bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast and accurate annotation of acoustic signals with deep neural networks
Authors: Steinfath Elsa , Palacios Adrian , Rottschäfer Julian R , Yuezak Deniz , Clemens Jan 
Published: March 2021

AbstractAcoustic signals serve communication within and across species throughout the animal kingdom. Studying the genetics, evolution, and neurobiology of acoustic communication requires annotating acoustic signals: segmenting and identifying individual acoustic elements like syllables or sound pulses. To be useful, annotations need to be accurate, robust to noise, and fast.We here introduceDAS, a method that annotates acoustic signals across species based on a deep-learning derived hierarchical presentation of sound. We demonstrate the accuracy, robustness, and speed ofDASusing acoustic signals with diverse characteristics from insects, birds, and mammals.DAScomes with a graphical user interface for annotating song, training the network, and for generating and proofreading annotations. The method can be trained to annotate signals from new species with little manual annotation and can be combined with unsupervised methods to discover novel signal types.DASannotates song with high throughput and low latency, allowing realtime annotations for closed-loop experimental interventions. Overall,DASis a universal, versatile, and accessible tool for annotating acoustic communication signals.
High Gamma and Beta Temporal Interference Stimulation in the Human Motor Cortex Improves Motor Functions
Authors: Ma Ru , Xia Xinzhao , Zhang Wei , Lu Zhuo , Wu Qianying , Cui Jiangtian , Song Hongwen , Fan Chuan , Chen Xueli , Wei Junjie , Ji Gongjun , Wang Kai , Wang Xiaoxiao , Qiu Bensheng , Zhang Xiaochu 
Published: March 2021

ABSTRACTBackgroundTemporal interference (TI) stimulation is a new technique of noninvasive brain stimulation. Envelope-modulated waveforms with two high-frequency carriers can activate neurons in target brain regions without stimulating the overlying cortex, which has been validated in mouse brains. However, whether TI stimulation can work on the human brain has not been elucidate.ObjectiveTo assess the effectiveness and safety aspect of the envelope-modulated waveform of TI stimulation on human primary motor cortex (M1).MethodsParticipants attended three sessions of 30-min TI stimulation at 2 mA during a random reaction time task (RRTT) or a serial reaction time task (SRTT). Motor cortex excitability was measured before and after TI stimulation.ResultsIn the RRTT experiment, only 70 Hz TI stimulation had a promoting effect on the reaction time (RT) performance and excitability of the motor cortex compared to sham stimulation. Meanwhile, compared with the sham condition, only 20 Hz TI stimulation significantly facilitated motor learning in the SRTT experiment, which was significantly positively correlated with the increase in motor evoked potential.ConclusionThese results indicate that the envelope-modulated waveform of TI stimulation has a significant promoting effect on human motor functions, experimentally suggesting the effectiveness of TI stimulation in humans for the first time and pave the way for further explorations.
Association of stress-related neural activity and baseline interleukin-6 plasma levels in healthy adults
Authors: Voges Johanna F. , Müller-Pinzler Laura , Neis Miriam , Luebber Finn , Lange Tanja , Hundt Jennifer E. , Kasten Meike , Krämer Ulrike M. , Krach Sören , Rademacher Lena 
Published: March 2021

AbstractSeveral studies suggest a link between acute changes in inflammatory parameters due to an endotoxin or (psychological) stressor and the brain’s stress response. The extent to which basal circulating levels of inflammatory markers are associated with the brain’s stress response has been hardly investigated so far. In the present study, baseline plasma levels of the cytokine interleukin (IL)-6 were obtained and linked to neural markers of psychosocial stress using a modified version of the Montreal Imaging Stress Task in a sample of N=65 healthy subjects (N=39 female). Of three a-priori defined regions of interest – the amygdala, anterior insula, and anterior cingulate cortex – baseline IL-6 was significantly and negatively associated with stress-related neural activation in the right amygdala and left anterior insula. Our results suggest that baseline cytokines might be related to differences in the neural stress response and that this relationship could be inverse to that previously reported for induced acute changes in inflammation markers.
Gene Expression Variation in Arabidopsis Embryos at Single-Nucleus Resolution
Authors: Kao Ping , Schon Michael A. , Mosiolek Magdalena , Nodine Michael D. 
Published: March 2021

