bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homeostatic changes maintain the gain control of spinal motoneurones across the lifetime of C57BL/6J mice
Authors: Goltash S , Jensen MH , Dimintiyanova KP , Jensen DB , Lehnhoff J , Moldovan M , Meehan CF 
Published: May 2022

ABSTRACTAge-related changes in the excitability of spinal motoneurone have been observed in mouse models of neurodegenerative diseases affecting these neurones. How the excitability of spinal motoneurones change with healthy ageing in mice and how this compares with that seen in neurodegenerative diseases is unknown. Therefore, we performed in vivo intracellular recording from identified spinal motoneurones in C57BL/6 mice at three different ages (100, 300-400 and 600-750 days old). Behavioral tests confirmed a linear reduction in motor function across these ages (using the rotorod test).Significant differences were observed with respect to the features of individual somatic action potential with ageing including a decreased rate of rise and fall in aged mice. Surprisingly, the rate of rise of the action potential at the initial segment was altered in middle aged mice. Immunohistochemical labelling of the axon initial segment of the motoneurones confirmed structural changes occurring at middle age (decreased length and diameter) but returning to the earlier parameters in aged mice. To explore the effects on repetitive firing, this was tested across the age groups which showed surprising little difference as the mice aged, with a similar rheobase and I-f gain across all age groups (with the exception of a lower voltage threshold for action potential initiation in middle-aged mice). However, amplitudes of the after-hyperpolarization and the input resistance were both found to be significantly altered with age.We conclude that there are changes occurring in the intrinsic properties of spinal motoneurones that control their excitability over the lifetime of mice, although these do not develop in a linear fashion from young to old. We propose that these changes are homeostatic in nature and are able to compensate for one another to maintain a constant gain control across the lifetime.
An electrogenetic toggle switch design
Authors: Grozinger Lewis , Heidrich Elizabeth , Goñi-Moreno Ángel 
Published: May 2022

AbstractSynthetic biology uses molecular biology to implement genetic circuits that perform computations. These circuits can process inputs and deliver outputs according to predefined rules that are encoded, often entirely, into genetic parts. However, the field has recently begun to focus on using mechanisms beyond the realm of genetic parts for engineering biological circuits. We analyse the use of electrogenic processes for circuit design and present a model for a merged genetic and electrogenetic toggle switch. Computational simulations explore conditions under which bistability emerges in order to identify the circuit design principles for best switch performance. The results provide a basis for the rational design and implementation of hybrid devices that can be measured and controlled both genetically and electronically.
Higher-order interactions shape microbial interactions as microbial community complexity increases
Authors: Morin Manon A. , Morrison Anneliese J. , Harms Michael J. , Dutton Rachel J. 
Published: May 2022

ABSTRACTNon-pairwise interactions, or higher-order interactions (HOIs), in microbial communities have been claimed to explain the emergent features in microbiomes. Yet, the re-organization of microbial interactions between pairwise cultures and larger communities remains largely unexplored from a molecular perspective but is central to our understanding and further manipulation of microbial communities. Here, we used a bottom-up approach to investigate microbial interaction mechanisms from pairwise cultures up to 4-species communities from a simple microbiome (Hafnia alvei, Geotrichum candidum, Pencillium camemberti and Escherichia coli). Specifically, we characterized the interaction landscape for each species combination involving E. coli by identifying E. coli’s interaction-associated genes using an RB-TnSeq-based interaction assay. We observed a deep reorganization of the interaction-associated genes, with very few 2-species interactions conserved all the way up to a 4-species community and the emergence of multiple HOIs. We further used a quantitative genetics strategy to decipher how 2-species interactions were quantitatively conserved in higher community compositions. Epistasis-based analysis revealed that, of the interactions that are conserved at all levels of complexity, 82% follow an additive pattern. Altogether, we demonstrate the complex architecture of microbial interactions even within a simple microbiome, and provide a mechanistic and molecular explanation of HOIs.
High-resolution neural recordings improve the accuracy of speech decoding
Authors: Duraivel Suseendrakumar , Rahimpour Shervin , Chiang Chia-Han , Trumpis Michael , Wang Charles , Barth Katrina , Lad Shivanand P. , Friedman Allan H. , Southwell Derek G. , Sinha Saurabh R. , Viventi Jonathan , Cogan Gregory 
Published: May 2022

