bluuebunny/crossref_metadata_2025_split huggingface dataset:
A deep learning model for analyzing noisy biological systems
Authors: Wang Shangying , Capponi Sara , Bianco Simone 
Published: October 2021

AbstractBiological systems are inherently noisy so that two genetically identical cells in the exact same environment will sometimes behave in dramatically different ways. This imposes a big challenge in building traditional supervised machine learning models that can only predict determined phenotypic variables or categories per specific input condition. Furthermore, biological noise has been proven to play a crucial role in gene regulation mechanisms. The prediction of the average value of a given phenotype is not always sufficient to fully characterize a given biological system. In this study, we develop a deep learning algorithm that can predict the conditional probability distribution of a phenotype of interest with a small number of observations per input condition. The key innovation of this study is that the deep neural network automatically generates the probability distributions based on only few (10 or less) noisy measurements for each input condition, with no prior knowledge or assumption of the probability distributions. This is extremely useful for exploring unknown biological systems with limited measurements for each input condition, which is linked not only to a better quantitative understanding of biological systems, but also to the design of new ones, as it is in the case of synthetic biology and cellular engineering.
Genome-scale modeling specifies the metabolic capabilities of Rhizophagus irregularis
Authors: Wendering Philipp , Nikoloski Zoran 
Published: October 2021

AbstractRhizophagus irregularis is one of the most extensively studied arbuscular mycorrhizal fungi (AMF) that forms symbioses with and improves the performance of many crops. Lack of transformation protocol for R. irregularis renders it challenging to investigate molecular mechanisms that shape the physiology and interactions of this AMF with plants. Here we used all published genomics, transcriptomics, and metabolomics resources to gain insights in the metabolic functionalities of R. irregularis by reconstructing its high-quality genome-scale metabolic network that considers enzyme constraints. Extensive validation tests with the enzyme-constrained metabolic model demonstrated that it can be used to: (1) accurately predict increased growth of R. irregularis on myristate with minimal medium; (2) integrate enzyme abundances and carbon source concentrations that yield growth predictions with high and significant Spearman correlation (ρS = 0.74) to measured hyphal dry weight; and (3) simulated growth rate increases with tighter association of this AMF with the host plant across three fungal structures. Based on the validated model and system-level analyses that integrate data from transcriptomics studies, we predicted that differences in flux distributions between intraradical mycelium and arbuscles are linked to changes in amino acid and cofactor biosynthesis. Therefore, our results demonstrated that the enzyme-constrained metabolic model can be employed to pinpoint mechanisms driving developmental and physiological responses of R. irregularis to different environmental cues. In conclusion, this model can serve as a template for other AMF and paves the way to identify metabolic engineering strategies to modulate fungal metabolic traits that directly affect plant performance.ImportanceMounting evidence points at the benefits of the symbiotic interactions between the arbuscular mycorrhiza fungus Rhizophagus irregularis and crops; yet, the molecular mechanisms underlying the physiological responses of this fungus to different host plants and environments remain largely unknown. We present a manually curated, enzyme-constrained genome-scale metabolic model of R. irregularis that can accurately predict experimentally observed phenotypes. We show that this high-quality model provides an entry point into better understanding the metabolic and physiological responses of this fungus to changing environments due to the availability of different nutrients. The model can be used to design metabolic engineering strategies to tailor R. irregularis metabolism towards improving the performance of host plants.
COVID-19 Pandemic Impact on Sexually Transmitted Infection Testing in a College Setting
Authors: Marconi Agustina , Falk-Hanson Elizabeth C , Crass Megan , Campbell Peter 
Published: October 2021