AbstractSoon after fertilization of egg and sperm, plant genomes become transcriptionally activated and drive a series of coordinated cell divisions to form the basic body plan during embryogenesis. Early embryonic cells rapidly diversify from each other, and investigation of the corresponding gene expression dynamics can help elucidate underlying cellular differentiation programs. However, current plant embryonic transcriptome datasets either lack cell-specific information or have RNA contamination from surrounding non-embryonic tissues. We have coupled fluorescence-activated nuclei sorting together with single-nucleus mRNA sequencing to construct a gene expression atlas ofArabidopsis thalianaearly embryos at single-cell resolution. In addition to characterizing cell-specific transcriptomes, we found evidence that distinct epigenetic and transcriptional regulatory mechanisms operate across emerging embryonic cell types. These datasets and analyses, as well as the approach we devised, are expected to facilitate the discovery of molecular mechanisms underlying pattern formation in plant embryos.Summary statementA transcriptome atlas of Arabidopsis embryos constructed from single nuclei reveals cell-specific epigenetic and transcriptional regulatory features.
Dynamic bi-directional phosphorylation events associated with the reciprocal regulation of synapses during homeostatic up- and down-scaling
Authors: Desch Kristina , Langer Julian D. , Schuman Erin M. 
Published: March 2021

SummaryHomeostatic synaptic scaling allows for bi-directional adjustment of the strength of synaptic connections in response to changes in their input. Protein phosphorylation modulates many neuronal and synaptic processes, but it has not been studied on a global, proteome-wide scale during synaptic scaling. To examine this, we used LC-MS/MS analyses to measure changes in the phosphoproteome in response to up- or down-scaling in cultured cortical neurons over minutes to 24 hours. Out of 45,000 phosphorylation events measured, ~3,300 (associated with 1,280 phospho-proteins) were regulated by homeostatic scaling. The activity-sensitive phosphoproteins were predominantly located at synapses and involved in cytoskeletal reorganization. We identified many early transient phosphorylation events which could serve as sensors for the activity offset as well as late and/or persistent phosphoregulation that could represent effector mechanisms driving the homeostatic response. Much of the persistent phosphorylation was reciprocally regulated by up- or down-scaling, suggesting that the mechanisms underlying these two poles of synaptic regulation make use of a common signaling axis.
Bias correction for inverse variance weighting Mendelian randomization
Authors: Mounier Ninon , Kutalik Zoltán 
Published: March 2021

AbstractInverse-variance weighted two-sample Mendelian randomization (IVW-MR) is the most widely used approach that utilizes genome-wide association studies (GWAS) summary statistics to infer the existence and the strength of the causal effect between an exposure and an outcome. Estimates from this approach can be subject to different biases due to the use of weak instruments and winner’s curse, which can change as a function of the overlap between the exposure and outcome samples.We developed a method (MRlap) that simultaneously considers weak instrument bias and winner’s curse, while accounting for potential sample overlap. Assuming spike-and-slab genomic architecture and leveraging LD-score regression and other techniques, we could analytically derive, reliably estimate, and hence correct for the bias of IVW-MR using association summary statistics only.We tested our approach using simulated data for a wide range of realistic settings. In all the explored scenarios, our correction reduced the bias, in some situations by as much as 30 folds. Additionally, our results are consistent with the fact that the strength of the biases will decrease as the sample size increases and we also showed that the overall bias is also dependent on the genetic architecture of the exposure, and traits with low heritability and/or high polygenicity are more strongly affected. ApplyingMRlapto obesity-related exposures revealed significant differences between IVW-based and corrected effects, both for non-overlapping and fully overlapping samples.Our method not only reduces bias in causal effect estimation but also enables the use of much larger GWAS sample sizes, by allowing for potentially overlapping samples.
MLG: Multilayer graph clustering for multi-condition scRNA-seq data
Authors: Lu Shan , Conn Daniel J. , Chen Shuyang , Johnson Kirby D. , Bresnick Emery H. , Keleş Sündüz 
Published: March 2021

