bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutive depletion of brain serotonin differentially affects rats’ social and cognitive abilities
Authors: Alonso Lucille , Peeva Polina , Stasko Sabrina , Bader Michael , Alenina Natalia , Winter York , Rivalan Marion 
Published: September 2021

AbstractBackgroundCentral serotonin is an essential neuromodulator for mental disorders. It appears a promising transdiagnostic marker of distinct psychiatric disorders and a common modulator of some of their key behavioral symptoms. We aimed to identify the behavioral markers of serotonergic function in rats and compare them to human deficits.MethodsWe applied a comprehensive profiling approach in adult maleTph2−/−rats constitutively lacking central serotonin. Under classical and ethological testing conditions, we tested each individual’s cognitive, social and non-social abilities and characterized the group organization (i.e. social network, hierarchy). Using unsupervised machine learning, we identified the functions most dependent on central serotonin.ResultsIn classical procedures,Tph2−/−rats presented an unexpected normal cognitive profile. Under the complex and experimenter-free conditions of their home-cage, the sameTph2−/−rats presented drastic changes in their daily life. Brain serotonin depletion induced compulsive aggression and sexual behavior, hyperactive and hypervigilant stereotyped behavior, reduced self-care and body weight, and exacerbated corticosterone levels. Group-housedTph2−/−rats showed strong social disorganization with disrupted social networks and hierarchical structure, which may arise from communication deficits and cognitive blunting.ConclusionsSerotonin depletion induced a profile reminiscent of the symptomatology of impulse control and anxiety disorders. Serotonin was necessary for behavioral adaptation to dynamic social environments. In classical testing conditions, our animal model challenged the concept of an essential role of serotonin in decision-making, flexibility, and impulsivity, although developmental compensations may have occurred. These contrasting findings highlight the need to generalize the evaluation of animal models’ multidimensional functions within the complexity of the social living environment.
Protein sequence profile prediction using ProtAlbert transformer
Authors: Behjati Armin , Zare-Mirakabad Fatemeh , Arab Seyed Shahriar , Nowzari-Dalini Abbas 
Published: September 2021

AbstractProtein profiles have many applications in bioinformatics. To construct the profile from a protein sequence, the sequence is aligned with database. However, sometimes there are no similar sequences with the query. This paper proposes a method based on pre-trained ProtAlbert transformer to predict the profile for a single protein sequence without alignment. The performance of transformers on natural languages is impressive. Protein sequences can be viewed as a language; therefore, we can benefit from using these models. We analyze the attention heads in different layers of ProtAlbert to show that the transformer can capture five essential protein characteristics of the family from a single protein sequence. These assessments are performed on the CASP13 dataset to find representative heads for each of five protein characteristics. Then, these heads are investigated on one thermophilic and two mesophilic proteins as case studies. The results show the significant attention heads for protein family properties extracted from a single protein sequence. This analysis led us to propose an algorithm called PA_SPP for profile prediction using only a single protein sequence as input. In our algorithm, we apply the masked language modeling method of ProtAlbert. The results display high similarity between the predicted profiles and HSSP profiles.
Genetic behavior analysis for phytochemical traits in coriander: Heterosis, inbreeding depression and genetic effects
Authors: Gholizadeh Amir , Khodadadi Mostafa 
Published: September 2021

AbstractIncreasing fruit yield, fatty acids and essential oils content in coriander are the main objectives. Reaching them need to understand the nature of gene action and quantifying the heterosis and inbreeding depression. Six genetically diverse parents, their 15 F1 one-way hybrids and 15 F2 populations were evaluated under different levels of water treatments. Beside the water treatment and genotype effects, the genetic effects of general (GCA) and specific (SCA) combining ability and their interactions with water treatment were significant for all traits. Water deficit stress decreased all traits in both F1 and F2 generations except for essential oil content which were significantly increased due to water deficit stress. Under water deficit stress, a non-additive gene action nature was predominant in F1 generation while an additive gene action nature was more important in F2 generation for all the traits except fruit yield under severe water deficit stress. There was a positive high heterosis for the traits examined in some hybrids. Also, in F2 generation even after inbreeding depression, some promising populations displayed appropriate mean performance. These show that the parents used for crossing had rich gene pool for studied traits. Therefore, selection between the individuals of relevant F2 populations could be led to develop high yielding hybrids or transgressed lines.
Pathological and metabolic underpinnings of energetic inefficiency in temporal lobe epilepsy
Authors: He Xiaosong , Caciagli Lorenzo , Parkes Linden , Stiso Jennifer , Karrer Teresa M. , Kim Jason Z. , Lu Zhixin , Menara Tommaso , Pasqualetti Fabio , Sperling Michael R. , Tracy Joseph I. , Bassett Dani S. 
Published: September 2021

