bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolically-Driven Maturation of hiPSC-Cell Derived Cardiac Chip
Authors: Huebsch Nathaniel , Charrez Berenice , Siemons Brian , Boggess Steven C. , Wall Samuel , Neiman Gabriel , Charwat Verena , Jæger Karoline H. , Cleres David , Telle Åshild , Lee-Montiel Felipe T. , Jeffreys Nicholas C. , Deveshwar Nikhil , Edwards Andrew , Serrano Jonathan , Snuderl Matija , Stahl Andreas , Tveito Aslak , Miller Evan W. , Healy Kevin E. 
Published: December 2018

AbstractHuman induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) are a promising in vitro tool for drug development and disease modeling, but their immature electrophysiology limits diagnostic utility. Tissue engineering approaches involving aligned 3D cultures enhance hiPSC-CM structural maturation but are insufficient to induce mature electrophysiology. We hypothesized that mimicking post-natal switching of the heart’s primary ATP source from glycolysis to fatty acid oxidation could enhance electrophysiological maturation of hiPSC-CM. We combined hiPSC-CM with microfabricated culture chambers to form 3D cardiac microphysiological systems (MPS) that enhanced immediate microtissue alignment and tissue specific extracellular matrix (ECM) production. Using Robust Experimental design, we identified a maturation media that improved calcium handling in MPS derived from two genetically distinct hiPSC sources. Although calcium handling and metabolic maturation were improved in both genotypes, there was a divergent effect on action potential duration (APD): MPS that started with abnormally prolonged APD exhibited shorter APD in response to maturation media, whereas the same media prolonged the APD in MPS that started with aberrantly short APD. Importantly, the APD of both genotypes was brought near the range of 270-300ms observed in human left ventricular cardiomyocytes. Mathematical modeling explained these divergent phenotypes, and further predicted the response of matured MPS to drugs with known pro-arrhythmic effects. These results suggest that systematic combination of biophysical stimuli and metabolic cues can enhance the electrophysiological maturation of hiPSC-derived cardiomyocytes. However, they also reveal that maturation-inducing cues can have differential effects on electrophysiology depending on the baseline phenotype of hiPSC-CM. In silico models provide a valuable tool for predicting how changes in cellular maturation will manifest in drug responsiveness.
In vivo microscopy reveals the impact ofPseudomonas aeruginosasocial interactions on host colonization
Authors: Rezzoagli Chiara , Granato Elisa T. , Kümmerli Rolf 
Published: December 2018

AbstractPathogenic bacteria engage in social interactions to colonize hosts, which include quorum-sensing-mediated communication and the secretion of virulence factors that can be shared as “public goods” between individuals. While in-vitro studies demonstrated that cooperative individuals can be displaced by “cheating” mutants freeriding on social acts, we know little about social interactions in infections. Here, we developed a live imaging system to track virulence factor expression and social strain interactions in the human pathogenPseudomonas aeruginosacolonizing the gut ofCaenorhabditis elegans. We found that shareable siderophores and quorum-sensing systems are expressed during infections, affect host gut colonization, and benefit nonproducers. However, non-producers were unable to cheat and outcompete producers, probably due to the spatial segregation of strains within the gut. Our results shed new light on bacterial social interactions in infections and reveal potential limits of therapeutic approaches that aim to capitalize on social dynamics between strains for infection control.
Polarized light information modulates sensorimotor decision making in goldfish
Authors: Otero Coronel Santiago , Berón de Astrada Martín , Medan Violeta 
Published: December 2018

AbstractAnimal survival relays on environmental information gathered by their sensory systems. In invertebrates the polarization angle of light is known to provide vital information for a wide range of visual tasks. However, the role of polarization sensitivity in vertebrates remains poorly understood. Here we study if polarization vision enhances threat detection in goldfish. We found that adding a polarization cue to a low intensity contrast looming stimulus biases the type of evasive behavior the animals perform. While low contrast looms mostly evoke subtle alarm reactions, the addition of a polarized cue dramatically increases the probability of eliciting a fast escape maneuver, the C-start response. Goldfish can be startled by polarized light stimuli coming not only from above but also from the sides indicating that polarization sensitivity spans large areas of the retina. In addition, we observed that while low intensity contrast looms preferentially elicit alarm behaviours, high intensity contrast looms rarely induced them, but elicited C-start responses with a high probability. Together, our results show that the addition of a polarized light cue to a low intensity contrast stimulus shifts animal’s decision making from low threshold alarm responses to the higher threshold C-start escape behaviour. This additional visual cue, thus, might aid underwater threat detection and predator avoidance in the animal’s natural environment.Summary statementThis study gives the first compelling evidence that fish can use polarized light information to improve their decision making in the context of visual threat detection.
Hearing impairment is associated with enhanced neural tracking of the speech envelope
Authors: Decruy Lien , Vanthornhout Jonas , Francart Tom 
Published: December 2018