AbstractPatients suffering from debilitating neurodegenerative diseases often lose the ability to communicate, detrimentally affecting their quality of life. One promising solution to restore communication is to decode signals directly from the brain to enable neural speech prostheses. However, decoding has been limited by coarse neural recordings which inadequately capture the rich spatio-temporal structure of human brain signals. To resolve this limitation, we performed novel, high-resolution, micro-electrocorticographic (μECoG) neural recordings during intra-operative speech production. We obtained neural signals with 57× higher spatial resolution and 48% higher signal-to-noise ratio compared to standard invasive recordings. This increased signal quality improved phoneme decoding by 35% compared to standard intracranial signals. Accurate decoding was dependent on the high-spatial resolution of the neural interface. Non-linear decoding models designed to utilize enhanced spatio-temporal neural information produced better results than linear techniques. We show for the first time that μECoG can enable high-quality speech decoding, demonstrating its ability to improve neural interfaces for neural speech prostheses.
Multivariate optimization of k for k-nearest-neighbor feature selection with dichotomous outcomes: complex associations, class imbalance, and application to RNA-Seq in Major Depressive Disorder
Authors: Dawkins Bryan A. , McKinney Brett A. 
Published: May 2022

ABSTRACTOptimization of nearest-neighbor feature selection depends on the number of samples and features, the type of statistical effect, the feature scoring algorithm, and class imbalance. We recently reported a fixed-k for Nearest-neighbor Projected-Distance Regression (NPDR) that addresses each of these parameters, except for class imbalance. To remedy this, we parameterize our NPDR fixed-k by the minority class size (minority-class-k). We also introduce a class-adaptive fixed-k (hit-miss-k) to improve performance of Relief-based algorithms on imbalanced data. In addition, we present two optimization methods, including constrained variable-wise optimized k (VWOK) and a fixed-k derived with principal components analysis (kPCA), both of which are adaptive to class imbalance. Using simulated data, we show that our methods significantly improve feature detection across a variety of nearest-neighbor feature scoring metrics, and we demonstrate superior performance in comparison to random forest and ridge regression using consensus-nested cross-validation (cnCV) for feature selection. We applied cnCV to RNASeq expression data from a study of Major Depressive Disorder (MDD) using NPDR with minority-class-k, random forest, and cnCV-ridge regression for gene importance. Pathway analysis showed that NPDR with minority-class-k alone detected genes with clear relevance to MDD, suggesting that our new fixed-k formula is an effective rule-of-thumb.
Semi-field and surveillance data define the natural diapause timeline forCulex pipiensacross the United States
Authors: Field Eleanor N. , Shepard John J. , Clifton Mark E. , Price Keith J. , Witmier Bryn J. , Johnson Kirk , Boze Broox , Abadam Charles , Ebel Gregory D. , Armstrong Philip M. , Barker Christopher M. , Smith Ryan C. 
Published: May 2022

AbstractCulex pipiensis a globally-distributed mosquito of medical and veterinary importance, serving as a primary vector of West Nile virus (WNV). To survive winter, femaleCx. pipiensmosquitoes undergo adult reproductive diapause initiated by photoperiod and temperature cues. While well-studied under laboratory conditions, the environmental signals that promoteCx. pipiensdiapause induction in natural settings are less understood. Here, we evaluateCx. pipiensin laboratory and semi-field studies to examine diapause induction, defining an approximate timeline beginning in late-August where mosquitoes become receptive to diapause. Using gravid (reproductive) mosquito surveillance data as a proxy for adult diapause incidence for locations across the United States (California, Colorado, Connecticut, Illinois, Iowa, Minnesota, Pennsylvania, and Virginia), we demonstrate consistent population declines coinciding with periods of diapause receptivity except in hybridization zones whereCx. quinquefasciatusis present, suggesting thatCulexpopulation genetics can significantly impact end-season population trends. Together, this study defines a window for diapause induction across the United States, shaped by temperature, latitude, elevation, and mosquito population genetics. Coinciding with the cessation of WNV activity, these data can have important implications for mosquito control, where targeted efforts prior to diapause induction can decrease mosquito populations and WNV overwintering to reduce mosquito-borne disease incidence the following season.
Predictive Sequence Learning in the Hippocampal Formation
Authors: Chen Yusi , Zhang Huanqiu , Cameron Mia , Sejnowski Terrrence 
Published: May 2022

