bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybrid systems modeling of ecological population dynamics
Authors: Singh Abhyudai , Emerick Brooks 
Published: March 2020

AbstractDiscrete-time models are the traditional approach for capturing population dynamics of insects living in the temperate regions of the world. These models are characterized by an update function that connects the population densities from one year to the next. We revisit classical discrete-time models used for modeling interactions between two insect species (a host and a parasitoid), and provide novel result on the stability of the population dynamics. In particular, for a class of models we show that the fixed point is stable, if and only if, the host equilibrium density is an increasing function of the host’s reproduction rate. We also introduce a hybrid approach for obtaining the update functions by solving ordinary differential equations that mechanistically capture the ecological interactions between the host and the parasitoid. This hybrid approach is used to study the suppression of host density by a parasitoid. Our analysis shows that when the parasitoid attacks the host at a constant rate, then the host density cannot by suppressed beyond a certain point without making the population dynamics unstable. In contrast, when the parasitoid’s attack rate increases with increasing host density, then the host population density can be suppressed to arbitrarily low levels. These results have important implications for biological control where a natural enemy, such as a parasitoid wasp, is introduced to eliminate a pest that is the host species for the parasitoid.
MORFEE: a new tool for detecting and annotating single nucleotide variants creating premature ATG codons from VCF files
Authors: Aïssi Dylan , Soukarieh Omar , Proust Carole , Jaspard-Vinassa Beatrice , Fautrad Pierre , Ibrahim-Kosta Manal , Leal-Valentim Felipe , Roux Maguelonne , Bacq-Daian Delphine , Olaso Robert , Deleuze Jean-François , Morange Pierre-Emmanuel , Trégouët David-Alexandre ,   on behalf of the GENMED Consortium
Published: March 2020

AbstractSummaryVariants in 5’UTR regions that create upstream translation initiation AUG codons are a class of neglected non coding variations. When they associate with a premature stop codon and create upstream open reading frames (uORFs) whose translation competes with that of natural proteins, they can have strong impact on human diseases. We here describe MORFEE, a new bioinformatics tool that detects, annotates and predicts, from a standard VCF file, the creation of uORF by any 5’UTR variants on uORF creation. MORFEE was applied to two genomic resources and identified candidate functional variants that could explain statistical association signals observed in the context of Genome Wide Association Studies or could be responsible for rare forms of diseases. In conclusion MORFEE is an easy-to-use tool complementary to existing ones that can help resolving genetic investigations that remained so far unfruitful.Availability and implementationMORFEE is written in R with code and package available athttps://github.com/daissi/MORFEE.Contactdavid-alexandre.tregouet@inserm.fr;david-alexandre.tregouet@u-bordeaux.fr
Suppression of cortico-striatal circuit activity improves cognitive flexibility and prevents body weight loss in activity-based anorexia in rats
Authors: Milton Laura K , Mirabella Paul N , Greaves Erika , Spanswick David C , van den Buuse Maarten , Oldfield Brian J , Foldi Claire J 
Published: March 2020

AbstractBackgroundThe ability to adapt behavior to changing environmental circumstances, orcognitive flexibility, is impaired in multiple psychiatric conditions, including anorexia nervosa (AN). Exaggerated prefrontal cortical activity likely underpins the inflexible thinking and rigid behaviors exhibited by patients with AN. A better understanding of the neural basis of cognitive flexibility is necessary to enable treatment approaches that may target impaired executive control.MethodsUtilizing the activity-based anorexia (ABA) rat model and touchscreen operant learning paradigms, we investigated the neurobiological link between pathological weight loss and cognitive flexibility. We used pathway-specific chemogenetics to selectively modulate activity in neurons of the medial prefrontal cortex (mPFC) projecting to the nucleus accumbens shell (AcbSh) in female Sprague-Dawley rats.ResultsDREADD-based inhibition of the mPFC-AcbSh pathway prevented weight loss in ABA and improved flexibility during early reversal learning by reducing perseverative responding. Modulation of activity within the mPFC-AcbSh pathway had no effect on running, locomotor activity or feeding under ad libitum conditions, indicating the specific involvement of this circuit in conditions of dysregulated reward.ConclusionsBoth attenuation of weight loss in ABA and improved cognitive flexibility following suppression of mPFC-AcbSh activity aligns with the relationship between disrupted prefrontal function and cognitive rigidity in AN patients. The identification of a neurobiological correlate between cognitive flexibility and pathological weight loss provides a unique insight into the executive control of feeding behavior. It also highlights the utility of the ABA model for understanding the biological bases of cognitive deficits in AN and provides context for new treatment strategies.
Prediction of Peak and Termination of Novel Coronavirus Covid-19 Epidemic in Iran
Authors: Zahiri Amir-Pouyan , RafieeNasab Sepehr , Roohi Ehsan 
Published: March 2020