AbstractSingle-cell transcriptome sequencing (scRNA-seq) enabled investigations of cellular heterogeneity at exceedingly higher resolutions. Identification of novel cell types or transient developmental stages across multiple experimental conditions is one of its key applications. Linear and non-linear dimensionality reduction for data integration became a foundational tool in inference from scRNA-seq data. We presentMultiLayerGraph Clustering (MLG) as an integrative approach for combining multiple dimensionality reduction of multi-condition scRNA-seq data. MLG generates a multilayer shared nearest neighbor cell graph with higher signal-to-noise ratio and outperforms current best practices in terms of clustering accuracy across large-scale bench-marking experiments. Application of MLG to a wide variety of datasets from multiple conditions highlights how MLG boosts signal-to-noise ratio for fine-grained sub-population identification. MLG is widely applicable to settings with single cell data integration via dimension reduction.
Flow cytometry-based determination of ploidy from dried leaf specimens in genomically complex collections of the tropical forage grass Urochloa s. l
Authors: Tomaszewska Paulina , Pellny Till K. , Hernández Luis Miguel , Mitchell Rowan A. C. , Castiblanco Valheria , de Vega José J. , Schwarzacher Trude , Heslop-Harrison Pat (J.S.) 
Published: March 2021

AbstractWe aimed to develop an optimized approach to determine ploidy for dried leaf material in a germplasm collection of a tropical forage grass group, including approaches to collect, dry and preserve plant samples for flow cytometry analysis. Urochloa (including Brachiaria, Megathyrus and some Panicum) tropical grasses are native to Africa and are now, after selection and breeding, planted worldwide, particularly in South America, as important forages with huge potential for further sustainable improvement and conservation of grasslands. The methods enable robust identification of ploidy levels (coefficient of variation, CV, typically <5%). Ploidy of some 353 forage grass accessions (ploidy range from 2 to 9), from international genetic resource collections, showing variation in basic chromosome numbers and reproduction modes (apomixis and sexual), were determined using our defined standard protocol. Two major Urochloa agamic complexes used in the current breeding programs at CIAT and EMBRAPA: the ‘brizantha’ and ‘humidicola’ agamic complexes are variable, with multiple ploidy levels and DNA content. U. brizantha has odd level of ploidy (x=5), and the relative differences in nuclear DNA content between adjacent cytotypes is reduced, thus more precise examination of this species is required. Ploidy measurement of U. humidicola revealed some aneuploidy.
Silk-based antimicrobial peptide mixed with recombinant spidroin creates functionalized spider silk
Authors: Liu Frank Y.C. 
Published: March 2021

1.AbstractSurgical site infection (SSI) from sutures is a global health emergency because of the antibiotic crisis. Methicillin-resistant S. aureus and other emerging strains are difficult to treat with antibiotics, so drug-free sutures with antimicrobial properties are a solution. Functionalized spider silk protein (spidroin) is a candidate for its extraordinary strength because it has a large repetitive region (150Rep) that forms crosslinked beta-sheets. The antimicrobial peptide HNP-1 can be connected to recombinant spidroin to create antimicrobial silk. Ni-NTA purified 2Rep-HNP1 fusion protein was mixed with recombinant NT2RepCT spidroin at 1:25, 1:20, 1:10 ratios, and spun into silk fibers by syringe-pumping protein into a 100% isopropanol bath. Beta-sheet crosslinking of the identical 2Rep regions tagged the 2Rep-HNP1 permanently onto the resultant silk. Silk showed no sign of degradation in an autoclave, PBS, or EtOH. The tagged 2Rep-HNP1 retained broad-spectrum antimicrobial activity >90% against S. aureus and E. coli as measured by log reduction and radial diffusion assay. Furthermore, a modified expression protocol increased protein yield of NT2RepCT 2.8-fold, and variable testing of the spinning process demonstrated the industrial viability of silk production. We present a promising suture alternative in antimicrobial recombinant spider silk.
Neonatal 6-OHDA lesion of the SNc induces striatal compensatory sprouting from surviving SNc dopaminergic neurons without VTA contribution
Authors: Tanguay William , Ducrot Charles , Giguère Nicolas , Bourque Marie-Josée , Trudeau Louis-Eric 
Published: March 2021