AbstractThe human brain consumes a disproportionate amount of energy to generate neural dynamics. Yet precisely how energetic processes are altered in neurological disorders remains far from understood. Here, we use network control theory to profile the brain’s energy landscape, describing the rich dynamical repertoire supported by the structural connectome. This approach allows us to estimate the energy required to activate a circuit, and determine which regions most support that activation. Focusing on temporal lobe epilepsy (TLE), we show that patients require more control energy to activate the limbic network than healthy volunteers, especially ipsilateral to the seizure focus. Further, greater energetic costs are largely localized to the ipsilateral temporo-limbic regions. Importantly, the energetic imbalance between ipsilateral and contralateral temporo-limbic regions is tracked by asymmetric metabolic patterns, which in turn are explained by asymmetric gray matter volume loss. In TLE, failure to meet the extra energy demands may lead to suboptimal brain dynamics and inadequate activation. Broadly, our investigation provides a theoretical framework unifying gray matter integrity, local metabolism, and energetic generation of neural dynamics.
On the hybrid origin of the C2Salsola divaricata agg. (Amaranthaceae) from C3 and C4 parental lineages
Authors: Tefarikis Delphine T. , Morales-Briones Diego F. , Yang Ya , Edwards Gerald , Kadereit Gudrun 
Published: September 2021

AbstractC2 photosynthesis is characterized by recapturing photorespiratory CO2 by RuBisCO in Kranz-like cells and is therefore physiologically intermediate between C3 and C4 photosynthesis. C2 can be interpreted as an evolutionary precursor of C4 and/or as the result of hybridization between a C3 and C4 lineage.We compared the expression of photosynthetic traits among populations of the Salsola divaricata agg. (C2) from humid subtropical to arid habitats on the coasts of the Canary Islands and Morocco and subjected them to salt and drought treatments. We screened for enhanced C4-like expression of traits related to habitat or treatment. We estimated species trees with a transcriptome dataset of Salsoleae and explored patterns of gene tree discordance. With phylogenetic networks and hybridization analyses we tested for hybrid origin of the Salsola divaricata agg.We observed distinct independent variation of photosynthetic traits within and among populations and no clear evidence for selection towards C4-like trait expression in more stressful habitats or treatments. We found reticulation and gene tree incongruence in Salsoleae supporting a putative hybrid origin of the Salsola divaricata agg.C2 photosynthesis in the Salsola divaricata agg. combines traits inherited from its C3 and C4 parental lineages and seems evolutionarily stable, possibly well adapted to a wide climatic amplitude.
A cortico-cortical pathway targets inhibitory interneurons and modulates paw movement during locomotion in mice
Authors: Chang Chia-wei , Zhao Meiling , Grudzien Samantha , Oginsky Max , Yang Yexin , Kwon Sung Eun 
Published: September 2021

AbstractThe primary somatosensory cortex (S1) is important for the control of movement as it encodes sensory input from the body periphery and external environment during ongoing movement. Mouse S1 consists of several distinct sensorimotor subnetworks that receive topographically organized cortico-cortical inputs from distant sensorimotor areas, including the secondary somatosensory cortex (S2) and primary motor cortex (M1). The role of the vibrissal S1 area and associated cortical connections during active sensing is well documented, but whether (and if so, how) non-whisker S1 areas are involved in movement control remains relatively unexplored. Here, we demonstrate that unilateral silencing of the non-whisker S1 area in both male and female mice disrupts hind paw movement during locomotion on a rotarod and a runway. S2 and M1 provide major long-range inputs to this S1 area. Silencing S2 → non-whisker S1 projections alters the hind paw orientation during locomotion while manipulation of the M1 projection has little effect. Using patch-clamp recordings in brain slices from male and female mice, we show that S2 projection preferentially innervates inhibitory interneuron subtypes. We conclude that interneuron-mediated S2–S1 cortico-cortical interactions are critical for efficient locomotion.SignificanceSomatosensory cortex participates in controlling rhythmic movements such as whisking and walking, but the neural circuitry underlying movement control by somatosensory cortex remains relatively unexplored. We uncover a cortico-cortical circuit in primary somatosensory cortex that regulates paw orientation during locomotion in mice. We identify neuronal elements that comprise these cortical pathways using pharmacology, behavioral assays and circuit-mapping methods.
Impedance flow cytometry for viability analysis of Corynebacterium glutamicum
Authors: Hartmann Fabian Stefan Franz , Anastasiou Ioannis , Weiß Tamara , Shen Jing , Seibold Gerd Michael 
Published: September 2021