AbstractThe growth and development of Covid-19 transmission have significantly cut the attention of many societies, particularly Iran that has been struggling with this contagious, infectious disease since late February 2020. In the present study, the known SIR model was used for the dynamics of an epidemic to provide a suitable assessment of the COVID-19 virus epidemic in Iran. The epidemic curve and SIR model parameters were obtained with the use of Iran statistical data. The recovered people were considered alongside the official number of confirmed victims as the reliable long-time statistical data of Iran. The results offered many important predictions of the COVID-19 virus epidemic such as realistic number of victims, infection rate, peak time, and other characteristics.
Rare variants in dynein heavy chain genes in two individuals withsitus inversusand developmental dyslexia
Authors: Bieder Andrea , Einarsdottir Elisabet , Matsson Hans , Nilsson Harriet E. , Eisfeldt Jesper , Dragomir Anca , Paucar Martin , Granberg Tobias , Li Tie-Qiang , Lindstrand Anna , Kere Juha , Tapia-Páez Isabel 
Published: March 2020

ABSTRACTBackgroundDevelopmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted left-right asymmetry of the brain may play a role in neurodevelopmental disorders such as DD.MethodsHere, we studied two individuals with co-occurringsitus inversus(SI) and DD using whole genome sequencing to identify single nucleotide variants or copy number variations of importance for DD and SI.ResultsIndividual 1 had primary ciliary dyskinesia (PCD), a rare, autosomal recessive disorder with oto-sino-pulmonary phenotype and SI. We identified two rare nonsynonymous variants in the dynein axonemal heavy chain 5 gene (DNAH5): c.7502G>C;p.(R2501P), a previously reported variant predicted to be damaging and c.12043T>G;p.(Y4015D), a novel variant predicted to be damaging. Ultrastructural analysis of the cilia revealed a lack of outer dynein arms and normal inner dynein arms. MRI of the brain revealed no significant abnormalities. Individual 2 had non-syndromic SI and DD. In individual 2, one rare variant (c.9110A>G;p.(H3037R)) in the dynein axonemal heavy chain 11 gene (DNAH11), coding for another component of the outer dynein arm, was identified.ConclusionsWe identified the likely genetic cause of SI and PCD in one individual, and a possibly significant heterozygosity in the other, both involving dynein genes. Given the present evidence, it is unclear if the identified variants also predispose to DD, but further studies into the association are warranted.
DrAFC: Drug Repositioning Through Anti-Fibrosis Characteristic
Authors: Wu Dingfeng , Gao Wenxing , Li Xiaoyi , Tian Chuan , Jiao Na , Fang Sa , Xiao Jing , Xu Zhifeng , Zhu Lixin , Zhang Guoqing , Zhu Ruixin 
Published: March 2020