AbstractDopamine (DA) neurons of thesubstantia nigra pars compacta(SNc) are uniquely vulnerable to neurodegeneration in Parkinson’s disease (PD). We hypothesize that their large axonal arbor is a key factor underlying their vulnerability, due to increased bioenergetic, proteostatic and oxidative stress. In keeping with this model, other DAergic populations with smaller axonal arbors are mostly spared during the course of PD and are more resistant to experimental lesions in animal models. Aiming to improve mouse PD models, we examined if neonatal partial SNc lesions could lead to adult mice with fewer SNc DA neurons that are endowed with larger axonal arbors because of compensatory mechanisms. We injected 6-hydroxydopamine (6-OHDA) unilaterally in the SNc at an early postnatal stage at a dose selected to induce loss of approximately 50% of SNc DA neurons. We find that at 10- and 90-days after the lesion, the axons of SNc DA neurons show massive compensatory sprouting, as revealed by the proportionally smaller decrease in tyrosine hydroxylase (TH) in the striatum compared to the loss of SNc DA neuron cell bodies. The extent and origin of this axonal sprouting was further investigated by AAV-mediated expression of eYFP in SNc or ventral tegmental area (VTA) DA neurons of adult mice. Our results reveal that SNc DA neurons have the capacity to substantially increase their axonal arbor size and suggest that mice designed to have reduced numbers of SNc DA neurons could potentially be used to develop better mouse models of PD, with elevated neuronal vulnerability.Graphical abstract textWe describe a technique to induce the loss of approximately 50% of SNc DA neurons in neonate mice using unilateral intranigral 6-OHDA (left panel).Compensatory axonal sprouting was observed in the striatum as early as 10 days following the lesion (at P15), with effects lasting until adulthood (P90).Conditional AAV-mediated expression of eYFP (green) reveals SNc DA neurons, projecting to the dorsal striatum (middle panel), and not VTA DA neurons, projecting to the ventral striatum (right panel), as the main source of compensatory axonal sprouting.Graphical abstract
On the predictability of postoperative complications for cancer patients: a Portuguese cohort study
Authors: Gonçalves Daniel , Henriques Rui , Lara Santos Lúcio , Costa Rafael S 
Published: March 2021

AbstractPostoperative complications following cancer surgeries are still hard to predict despite the historical efforts towards the creation of standard clinical risk scores. The differences among score calculators, contribute for the creation of highly specialized tools, with poor reusability in foreign contexts, resulting in larger prediction errors in clinical practice.This work aims to predict postoperative complications risk for cancer patients, offering two major contributions. First, to develop and evaluate a machine learning-based risk score, specific for the Portuguese population using a retrospective cohort of 847 cancer patients undergoing surgery between 2016 and 2018, predicting 4 outcomes of interest: i) existence of postoperative complications, ii) severity level of complications, iii) number of days in the Intermediate Care Unit (ICU), and iv) postoperative mortality within 1 year. An additional cohort of 137 cancer patients was used to validate the models. Second, to support the study with relevant findings and improve the interpretability of predictive models.In order to achieve these objectives, a robust methodology for the learning of risk predictors is proposed, offering new perspectives and insights into the clinical decision process. For postoperative complications the mean Receiver Operating Characteristic Curve (AUC) was 0.69, for complications’ severity mean AUC was 0.65, for the days in the ICU the Mean Absolute Error (MAE) was 1.07 days, and for one-year postoperative mortality the mean AUC was 0.74, calculated on the development cohort.In this study, risk predictive models which may help guide physicians at estimating cancer patient’s risk of developing surgical complications were developed. Additionally, a web-based decision support system is further provided to this end.
Comparative analysis of the unbinding pathways of antiviral drug Indinavir from HIV and HTLV1 proteases by Supervised Molecular Dynamics simulation
Authors: Sohraby Farzin , Aryapour Hassan 
Published: March 2021