AbstractElevated hearing thresholds in hearing impaired adults are usually compensated by providing amplification through a hearing aid. In spite of restoring hearing sensitivity, difficulties with understanding speech in noisy environments often remain. One main reason is that sensorineural hearing loss not only causes loss of audibility but also other deficits, including peripheral distortion but also central temporal processing deficits. To investigate the neural consequences of hearing impairment in the brain underlying speech-in-noise difficulties, we compared EEG responses to natural speech of 14 hearing impaired adults with those of 14 age-matched normal-hearing adults. We measured neural envelope tracking to sentences and a story masked by different levels of a stationary noise or competing talker. Despite their sensorineural hearing loss, hearing impaired adults showed higher neural envelope tracking of the target than the competing talker, similar to their normal-hearing peers. Furthermore, hearing impairment was related to an additional increase in neural envelope tracking of the target talker, suggesting that hearing impaired adults may have an enhanced sensitivity to envelope modulations or require a larger differential tracking of target versus competing talker to neurally segregate speech from noise. Lastly, both normal-hearing and hearing impaired participants showed an increase in neural envelope tracking with increasing speech understanding. Hence, our results open avenues towards new clinical applications, such as neuro-steered prostheses as well as objective and automatic measurements of speech understanding performance.HighlightsAdults with hearing impairment can neurally segregate speech from background noiseHearing loss is related to enhanced neural envelope tracking of the target talkerNeural envelope tracking has potential to objectively measure speech understanding
Plant species and soil type influence rhizosphere bacterial composition and seedling establishment on serpentine soils
Authors: Igwe Alexandria N. , Vannette Rachel L. 
Published: December 2018

AbstractRoot-associated microbial communities influence plant phenotype, growth and local abundance, yet the factors that structure these microbial communities are still poorly understood. California landscapes contain serpentine soils, which are nutrient-poor and high in heavy metals, and distinct from neighboring soils. Here, we surveyed the rhizoplane of serpentine-indifferent plants species growing on serpentine and non-serpentine soils to determine the relative influence of plant identity and soil chemistry on rhizoplane microbial community structure using 16S rRNA metabarcoding. Additionally, we experimentally examined if locally adapted microorganisms enhance plant growth in serpentine soil. Plant species, soil chemistry, and the interaction between them were important in structuring rhizoplane bacterial communities in both the field and experimental soils. In the experiment, rhizoplane microbial community source influenced seedling survival, but plant growth phenotypes measured were largely invariant to microbial community with a few exceptions. Results from the field sampling suggest that plant species associate with specific microbial communities even across chemically distinct soils, and that microbial communities can differentially influence seedling survival on harsh serpentine soils.
Models of archaic admixture and recent history from two-locus statistics
Authors: Ragsdale Aaron P. , Gravel Simon 
Published: December 2018

AbstractWe learn about population history and underlying evolutionary biology through patterns of genetic polymorphism. Many approaches to reconstruct evolutionary histories focus on a limited number of informative statistics describing distributions of allele frequencies or patterns of linkage disequilibrium. We show that many commonly used statistics are part of a broad family of two-locus moments whose expectation can be computed jointly and rapidly under a wide range of scenarios, including complex multi-population demographies with continuous migration and admixture events. A full inspection of these statistics reveals that widely used models of human history fail to predict simple patterns of linkage disequilibrium. To jointly capture the information contained in classical and novel statistics, we implemented a tractable likelihood-based inference framework for demographic history. Using this approach, we show that human evolutionary models that include archaic admixture in Africa, Asia, and Europe provide a much better description of patterns of genetic diversity across the human genome. We estimate that an unidentified, deeply diverged population admixed with modern humans within Africa both before and after the split of African and Eurasian populations, contributing 4-8% genetic ancestry to individuals in world-wide populations.Author SummaryThroughout human history, populations have expanded and contracted, split and merged, and ex-changed migrants. Because these events affected genetic diversity, we can learn about human history by comparing predictions from evolutionary models to genetic data. Here, we show how to rapidly compute such predictions for a wide range of diversity measures within and across populations under complex demographic scenarios. While widely used models of human history accurately predict common measures of diversity, we show that they strongly underestimate the co-occurence of low frequency mutations within human populations in Asia, Europe, and Africa. Models allowing for archaic admixture, the relatively recent mixing of human populations with deeply diverged human lineages, resolve this discrepancy. We use such models to infer demographic models that include both recent and ancient features of human history. We recover the well-characterized admixture of Neanderthals in Eurasian populations, as well as admixture from an as-yet unknown diverged human population within Africa, further suggesting that admixture with deeply diverged lineages occurred multiple times in human history. By simultaneously testing model predictions for a broad range of diversity statistics, we can assess the robustness of common evolutionary models, identify missing historical events, and build more informed models of human demography.
Macroevolutionary bursts and constraints generate a rainbow in a clade of tropical birds
Authors: Merwin Jon T. , Seeholzer Glenn F. , Smith Brian Tilston 
Published: December 2018