AbstractFibrosis is a key component in the pathogenic mechanism of many diseases. These diseases involving fibrosis may share common mechanisms, therapeutic targets and therefore, common intervention strategies and medicines may be applicable for these diseases. For this reason, deliberately introducing anti-fibrosis characteristics into modelling may lead to more success in drug repositioning. In this study, anti-fibrosis knowledge base was first built by collecting data from multiple resources. Both structural and biological profiles were derived from the knowledge base and used for constructing machine learning models including Structural Profile Prediction Model (SPPM) and Biological Profile Prediction Model (BPPM). Three external public data sets were employed for validation purpose and further exploration of potential repositioning drugs in wider chemical space. The resulting SPPM and BPPM models achieve area under the receiver operating characteristic curve (AUC) of 0.879 and 0.972 in the training set, and 0.814 and 0.874 in the testing set. Additionally, our results also demonstrate that substantial amount of multi-targeting natural products possess notable anti-fibrosis characteristics and might serve as encouraging candidates in fibrosis treatment and drug repositioning. To leverage our methodology and findings, we developed repositioning prediction platform, Drug Repositioning based on Anti-Fibrosis Characteristic (DrAFC) that is freely accessible viahttps://www.biosino.org/drafc.
A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation
Authors: Yao Zizhen , Nguyen Thuc Nghi , van Velthoven Cindy T. J. , Goldy Jeff , Sedeno-Cortes Adriana E. , Baftizadeh Fahimeh , Bertagnolli Darren , Casper Tamara , Crichton Kirsten , Ding Song-Lin , Fong Olivia , Garren Emma , Glandon Alexandra , Gray James , Graybuck Lucas T. , Hirschstein Daniel , Kroll Matthew , Lathia Kanan , Levi Boaz , McMillen Delissa , Mok Stephanie , Pham Thanh , Ren Qingzhong , Rimorin Christine , Shapovalova Nadiya , Sulc Josef , Sunkin Susan M. , Tieu Michael , Torkelson Amy , Tung Herman , Ward Katelyn , Dee Nick , Smith Kimberly A. , Tasic Bosiljka , Zeng Hongkui 
Published: March 2020

SUMMARYThe isocortex and hippocampal formation are two major structures in the mammalian brain that play critical roles in perception, cognition, emotion and learning. Both structures contain multiple regions, for many of which the cellular composition is still poorly understood. In this study, we used two complementary single-cell RNA-sequencing approaches, SMART-Seq and 10x, to profile ∼1.2 million cells covering all regions in the adult mouse isocortex and hippocampal formation, and derived a cell type taxonomy comprising 379 transcriptomic types. The completeness of coverage enabled us to define gene expression variations across the entire spatial landscape without significant gaps. We found that cell types are organized in a hierarchical manner and exhibit varying degrees of discrete or continuous relatedness with each other. Such molecular relationships correlate strongly with the spatial distribution patterns of the cell types, which can be region-specific, or shared across multiple regions, or part of one or more gradients along with other cell types. Glutamatergic neuron types have much greater diversity than GABAergic neuron types, both molecularly and spatially, and they define regional identities as well as inter-region relationships. For example, we found that glutamatergic cell types between the isocortex and hippocampal formation are highly distinct from each other yet possess shared molecular signatures and corresponding layer specificities, indicating their homologous relationships. Overall, our study establishes a molecular architecture of the mammalian isocortex and hippocampal formation for the first time, and begins to shed light on its underlying relationship with the development, evolution, connectivity and function of these two brain structures.
Essential roles of plexin-B3+oligodendrocyte precursor cells in the pathogenesis of Alzheimer’s disease
Authors: Nihonmatsu-Kikuchi Naomi , Yu Xiu-Jun , Matsuda Yoshiki , Ozawa Nobuyuki , Ito Taeko , Satou Kazuhito , Kaname Tadashi , Takashima Akihiko , Toru Shuta , Hirokawa Katsuiku , Hasegawa Masato , Uchihara Toshiki , Tatebayashi Yoshitaka 
Published: March 2020

AbstractThe roles played by oligodendrocyte (OL) lineage cells, the largest glial population in the adult CNS, in the pathogenesis of Alzheimer’s disease (AD) remain elusive. Here, we show a newly developed culture method for adult OL progenitor cells (aOPCs) and identify novel plexin-B3-expressing (plexin-B3+) aOPCs as potential amyloid β peptides (Aβ)-secreting cells. Fibroblast growth factor 2 (FGF2) promotes the survival and proliferation of aOPCs in a serum-free defined medium. Although the whole expression profiles of the expanded aOPCs closely resemble those of in vivo OPCs, we found a subpopulation (up to 5%) of plexin-B3+/olig2+aOPCs in the cultures growing in FGF2. FGF2 withdrawal decreased NG2+, but increased plexin-B3+aOPCs with increased APP expression, Aβ1-40, −42 secretions and Aβ1-42/total Aβ ratios in association with cored senile plaque-like morphological changes. In vivo, plexin-B3+aOPCs are distributed throughout the adult brain, although less densely so than NG2+aOPCs. Spreading depolarization, a type of brain injury, induced unique delayed cortical plexin-B3+aOPC gliosis in the ipsilateral, but not in the contralateral, remote cortex. In AD brains, virtually all senile plaques in the cortex were immunostained with plexin-B3 antibodies and the levels of cortical plexin-B3 expression increased significantly in the Salcosyl-soluble fractions. These findings suggest that plexin-B3+aOPCs play important roles in the pathogenesis of AD most likely as a natural Aβ source.
Characterization of dynamic age-dependent changes and driver microbes in primate gut microbiota during host’s development and healthy aging via captive crab-eating macaque model
Authors: Wei Zhi-Yuan , Rao Jun-Hua , Tang Ming-Tian , Zhao Guo-An , Li Qi-Chun , Wu Li-Ming , Liu Shao-Qiang , Li Bi-Hai , Xiao Bai-Quan , Liu Xing-Yin , Chen Jian-Huan 
Published: March 2020