AbstractDetermining the unbinding pathways of potential small molecule compounds from their target proteins is of great significance for designing efficacious treatment solutions. One of these potential compounds is the approved HIV-1 protease inhibitor, Indinavir, which has a weak effect on the HTLV-1 protease. In this work, by employing the SuMD method, we reconstructed the unbinding pathways of Indinavir from HIV and HTLV-1 proteases to compare and understand the mechanism of the unbinding and discover the reasons for the lack of inhibitory activity against the HTLV-1 protease. We achieved multiple unbinding events from both HIV and HTLV-1 proteases. Also, we found that the mobility and fluctuations of the flap region are higher in the HTLV-1 protease, making the drug less stable. We realized that critically positioned aromatic residues such as Trp98/Trp98′ and Phe67/Phe67′ in the HTLV-1 protease could make strong π-Stacking interactions with Indinavir, which are unfavorable for the stability of Indinavir in the active site. The details found in this study can make a reasonable explanation for the lack of inhibitory activity of this drug against HTLV-1 protease. We believe the details discovered in this work can help design more effective and more selective inhibitors for the HTLV-1 protease.
Generation and first characterization of TRDC-Knockout pigs lacking γδ T cells
Authors: Petersen Bjoern , Kammerer Robert , Frenzel Antje , Hassel Petra , Dau Tung Huy , Becker Roswitha , Breithaupt Angele , Ulrich Reiner Georg , Lucas-Hahn Andrea , Meyers Gregor 
Published: March 2021

AbstractThe TRDC-Locus encodes the T cell receptor delta constant region, one component of the γδ T cell receptor which is essential for development of γδ T cells. In contrast to peptide recognition by αβ T cells, antigens activating γδ T cells are mostly MHC independent and not well characterized. Therefore, the function of γδ T cells and their contribution to protection against infections is still unclear. Higher numbers of circulating γδ T cells compared to mice, render the pig a suitable animal model to study γδ T cells. Knocking-out the porcine TRDC-locus by intracytoplasmic microinjection and somatic cell nuclear transfer resulted in healthy living γδ T cell deficient offspring. Flow cytometric analysis revealed that TRDC-KO pigs lack γδ T cells in peripheral blood mononuclear cells (PBMC) and spleen cells. The composition of the remaining leucocyte subpopulations was not affected by the depletion of γδ T cells. Genome-wide transcriptome analyses in PBMC revealed a pattern of changes reflecting the impairment of known or expected γδ T cell dependent pathways. Histopathology did not reveal developmental abnormalities of secondary lymphoid tissues. However, in a vaccination experiment the KO pigs stayed healthy but had a significantly lower neutralizing antibody titer as the syngenic controls.
Desiccation stress acts as cause as well as cost of dispersal inDrosophila melanogaster
Authors: Mishra Abhishek , Tung Sudipta , Sruti V.R. Shree , Shreenidhi P.M. , Dey Sutirth 
Published: March 2021

AbstractEnvironmental stress is one of the important causes of biological dispersal. At the same time, the process of dispersal itself can incur and/or increase susceptibility to stress for the dispersing individuals. Therefore, in principle, stress can serve as both a cause and a cost of dispersal.Desiccation stress is an environmentally relevant stress faced by many organisms, known to shape their population dynamics and distribution. However, the potentially contrasting roles of desiccation stress as a cause and a cost of dispersal have not been investigated. Furthermore, while desiccation stress often affects organisms in a sex-biased manner, it is not known whether the desiccation-dispersal relationship varies between males and females.We studied the role of desiccation stress as a cause and cost of dispersal in a series of experiments usingD. melanogasteradults in two-patch dispersal setups. We were interested in knowing whether (a) dispersers are the individuals that are more susceptible to desiccation stress, (b) dispersers pay a cost in terms of reduced resistance to desiccation stress, (c) dispersal evolution alters the desiccation cost of dispersal, and (d) females pay a reproductive cost of dispersal. For this, we modulated the degree of desiccation stress faced by the flies as well as the provision of rest following a dispersal event.Our data showed that desiccation stress served as a significant cause of dispersal in both sexes. Further investigation revealed an increase in both male and female dispersal propensity with increasing desiccation duration. Next, we found a male-biased cost of dispersal in terms of reduced desiccation resistance. This trend was preserved in dispersal-selected and non-selected controls as well, where the desiccation cost of dispersal in females was very low compared to the males. Finally, we found that the females instead paid a significant reproductive cost of dispersal.Our results highlight the complex relationship between desiccation stress and dispersal, whereby desiccation resistance can show both a positive and a negative association with dispersal. Furthermore, the sex differences observed in these trait associations may translate into differences in movement patterns, thereby giving rise to sex-biased dispersal.