SummaryThe hippocampus receives sequences of sensory inputs from the cortex during exploration and encodes the sequences with millisecond precision. We developed a predictive autoencoder model of the hippocampus including the trisynaptic and monosynaptic circuits from the entorhinal cortex (EC). CA3 was trained as a self-supervised recurrent neural network to predict its next input. We confirmed that CA3 is prediction ahead by analyzing the spike coupling between simultaneously recorded neurons in the dentate gyrus, CA3 and CA1 of the mouse hippocampus. In the model, CA1 neurons signal prediction errors by comparing the prediction from CA3 to the next input directly from the EC. The model exhibits the rapid appearance and the slow fading of CA1 place cells, and displays replay and phase precession from CA3. The model could be learnt in a biologically plausible way with the help of error-encoding neurons. Similarities between the circuits in the hippocampus and thalamocortical circuits suggest that such computation motif could also underlie self-supervised sequence learning in the cortex.
The limitations of phenotype prediction in metabolism
Authors: Yubero Pablo , Lavin Alvar A. , Poyatos Juan F. 
Published: May 2022

ABSTRACTPhenotype prediction is at the core of many questions in biology. Prediction is frequently attained by determining statistical associations between genetic and phenotypic variation, ignoring the exact processes causing the phenotype. Here, we present a framework based on genome-scale metabolic reconstructions to reveal the mechanisms behind the associations. We compute a polygenic score (PGS) that identifies a set of enzymes as predictors of growth, the phenotype. This set arises from the synergy of the functional mode of metabolism in a particular environment and its evolutionary history, and is transportable to infer the phenotype across a range of environments. We also find that there exists an optimal genetic variation for predictability and demonstrate how the linear PGS can yet explain phenotypes generated by the underlying nonlinear biochemistry. Thus, the explicit model interprets the black-box statistical associations of the genotype-to-phenotype map and helps uncover what limits prediction in metabolism.
Exploring the mosquito-arbovirus network: a survey of vector competence experiments
Authors: Chen Binqi , Sweeny Amy R. , Wu Velen Yifei , Christofferson Rebecca , Ebel Gregory , Fagre Anna C. , Gallichotte Emily , Kading Rebekah , Ryan Sadie J. , Carlson Colin J. 
Published: May 2022

AbstractArboviruses receive heightened research attention during major outbreaks, or when they cause unusual or severe clinical disease, but are otherwise under-characterized. Global change is also accelerating the emergence and spread of arboviral diseases, leading to time sensitive questions about potential interactions between viruses and novel vectors. Vector competence experiments help determine the susceptibility of certain arthropods to a given arbovirus, but these experiments are often conducted in real-time during outbreaks, rather than with preparedness in mind. We conducted a systematic review of reported mosquito-arbovirus competence experiments, screening 570 abstracts to arrive at 265 studies testing in vivo arboviral competence. We found that over 90% of potential mosquito-virus combinations are untested in experimental settings, and that entire regions and their corresponding vectors and viruses are undersampled. These knowledge gaps stymie outbreak response, and limit attempts to both build and validate predictive models of the vector-virus network.
Fetal imidacloprid causes ASD-like impairment of biological motion perception in neonatal chicks
Authors: Matsushima Toshiya , Miura Momoko , Patzke Nina , Toji Noriyuki , Wada Kazuhiro , Ogura Yukiko , Homma Koichi J. , Sgadò Paola , Vallortigara Giorgio 
Published: May 2022