AbstractRecent population studies have significantly advanced our understanding of how age shapes the gut microbiota. However, the actual role of age could be inevitably confounded due to varying environmental factors in human populations. A well-controlled environment is thus necessary to reduce undesirable cofounding effects, and recapitulate age-dependent taxonomic and functional changes in the healthy primate gut microbiota. Herein we performed 16S rRNA gene sequencing, characterized age-associated gut microbial profiles from infant to elderly crab-eating macaques reared in captivity, and systemically revealed lifelong dynamic changes of primate gut microbiota in the model. While the most significantly age-associated gut microbial taxa were mainly found in commensals such asFaecalibacterium, a set of suspicious pathogens such asHelicobacterwere exclusively enriched in infants, pointing to their potential role in host development. Importantly, topology analysis indicated that the connectivity of gut microbial network was even more age-dependent than taxonomic diversity, with its tremendous decline probably linked to the host’s healthy aging. NetShift analysis identifiedPrevotella 9, Rikenellaceae RC9 gut groupandMegasphaeraas key drivers during gut microbiota maturation and development, actively involved in age-dependent changes in phenotypes and functions of the gut microbial community. The current study demonstrates lifelong age-dependent changes in healthy primate gut microbiota. Our findings indicate potential importance of appropriate exposure to suspicious pathogens in infant development. The age-associated baseline profiles and driver microbes of primate gut microbiota in the current study could provide new insight into its role in the host’s development and healthy aging.
Eye movements modulate neural activity in the human anterior thalamus during visual active sensing
Authors: Leszczynski Marcin , Staudigl Tobias , Chaieb Leila , Enkirch Simon Jonas , Fell Juergen , Schroeder Charles E. 
Published: March 2020

AbstractHumans and other primates explore visual scenes byactive sensing, using saccadic eye movements to relocate the fovea and sample different bits of information multiple times per second. Saccades induce a phase reset of ongoing neuronal oscillations in primary and higher-order visual cortices and medial temporal lobe. As a result, neuron ensembles are shifted to a common state at the time visual input propagates through the system (i.e., just after fixation). The extent of the brain’s circuitry modulated by saccades is not yet known. Here, we evaluate the possibility that saccadic phase reset impacts the anterior nuclei of the thalamus (ANT). Using rare recordings in the human thalamus of three surgical patients, we found saccade-related phase concentration, peaking at 3-4 Hz, coincident with suppression of Broadband High-frequency Activity (BHA; 80-180 Hz). Our results provide evidence for saccade-related modulation of neuronal excitability dynamics in the ANT, consistent with the idea that these nuclei are engaged during visual active sensing. These findings show that during real-world active visual exploration neural dynamics in the human ANT, a part of extended hippocampal–diencephalic system for episodic memory, exhibit modulations that might be underestimated in typical passive viewing.
Coordinate genomic association of transcription factors controlled by an imported quorum sensing peptide inCryptococcus neoformans
Authors: Summers Diana K. , Perry Daniela S. , Rao Beiduo , Madhani Hiten D. 
Published: March 2020