AbstractObjectiveAssess the impact of the pandemic on STI (sexually transmitted infections) testing in a college health setting.DesignExploratory analysis of the number of STI tests done, positive rates for those tests and of percentage of “compliance to follow-up” from March to December 2020 and its comparison with historical data at the University Health Services, UW-Madison.Samplestudents’ STI tests during the analyzed period.MeasurementObserved (2020) vs Expected (2015-2019, average) number of STI tests, positive rate, compliance to follow-up testing for STIs.ResultsThere was a significant decrease in the number of tests done and increase of positive rate when compared to historical for total sample and per sex. There was a decrease in the percentage of follow-up for the entire sample and females and an increase for males.ConclusionsConsidering the three outcomes assessed, we observe an impact in STI testing during the pandemic. In concordance with national data, our analysis shows significant declines in STI testing and follow-up during 2020 compared to previous years and an increase in positivity rate. The finding of higher positivity with lower number of tests is likely due to triaging patients, facilitating testing for those at highest risk of infection.
Is Human Bocavirus Infection Associated with Gastroenteritis in Children? An Updated Systematic Review and Meta-analysis
Authors: Zhang Minyi , Liang Minyi , Li Qiushuang , Xian Juxian , Wu Fei , Zheng Liting , Chen Qing 
Published: October 2021

AbstractBackgroundHuman bocavirus (HBoV) figures as an increased risk factor of respiratory and gastrointestinal tract infections among children. A great deal of data is available to support the pathogenic role of HBoV in acute respiratory diseases. However, the association between HBoV infection and gastroenteritis remains controversial due to the ambiguous results. The present work aims to clarify the role of HBoV as a cause of gastroenteritis in children.Methodology/Principal findingsA systematic search of the literature was carried out from 1 January 2016 to 29 August 2021 in Embase, PubMed, Scopus, Web of Science, and the Chinese bibliographic database of biomedicine (CBM). Data from included studies were analyzed by use of a random-effects model. The pooled estimates of HBoV prevalence among all cases of gastroenteritis were generated and stratified by potential confounders. The pooled odds ratio (OR) and 95% confidence interval (CI) were computed for HBoV infection in relation to the risk of gastroenteritis. The overall prevalence of HBoV in children with gastroenteritis (9.1%, 95% CI: 6.7-11.8%) was considerably higher than that detected in children without gastroenteritis (4.0%, 95% CI: 1.1-8.5%). HBoV prevalence tended to be higher in cases of gastroenteritis under five years of age (12.1%, 95% CI: 6.8-18.7%). The highest frequency of HBoV was found in Egypt (57.8%, 95% CI: 47.7-67.6%). The predominant genotypes of HBoV circulating in children with gastroenteritis were genotype 1 (HBoV1, 3.8%, 95% CI: 2.7-5.2%) and genotype 2 (HBoV2, 2.4%, 95% CI: 1.3-3.7%). HBoV infection was significantly associated with an increased risk of gastroenteritis in children (OR 1.620, 95% CI: 1.023-2.566).ConclusionThe HBoV prevalence in pediatric cases of gastroenteritis is higher than that in children without gastroenteritis, demonstrating an increasing global burden of gastroenteritis in children caused by HBoV infection. Targeted intervention to reduce the HBoV burden should be established.Author summaryIn addition to the known gastroenteritis-associated pathogens (rotavirus and norovirus et al.), several novel viruses that might be caused agents of diarrhea have been gradually determined, such as HBoV. The impact of HBoV infection on the development of childhood gastroenteritis remains ambiguous and in need of verifications. This work clarifies the association between HBoV infection and the risk of gastroenteritis in children based on the review literature. The estimated HBoV prevalence in all cases of gastroenteritis was categorized into different subgroups following the potential confounders, including age, gender, country, and HBoV genotypes. The main finding of this work was the significant association between HBoV infection and the development of childhood gastroenteritis. Our systematic review highlighted that HBoV infection contributes to the increased global burden of gastroenteritis in children.
Tracking Action in XR Mark Test Reveals Developing Body Representation Among Toddlers
Authors: Miyazaki Michiko , Asai Tomohisa , Ban Norihiro , Mugitani Ryoko 
Published: October 2021

