combining basal, clock-like molecular evolution with episodes of fast divergence called spikes arising at speciation events. Given a multiple sequence alignment and its time-calibrated species phylogeny, our model is able to detect speciation events (including hidden ones) co-occurring with spike events and to estimate the probability and amplitude of these spikes on the phylogeny. We identify the conditions under which spikes can be distinguished from the natural variance of the clock-like component of molecular evolution and from temporal variations of the clock. We apply the method to genes underlying snake venom proteins and identify several spikes at gene-specific locations in the phylogeny. This work should pave the way for analyses relying on whole genomes to inform on modes of species diversification.
Intra-Species Differences in Population Size shape Life History and Genome Evolution
Authors: Willemsen David , Cui Rongfeng , Reichard Martin , Valenzano Dario Riccardo 
Published: November 2019

AbstractThe evolutionary forces shaping life history trait divergence within species are largely unknown. Killifish (oviparous Cyprinodontiformes) evolved an annual life cycle as an exceptional adaptation to life in arid savannah environments characterized by seasonal water availability. The turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate known to science and displays differences in lifespan among wild populations, representing an ideal natural experiment in the evolution and diversification of life history. Here, by combining genome sequencing and population genetics, we investigate the evolutionary forces shaping lifespan among turquoise killifish populations. We generate an improved reference assembly for the turquoise killifish genome, trace the evolutionary origin of the sex chromosome, and identify genes under strong positive and purifying selection, as well as those evolving neutrally. We find that the shortest-lived turquoise killifish populations, which dwell in fragmented and isolated habitats at the outer margin of the geographical range of the species, are characterized by small effective population size and accumulate throughout the genome several small to large-effect deleterious mutations due to genetic drift. The genes most affected by drift in the shortest-lived turquoise killifish populations are involved in the WNT signalling pathway, neurodegenerative disorders, cancer and the mTOR pathway. As the populations under stronger genetic drift are the shortest-lived ones, we propose that limited population size due to habitat fragmentation and repeated population bottlenecks, by causing the genome-wide accumulation of deleterious mutations, cumulatively contribute to the short adult lifespan in turquoise killifish populations.
Energy Expenditure during Cell Spreading Regulates the Stem Cells Responses to Matrix Stiffness
Authors: Xie Jing , Bao Min , Hu Xinyu , Koopman Werner J. H. , Huck Wilhelm T. S. 
Published: November 2019

AbstractCells respond to the mechanical properties of the extracellular matrix (ECM) through formation of focal adhesions (FAs), re-organization of the actin cytoskeleton and adjustment of cell contractility. These are energy-demanding processes, but a potential causality between mechanical cues (matrix stiffness) and cellular (energy) metabolism remains largely unexplored. Here, we culture human mesenchymal stem cells (hMSCs) on stiff (20 kPa) or soft (1 kPa) substrate and demonstrate that cytoskeletal reorganization and FA formation spreading on stiff substrates lead to a drop in intracellular ATP levels, correlates with the activation of AMP-activated protein kinase (AMPK). The resulting increase in ATP levels further facilitates cell spreading and reinforces cell tension of the steady state, and coincides with nuclear localization of YAP/TAZ and Runx2. While on soft substrates (1 kPa), lowered ATP levels limit these cellular mechanoresponses. Furthermore, genetic ablation of AMPK lowered cellular ATP levels on stiff substrate and strongly reduced responses to substrate stiffness. Together, these findings reveal a hitherto unidentified relationship between energy expenditure and the cellular mechanoresponse, and point to AMPK as a key mediator of stem cell fate in response to ECM mechanics.