ABSTRACTQsp1 is a secreted quorum sensing peptide required for virulence of the fungal meningitis pathogenCryptococcus neoformans.Qsp1 functions to control cell wall integrity in vegetatively growing cells and also functions in mating. Rather than acting on a cell surface receptor, Qsp1 is imported to act intracellularly via the predicted oligopeptide transporter Opt1. Here, we identify a transcription factor network as a target of Qsp1. Using whole-genome chromatin immunoprecipitation, we find Qsp1 controls the genomic associations of three transcription factors to genes whose outputs are regulated by Qsp1. One of these transcription factors, Cqs2, is also required for the action of Qsp1 during mating, indicating that it might be a shared proximal target of Qsp1. Consistent with this hypothesis, deletion ofCQS2impacts the binding of other network transcription factors specifically to Qsp1-regulated genes. These genetic and genomic studies illuminate mechanisms by which an imported peptide acts to modulate eukaryotic gene expression.AUTHOR SUMMARYFor many fungal pathogens, the ability to adapt to changing and diverse environments forms the basis for their ability to infect and survive inside macrophages and other niches in the human body, and these changes are accomplished by transcription factors. Many pathogenic microbes coordinate their gene expression as a function of cell density in a process known as quorum sensing. Here, in the human fungal meningitis pathogenCryptococcusneoformans, we find that an imported eukaryotic quorum sensing peptide that is important for virulence, Qsp1, controls the binding of three different transcription factors to promoters, thereby modulating the expression of Qsp1-regulated genes. This discovery reveals the mechanism for how an imported peptide affects gene expression.
A Flexible, Interpretable, and Accurate Approach for Imputing the Expression of Unmeasured Genes
Authors: Mancuso Christopher A , Canfield Jacob L , Singla Deepak , Krishnan Arjun 
Published: March 2020

AbstractWhile there are >2 million publicly-available human microarray gene-expression profiles, these profiles were measured using a variety of platforms that each cover a pre-defined, limited set of genes. Therefore, key to reanalyzing and integrating this massive data collection are methods that can computationally reconstitute the complete transcriptome in partially-measured microarray samples by imputing the expression of unmeasured genes. Current state-of-the-art imputation methods are tailored to samples from a specific platform and rely on gene-gene relationships regardless of the biological context of the target sample. We show that sparse regression models that capture sample-sample relationships (termedSampleLASSO), built on-the-fly for each new target sample to be imputed, outperform models based on fixed gene relationships. Extensive evaluation involving three machine learning algorithms (LASSO, k-nearest-neighbors, and deep-neural-networks), two gene subsets (GPL96-570 and LINCS), and three imputation tasks (within and across microarray/RNA-seq) establishes thatSampleLASSOis the most accurate model. Additionally, we demonstrate the biological interpretability of this method by showing that, for imputing a target sample from a certain tissue,SampleLASSOautomatically leverages training samples from the same tissue. Thus,SampleLASSOis a simple, yet powerful and flexible approach for harmonizing large-scale gene-expression data.
A forward genetic approach to mapping aP-element second site mutation identifiesDCP2as a novel tumor suppressor inDrosophila melanogaster
Authors: Kunar Rohit , Mishra Rakesh , Mandal Lolitika , Alone Debasmita P. , Chandrasekharan Shanti , Roy Jagat Kumar 
Published: March 2020

AbstractThe use of transposons to create mutants has been the cornerstone ofDrosophilagenetics in the past few decades. Transpositions often create second-site mutations, devoid of transposon insertion and thereby affect subsequent phenotype analyses. In aP-element mutagenesis screen, a second site mutant was discovered on chromosome 3 wherein the homozygous mutant individuals show the classic hallmarks of mutations in tumor suppressor genes including brain tumour and lethality, hence the mutant line was initially named aslethal (3) tumorous brain[l(3)tb]. Classical genetic approaches relying on meiotic recombination and subsequent complementation with chromosomal deletions and gene mutations mapped the mutation to CG6169, the mRNA decapping protein 2 (DCP2), on the left arm of the third chromosome (3L), and thus the mutation was renamed asDCP2l(3)tb. Fine mapping of the mutation further identified the presence of aGypsy-LTR like sequence in the 5’UTR coding region ofDCP2, alongwith expansion of the adjacent upstream intergenic AT-rich sequence. The mutant phenotypes are rescued by Introduction of a functional copy ofDCP2in the mutant background, thereby establishing the causal role of the mutation and providing a genetic validation of the allelism. With the increasing repertoire of genes being associated with tumor biology this is the first instance that the mRNA decapping protein is being implicated inDrosophilatumourigenesis. Our findings therefore imply a plausible role for mRNA degradation pathway in tumorigenesis and identifyDCP2as a potential candidate for future explorations of cell cycle regulatory mechanisms.