AbstractDespite its popularity as an index of self-recognition, the mark test has not been used for assessing representations of the bodily self. This study combines the mark test and cross-reality task, to demonstrate novel aspects of children’s body representation and its development. Participants’ real-time skeletal data was captured, and virtual marks were displayed on 30 body parts for participants to interact through touch. The accuracy and trajectory of the first touch and reaction time were analyzed. Thirty Japanese 2- and 3-year-olds participated. Localization error could be predicted by dynamical body part coordination. Three-year-olds displayed fast and predictive reaching instead of visually guided reaching. Analyzing hand-reaching strategies in the XR mark test revealed aspects of the development of sensorimotor body representations.
EXTRA LARGE G-PROTEIN 2 (XLG2) mediates cell death and hyperimmunity via a novel, apoplastic ROS-independent pathway inArabidopsis thaliana
Authors: Petutschnig Elena , Anders Julia , Stolze Marnie , Meusel Christopher , Hacke Ronja , Schwier Melina , Gippert Anna-Lena , Kroll Samuel , Fasshauer Patrick , Wiermer Marcel , Lipka Volker 
Published: October 2021

ABSTRACTHeterotrimeric G-Proteins are signal transduction complexes comprised of three subunits, Gα, Gβ and Gγ, and are involved in many aspects of plant life. The non-canonical Gα subunit XLG2 mediates PAMP-induced ROS generation and immunity downstream of PRRs. A mutant of the chitin receptor component CERK1,cerk1-4, maintains normal chitin signalling capacity, but shows excessive cell death upon infection with powdery mildews. We identifiedXLG2mutants as suppressors of thecerk1-4 phenotype.We generated stably transformedArabidopsislines expressing Venus-XLG2 and numerous mutated variants. These were analysed by confocal microscopy, Western blotting and pathogen infection. We also crossedcerk1-4 with several mutants involved in immunity and analysed their phenotype. Phosphorylation of XLG2 was investigated by quantitative proteomics.Mutations in XLG2 complex partners AGB1 and AGG1 have a partialcerk1-4 suppressor effect. Thecerk1-4 phenotype is independent of NADPH oxidase-generated ROS, BAK1 and SOBIR1, but requires PUB2. XLG2 mediatescerk1-4 cell death at the cell periphery. Integrity of the XLG2 N-terminal domain, but not its phosphorylation, is essential for correct XLG2 localisation andcerk1-4 signalling.Our results suggest that XLG2 transduces signals from an unknown cell surface receptor that activates an apoplastic ROS-independent cell death pathway inArabidopsis.
Robustness in regulatory networks of Epithelial Mesenchymal Plasticity as a function of positive and negative feedback loops
Authors: Hebbar Anish , Moger Ankush , Hari Kishore , Jolly Mohit Kumar 
Published: October 2021

AbstractEpithelial-Mesenchymal plasticity (EMP) is a key arm of cancer metastasis and is observed across many contexts. Cells undergoing EMP can reversibly switch between three classes of phenotypes: Epithelial (E), Mesenchymal (M), and Hybrid E/M. While a large number of multistable regulatory networks have been identified to be driving EMP in various contexts, the exact mechanisms and design principles that enable robustness in driving EMP across contexts are not yet fully understood. Here we investigated dynamic and structural robustness in EMP networks with regards to phenotypic distribution and plasticity. We use two different approaches to simulate these networks: a computationally inexpensive, parameter-independent continuous state space boolean model, and an ODE-based parameter-agnostic framework (RACIPE), both of which yield similar phenotypic distributions. Using perturbations to network topology and by varying network parameters, we show that multistable EMP networks are structurally and dynamically more robust as compared to their randomized counterparts, thereby highlighting their topological hallmarks. These features of robustness are governed by a balance of positive and negative feedback loops embedded in these networks. Using a combination of the number of negative and positive feedback loops weighted by their lengths and sign, we identified a metric that can explain the structural and dynamical robustness of these networks. This metric enabled us to compare networks across multiple sizes, and the network principles thus obtained can be used to identify fragilities in large networks without simulating their dynamics. Our analysis highlights a network topology-based approach to quantify robustness in multistable EMP networks.Significance StatementEpithelial-Mesenchymal plasticity (EMP) is a key arm of cancer metastasis. Despite extensive intra- and inter-tumor heterogeneity, the characteristics of EMP have been observed to be robust across multiple contexts. We hypothesize that topology of EMP regulatory networks contributes towards this robustness. Here, we measure the robustness of EMP in the form of its phenotypic heterogeneity and multistability and show that EMP networks are more robust to dynamical (change in kinetic parameters) and structural (change in network topology) perturbations as compared to their random network counterparts. Furthermore, we propose a network topology-based metric using the nature and length of feedback loops that explains the observed robustness. Our metric hence serves to quantify robustness in multistable EMP networks without simulating their dynamics.
Light-induced asymmetries in the embryonic retina are mediated by the vascular system and extracellular matrix
Authors: Versace Elisabetta , Sgadò Paola , George Julia , Loveland Jasmine L. , Ward Joseph , Thorpe Peter , Jensen Lars Juhl , Spencer Karen A. , Paracchini Silvia , Vallortigara Giorgio 
Published: October 2021