AbstractSeveral environmental chemicals are suspected as risk factors for autism spectrum disorder (ASD), including valproic acid (VPA) and pesticides acting on nicotinic acetylcholine receptor (nAChR) if exposed during pregnancy. However, their target processes in fetal neuro-development are unspecified. We report that fetal injection of VPA impaired the imprinting of an artifact object in hatchlings, while the predisposed preference to biological motion (BM) remained intact. Blockade of nAChR acted oppositely, namely, spared imprinting and impaired BM in chicks. Beside ketamine and tubocurarine, significant effects of imidacloprid (a neonicotinoid insecticide) appeared at dose ≤1ppm. Despite the distinct processes, both VPA and nAChR blockade similarly impaired imprinting of biological image composed of point-light animation. Furthermore, both impairments were rescued by post-natal bumetanide treatment, suggesting common pathology underlying the social attachment malformation. Ambient neonicotinoid could hinder adaptive socialization through impaired development of visual perception in early neonates.
Age-specific and Sex-specific Nectar and Pollen Use by a Butterfly Pollinator
Authors: Boggs Carol L. , Iyengar Vikram 
Published: May 2022

AbstractAge-specific patterns of nectar and pollen use by insect pollinators may reflect behavioral or physiological changes over the insect’s lifespan, and may also influence flower visitation rate. Studying Heliconius charithonia (Lepidoptera: Nymphalidae) and Psiguria umbrosa (Cucurbitaceae), we showed that honey-water (as a nectar substitute) intake increases over the first ten to twelve days of female’s life, while decreasing over the same age period for males, when individuals were fed ad libitum. Intake then remains stable at least through 28 days of age. Mean intake is higher for females than for males, and is not significantly affected by body size. Intake patterns for honey-water and pollen did not change with age in a similar manner. Pollen feeding increased significantly with age for both sexes, with females showing a two week delay in the increase when studied in a free-flying greenhouse population with competition for pollen. Under both ad libitum and pollen competition conditions, females collected more pollen than did males. Body size did not significantly affect the amount of pollen collected for either sex. Within each sex, butterflies with ad libitum pollen collected more pollen than those in a free-flying greenhouse population with more restricted pollen availability. These results suggest that two resources obtained from the same source, pollen and nectar, are not treated identically by the insect pollinator, and that the demography of the insect population may affect flower visitation rates in some cases. Further, foraging patterns for pollen and nectar are likely driven by physiological demand for different resource types.
Novel insights into the pig gut microbiome using metagenome-assembled genomes
Authors: Holman Devin B. , Kommadath Arun , Tingley Jeffrey P. , Abbott D. Wade 
Published: May 2022

AbstractPigs are among the most numerous and intensively farmed food-producing animals in the world. The gut microbiome plays an important role in the health and performance of swine and changes rapidly after weaning. Here, fecal samples were collected from pigs at 7 different times points from 7 to 140 days of age. These swine fecal metagenomes were used to assemble 1,150 dereplicated metagenome-assembled genomes (MAGs) that were at least 90% complete and had less than 5% contamination. These MAGs represented 472 archaeal and bacterial species, and the most widely distributed MAGs were the uncultured species Collinsella sp002391315, Sodaliphilus sp004557565, and Prevotella sp000434975. Weaning was associated with a decrease in the relative abundance of 69 MAGs (e.g. Escherichia coli) and an increase in the relative abundance of 140 MAGs (e.g. Clostridium sp000435835, Oliverpabstia intestinalis). Genes encoding for the production of the short-chain fatty acids acetate, butyrate, and propionate were identified in 68.5%, 18.8%, and 8.3% of the MAGs, respectively. Carbohydrate-active enzymes associated with the degradation of arabinose oligosaccharides and mixed-linkage glucans were predicted to be most prevalent among the MAGs. Antimicrobial resistance genes were detected in 327 MAGs, including 59 MAGs with tetracycline resistance genes commonly associated with pigs such as tet(44), tet(Q), and tet(W). Overall, 82% of the MAGs were assigned to species that lack cultured representatives indicating that a large portion of the swine gut microbiome is still poorly characterized. The results here also demonstrate the value of MAGs in adding genomic context to gut microbiomes.ImportanceMany of the bacterial strains found in the mammalian gut are difficult to culture and isolate due to their various growth and nutrient requirements that are frequently unknown. Here, we assembled strain-level genomes from short metagenomic sequences, so-called metagenome-assembled genomes (MAGs), that were derived from fecal samples collected from pigs at multiple time points. The majority of these MAGs represented bacterial species that have yet to be cultured or described thus underlining the need for cultivation studies that isolate and describe novel bacterial species. The genomic context of a number of antimicrobial resistance genes commonly detected in swine was also determined. In addition, our study connected taxonomy with potential metabolic functions such as carbohydrate degradation and short-chain fatty acid production.
Does directly integrating health information exchange (HIE) data with the electronic health record increase HIE use by clinicians in the emergency department?
Authors: Hosler Heidi , Jang Jeong Hoon , Schaffer Jason T. , Price John , Schleyer Titus K. , Rivera Rebecca L. 
Published: May 2022