AbstractBackgroundBird plumage exhibits a diversity of colors that serve functional roles ranging from signaling to camouflage and thermoregulation. However, birds must maintain a balance between evolving colorful signals to attract mates, minimizing conspicuousness to predators, and optimizing adaptation to climate conditions. Examining plumage color macroevolution provides a framework for understanding this dynamic interplay over phylogenetic scales. Plumage evolution due to a single overarching process, such as selection, may generate the same macroevolutionary pattern of color variation across all body regions. In contrast, independent processes may partition plumage into sections and produce region-specific patterns. To test these alternative scenarios, we collected color data from museum specimens of an ornate clade of birds, the Australasian lorikeets, using visible-light and UV-light photography, and comparative methods. We predicted that the diversification of homologous feather regions, i.e., patches, known to be involved in sexual signaling (e.g., face) would be less constrained than patches on the back and wings, where new color states may come at the cost of crypsis. Because environmental adaptation may drive evolution towards or away from color states, we tested whether climate more strongly covaried with plumage regions under greater or weaker macroevolutionary constraint.ResultsWe found that alternative macroevolutionary models and varying rates best describe color evolution, a pattern consistent with our prediction that different plumage regions evolved in response to independent processes. Modeling plumage regions independently, in functional groups, and all together showed that patches with similar macroevolutionary models clustered together into distinct regions (e.g., head, wing, belly), which suggests that plumage does not evolve as a single trait in this group. Wing patches, which were conserved on a macroevolutionary scale, covaried with climate more strongly than plumage regions (e.g., head), which diversified in a burst.ConclusionsOverall, our results support the hypothesis that the extraordinary color diversity in the lorikeets was generated by a mosaic of evolutionary processes acting on plumage region subsets. Partitioning of plumage regions in different parts of the body provides a mechanism that allows birds to evolve bright colors for signaling and remain hidden from predators or adapt to local climatic conditions.
Binning microbial genomes using deep learning
Authors: Nissen Jakob Nybo , Sønderby Casper Kaae , Armenteros Jose Juan Almagro , Grønbech Christopher Heje , Bjørn Nielsen Henrik , Petersen Thomas Nordahl , Winther Ole , Rasmussen Simon 
Published: December 2018

AbstractIdentification and reconstruction of microbial species from metagenomics wide genome sequencing data is an important and challenging task. Current existing approaches rely on gene or contig co-abundance information across multiple samples andk-mer composition information in the sequences. Here we use recent advances in deep learning to develop an algorithm that uses variational autoencoders to encode co-abundance and compositional information prior to clustering. We show that the deep network is able to integrate these two heterogeneous datasets without any prior knowledge and that our method outperforms existing state-of-the-art by reconstructing 1.8 - 8 times more highly precise and complete genome bins from three different benchmark datasets. Additionally, we apply our method to a gene catalogue of almost 10 million genes and 1,270 samples from the human gut microbiome. Here we are able to cluster 1.3 - 1.8 million extra genes and reconstruct 117 - 246 more highly precise and complete bins of which 70 bins were completely new compared to previous methods. Our method Variational Autoencoders for Metagenomic Binning (VAMB) is freely available at:https://github.com/jakobnissen/vamb
Reactive/proactive aggression specific cortical and subcortical alterations in children and adolescents with disruptive behavior
Authors: Naaijen Jilly , Mulder Leandra M , Ilbegi Shahrzad , Bruijn Sanne de , Kleine-Deters Renee , Dietrich Andrea , Hoekstra Pieter J , Marsman Jan-Bernard C , Aggensteiner Pascal M , Holz Nathalie E , Boettinger Boris , Baumeister Sarah , Banaschewski Tobias , Saam Melanie C , Schulze Ulrike M E , Santosh Paramala J , Sagar-Ouriaghli Ilyas , Mastroianni Mathilde , Fornieles Josefina Castro , Bargallo Nuria , Rosa Mireia , Arango Celso , Penzol Maria J , Werhahn Julia E , Walitza Susanne , Brandeis Daniel , Glennon Jeffrey C , Franke Barbara , Zwiers Marcel P , Buitelaar Jan K 
Published: December 2018

AbstractObjectiveMaladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated this association in predefined regions of interest.MethodT1-weighted magnetic resonance images were acquired from 158 children and adolescents with aggressive behavior (ODD/CD) and 96 controls in a multi-centre study. Aggression subtypes were assessed by questionnaires. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models.ResultsIn cases only proactive aggression was negatively associated with amygdala volume (b=−11.82, p=0.05), while reactive aggression was negatively associated with insula volume (b=−46.41, p=0.01). Classical group comparison showed that children and adolescents with aggressive behavior had smaller volumes than controls in (bilateral) ventral striatum (p=0.003), ACC (p=0.01), and vmPFC (p=0.003) with modest effect sizes.ConclusionsAggression was associated with reduced volume in brain regions involved in decision making. Negative associations were found between reactive aggression and volumes in regions involved in threat responsivity and between proactive aggression and regions linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure.
Wolbachia, Cardinium and climate: an analysis of global data
Authors: Charlesworth J. , Weinert L. A. , Araujo-Jnr. E. V. , Welch J. J. 
Published: December 2018

AbstractBacterial secondary symbionts are very common in terrestrial arthropods, but infection levels vary widely among populations. Experiments and within-species comparisons both suggest that environmental temperature might be important in explaining this variation. To investigate the importance of temperature, at broad geographical and taxonomic scales, we extended a global database of terrestrial arthropods screened for Wolbachia and Cardinium. Our final data set contained data from 114,297 arthropods (>2,500 species) screened for Wolbachia and 17,011 arthropods (>800 species) screened for Cardinium, including population samples from 137 different countries, and with mean temperatures varying from - 6.5 to 29.2°C. In insects and relatives, Cardinium infection showed a clear and consistent tendency to increase with temperature. For Wolbachia, a tendency to increase with temperature in temperate climates, is counteracted by reduced prevalence in the tropics, resulting in a weak negative trend overall. We discuss the implications of these results for natural and introduced symbionts, in regions affected by climate change.
Retinoid X receptor alpha is a spatiotemporally-specific therapeutic target for doxorubicin-induced cardiomyopathy in adult zebrafish
Authors: Ma Xiao , Ding Yonghe , Zhang Hong , Qiu Qi , Dvornikov Alexey V. , Kim Maengjo , Wang Yong , Lowerison Matthew , Herrmann Joerg , Ekker Stephen C. , Hsiai Tzung K. , Lin Xueying , Xu Xiaolei 
Published: December 2018

AbstractWhile the genetic suppressor screen is efficient in suggesting therapeutic genes, this strategy has yet to be successful for cardiomyopathies in vertebrates. To develop such a strategy, we recently established a mutagenesis screen platform in zebrafish for systematic discovery of genetic modifiers of doxorubicin-induced cardiomyopathy (DIC). Here, we further revealed both molecular and cellular insights of the first salutary modifier emerged from the screen, i.e.gene-breaking transposon(GBT)0419that affects theretinoid X receptor alpha a(rxraa) gene. First, by rescuing the mutation in tissue-specific manner with multiple Cre-loxP systems, we demonstrated that the endothelial, but not myocardial or epicardial, function ofrxraais primary to this cardioprotective effects. Next, we showed that therxraa-associated salutary effects on DIC were conferred partially by the activation of retinoid acid (RA) signaling. Finally, we identified isotretinoin and bexarotene, 2 US Food and Drug Administration-approved RXRA agonists that are effective in treating adult zebrafish DIC when administered during the early, but not the late, phase of DIC progression. Collectively, we provided the firstin vivogenetic evidence in supportingRXRAas the therapeutic target for DIC, and uncovered a previously unrecognized spatiotemporally-restricted mechanism for this gene-based therapeutic strategy. Our study also justified that searching salutary modifiers via zebrafish mutagenesis screen can be effective in discovering new therapeutic targets for cardiomyopathies.
CarbMetSim:A discrete-event simulator for carbohydrate metabolism in humans
Authors: Goyal Mukul , Aydas Buket , Ghazaleh Husam , Rajasekharan Sanjay 
Published: December 2018

AbstractThis paper describesCarbMetSim, adiscrete-eventsimulator that tracks the blood glucose level of a person in response to a timed sequence of diet and exercise activities.CarbMetSimimplements broader aspects of carbohydrate metabolism in human beings with the objective of capturing the average impact of various diet/exercise activities on the blood glucose level. Key organs (stomach, intestine, portal vein, liver, kidney, muscles, adipose tissue, brain and heart) are implemented to the extent necessary to capture their impact on the production and consumption of glucose. Key metabolic pathways (glucose oxidation, glycolysisandgluconeogenesis) are accounted for in the operation of different organs. The impact of insulin and insulin resistance on the operation of various organs and pathways is captured in accordance with published research.CarbMetSimprovides broad flexibility to configure the insulin production ability, the average flux along various metabolic pathways and the impact of insulin resistance on different aspects of carbohydrate metabolism. The simulator does not yet have a detailed implementation of protein and lipid metabolism.