AbstractLeft-right asymmetries in the nervous system (lateralisation) influence a broad range of behaviours, from social responses to navigation and language. The role and pathways of endogenous and environmental mechanisms in the ontogeny of lateralisation remains to be established. The domestic chick is a model of both endogenous and experience-induced lateralisation driven by light exposure. Following the endogenous rightward rotation of the embryo, the asymmetrical position in the egg results in a greater exposure of the right eye to environmental light. To identify the genetic pathways activated by asymmetric light stimulation, and their time course, we exposed embryos to different light regimes: darkness, 6 hours of light and 24 hours of light. We used RNA-seq to compare gene expression in the right and left retinas and telencephalon. As expected, no differential expression between left and right was present in darkness. We detected differential gene expression in right vs left retina after 6 hours of light exposure. This difference disappeared before 24 hours of light exposure, suggesting that light-induced activation is a self-terminating phenomenon. This transient effect of light exposure was associated with a downregulation of the sensitive-period mediator gene DIO2 (iodothyronine deiodinase 2) in the right retina. No differences between genes expressed in the right vs. left telencephalon were detected. Gene networks associated with lateralisation were connected to vascularisation, cell motility, and the extracellular matrix. Interestingly, we know that the extracellular matrix– including the differentially expressed PDGFRB (platelet-derived growth factor receptor β) gene – is involved in both sensitive periods and in the endogenous chiral mechanism of primary cilia, that drives lateralisation. Our data show a similarity between endogenous and experience-driven lateralisation, identifying functional gene networks that affect lateralisation in a specific time window.
On the relation between input and output distributions of scRNA-seq experiments
Authors: Schwabe Daniel , Falcke Martin 
Published: October 2021

Structured AbstractMotivationSingle-cell RNA sequencing determines RNA copy numbers per cell for a given gene. However, technical noise poses the question how observed distributions (output) are connected to their cellular distributions (input).ResultsWe model a single-cell RNA sequencing setup consisting of PCR amplification and sequencing, and derive probability distribution functions for the output distribution given an input distribution. We provide copy number distributions arising from single transcripts during PCR amplification with exact expressions for mean and variance. We prove that the coefficient of variation of the output of sequencing is always larger than that of the input distribution. Experimental data reveals the variance and mean of the input distribution to obey characteristic relations, which we specifically determine for a HeLa data set. We can calculate as many moments of the input distribution as are known of the output distribution (up to all). This, in principle, completely determines the input from the output distribution.Contactmartin.falcke@mdc-berlin.de
Proximity interactome of LC3B in normal growth conditions
Authors: Nollet Marie , Agrotis Alexander , Michailidis Fanourios , Dokal Arran David , Rajeeve Vinothini , Burden Jemima , Nightingale Thomas D. , Cutillas Pedro , Ketteler Robin , Kermorgant Stéphanie 
Published: October 2021