ABSTRACTObjectiveDevelop and evaluate the effect of a Fast Healthcare Interoperability Resources (FHIR) app, Health Dart, integrating information from Indiana’s community health information exchange (HIE), the Indiana Network for Patient Care (INPC), directly with Cerner, an electronic health record (EHR)Materials and MethodsHealth Dart was implemented in 14 Indiana University Health emergency departments (ED) using a stepped-wedge study design. We analyzed rates of INPC use in 286,175 ED encounters between October 1, 2019 and December 31, 2020. Logistic regression was used to model the probability of INPC use given the implementation context, such as user interface (UI) enhancements and the COVID-19 pandemic.ResultsINPC use increased by 131% across all encounters (from 3.6% to 8.3%; p<0.001) after Health Dart implementation. INPC use increased by144% (from 3.6% to 8.8%; p<0.001) more than two months post-implementation. After UI enhancements, post-implementation INPC use increased 123% (from 3.5% to 7.8%) compared to 181% (from 3.6% to 10.1%; p<0.001) in post-implementation encounters that occurred before UI enhancements. During the pandemic, post-implementation INPC use increased by 135% (from 3.4% to 8.0%; p<0.001) compared to 178% (from 3.6% to 10%; p<0.001) in post-implementation encounters that occurred before the pandemic. Statistical significance was determined using 95% confidence intervals (α=0.05).DiscussionDirect integration of HIE information into an EHR substantially increased frequency of HIE use, but the effect was weakened by the UI enhancements and pandemic.ConclusionHIE information integrated into EHRs in the form of dashboards can potentially make information retrieval more efficient and effective for clinicians.
MSM with HIV: Improving prevalence and risk estimates by a Bayesian small area estimation modelling approach for public health service areas in the Netherlands
Authors: Wang Haoyi , den Daas Chantal , de Coul Eline Op , Jonas Kai J 
Published: May 2022

AbstractIn many countries, HIV infections among MSM (MSMHIV) are closely monitored, and updated epidemiological reports are made available annually, yet the true prevalence of MSMHIV can be masked for areas with small population density or lack of data. Therefore, this study aimed to investigate the feasibility of small area estimation with a Bayesian approach to improve HIV surveillance. Data from the European MSM Internet Survey 2017 (EMIS-2017, Dutch subsample, n=3,459) and the Dutch survey ‘Men & Sexuality-2018’ (SMS-2018, n=5,653) were utilized in this study. We first applied a frequentist calculation to compare the observed relative risk of MSMHIV per Public Health Services (GGD) region in the Netherlands. We then applied a Bayesian spatial analysis and ecological regression to account for variance due to space and determinants associated with HIV among MSM to obtain more robust estimates. Results of the prevalence and risk estimations from EMIS-2017 and SMS-2018 converged with minor differences. Both estimations confirmed that the risk of MSMHIV is heterogenous across the Netherlands with some GGD regions, such as GGD Amsterdam [RR=1.21 (95% credible interval 1.05-1.38) by EMIS-2017; RR=1.39 (1.14-1.68) by SMS-2018], having a higher-than-average risk. Results from our ecological regression modelling revealed significant regional determinants which can impact on the risk for MSMHIV. In sum, our Bayesian approach to assess the risk of HIV among MSM was able to close data gaps and provide more robust prevalence and risk estimations. It is feasible and directly applicable for future HIV surveillance as a statistical adjustment tool.