AbstractLC3 (Light Chain 3) is a key player of autophagy, a major stress-responsive proteolysis pathway promoting cellular homeostasis. It coordinates the formation and maturation of autophagosomes and recruits cargo to be further degraded upon autophagosome-lysosome fusion. To orchestrate its functions, LC3 binds to multiple proteins from the autophagosomes’ inner and outer membranes, but the full extent of these interactions is not known. Moreover, LC3 has been increasingly reported in other cellular locations than the autophagosome, with cellular outcome not fully understood and not all related to autophagy. Furthermore, novel functions of LC3 as well as autophagy can occur in cells growing in a normal medium thus in non-stressed conditions. A better knowledge of the molecule in proximity to LC3 in normal growth conditions will improve the understanding of LC3 function in autophagy and in other cell biology function. Using an APEX2 based proteomic approach, we have detected 407 proteins in proximity to the well-characterised LC3B isoform in non-stress conditions. These include known and novel LC3B proximity proteins, associated with various cell localisation and biological functions. Sixty-nine of these proteins contain a putative LIR (LC3 Interacting Region) including 41 not reported associated to autophagy. Several APEX2 hits were validated by co-immunoprecipitation and co-immunofluorescence. This study uncovers the LC3B global interactome and reveals novel LC3B interactors, irrespective of LC3B localisation and function. This knowledge could be exploited to better understand the role of LC3B in autophagy and non-autophagy cellular processes.
Disrupted intrinsic connectivity links to language and social deficits in toddlers with autism
Authors: Xiao Yaqiong , Wen Teresa H. , Kupis Lauren , Eyler Lisa T. , Goel Disha , Lombardo Michael V. , Pierce Karen , Courchesne Eric 
Published: October 2021

AbstractSocial and language abilities are closely intertwined during early development. Yet, it is still unknown how neural features underlying early social and language deficits are linked in toddlers with autism spectrum disorders (ASD). We examined functional connectivity of left and right temporal language regions and its correlations with language and social abilities in a cohort of 1– 4 years old toddlers (52 ASD/34 non-ASD). Further, ASD toddlers were stratified into those who strongly prefer social visual stimuli (ASDSoc) vs. those who do not (ASDnonSoc) based on performance on an eye-tracking paradigm. In non-ASD toddlers, connectivity between temporal regions and other language- and social-related cortical regions was significantly correlated with language, communication, and social scores. Conversely, ASD toddlers showed atypical correlations between temporal–visual cortex (cuneus) connectivity and communication ability. This temporal–visual connectivity was also correlated with social visual attention in ASDnonSocbut not in ASDSoctoddlers. These findings suggest language- and social-related functional connectivity was not correlated with language and social functions in ASD toddlers. Abnormal engagement of temporal–visual cortex connectivity may be an early-age signature of ASD and may help explain why interventions targeting social skills and language are so challenging, particularly in those with poor social engagement.
Population-scale long-read sequencing uncovers transposable elements contributing to gene expression variation and associated with adaptive signatures inDrosophila melanogaster
Authors: Rech Gabriel E. , Radío Santiago , Guirao-Rico Sara , Aguilera Laura , Horvath Vivien , Green Llewellyn , Lindstadt Hannah , Jamilloux Véronique , Quesneville Hadi , González Josefa 
Published: October 2021

ABSTRACTHigh quality reference genomes are crucial to understanding genome function, structure and evolution. The availability of reference genomes has allowed us to start inferring the role of genetic variation in biology, disease, and biodiversity conservation. However, analyses across organisms demonstrate that a single reference genome is not enough to capture the global genetic diversity present in populations. In this work, we generated 32 high-quality reference genomes for the well-known model speciesD. melanogasterand focused on the identification and analysis of transposable element variation as they are the most common type of structural variant. We showed that integrating the genetic variation across natural populations from five climatic regions increases the number of detected insertions by 58%. Moreover, 26% to 57% of the insertions identified using long-reads were missed by short-reads methods. We also identified hundreds of transposable elements associated with gene expression variation and new TE variants likely to contribute to adaptive evolution in this species. Our results highlight the importance of incorporating the genetic variation present in natural populations to genomic studies, which is essential if we are to understand how genomes function and evolve.