ABSTRACTCorynebacterium glutamicum efficiently produces glutamate when growth is inhibited. Analyses of viability in this non-growing state requires time consuming plating and determination of colony forming units. We here establish impedance flow cytometry measurements to assess the viability of non-growing, glutamate producing C. glutamicum cultures within minutes.
The mutation effect reaction norm (Mu-RN) highlights environmentally dependent mutation effects and epistatic interactions
Authors: Ogbunugafor C. Brandon 
Published: September 2021

AbstractSince the modern synthesis, the fitness effects of mutations and epistasis have been central yet provocative concepts in evolutionary and population genetics. Studies of how the interactions between parcels of genetic information can change as a function of environmental context have added a layer of complexity to these discussions. Here I introduce the “mutation effect reaction norm” (Mu-RN), a new instrument through which one can analyze the phenotypic consequences of mutations and interactions across environmental contexts. It embodies the fusion of measurements of genetic interactions with the reaction norm, a classic depiction of the performance of genotypes across environments. I demonstrate the utility of the Mu-RN through the signature of a “compensatory ratchet” mutation that undermines reverse evolution of antimicrobial resistance. More broadly, I argue that the mutation effect reaction norm may help us resolve the dynamism and unpredictability of evolution, with implications for theoretical biology, genetic modification technology, and public health.
Parallel systems for social and spatial reasoning within the cortical apex
Authors: Deen Ben , Freiwald Winrich A. 
Published: September 2021

AbstractWhat is the cognitive and neural architecture for high-level reasoning? We hypothesize that systems for understanding people and places remain separate throughout the brain, but share a parallel organization. We test this hypothesis using deep neuroimaging of individual human brains on diverse tasks involving reasoning and memory about familiar people, places, and objects. We find that thinking about people and places elicits responses in distinct areas of high-level association cortex, spanning the frontal, parietal, and temporal lobes. Person- and place-preferring brain regions are systematically yoked across cortical zones. These areas have strongly domain-specific response profiles across visual, semantic, and episodic tasks, and are specifically functionally connected to other parts of association cortex with like category preference. Social and spatial networks are anatomically separated even at the top of the cortical hierarchy, and include parts of cortex with anatomical connections to the hippocampal formation. These results demonstrate parallel, domain-specific networks within the cortical apex. They suggest that domain-specific systems for reasoning constitute components of a broader cortico-hippocampal system for long-term memory.
Neural network modeling of differential binding between wild-type and mutant CTCF reveals putative binding preferences for zinc fingers 1-2
Authors: Kaplow Irene M. , Banerjee Abhimanyu , Foo Chuan Sheng 
Published: September 2021

ABSTRACTBackgroundMany transcription factors (TFs), such as multi zinc-finger (ZF) TFs, have multiple DNA binding domains (DBDs) with multiple components, and deciphering the DNA binding motifs of individual components is a major challenge. One example of such a TF is CCCTC-binding factor (CTCF), a TF with eleven ZFs that plays a variety of roles in transcriptional regulation, most notably anchoring DNA loops. Previous studies found that CTCF zinc fingers (ZFs) 3-7 bind CTCF’s core motif and ZFs 9-11 bind a specific upstream motif, but the motifs of ZFs 1-2 have yet to be identified.ResultsWe developed a new approach to identifying the binding motifs of individual DBDs of a TF through analyzing chromatin immunoprecipitation sequencing (ChIP-seq) experiments in which a single DBD is mutated: we train a deep convolutional neural network to predict whether wild-type TF binding sites are preserved in the mutant TF dataset and interpret the model. We applied this approach to mouse CTCF ChIP-seq data and, in addition to identifying the known binding preferences of CTCF ZFs 3-11, we identified a GAG binding motif for ZF1 and a weak ATT binding motif for ZF2. We analyzed other CTCF datasets to provide additional evidence that ZFs 1-2 interact with the motifs we identified, and we found that the presence of the motif for ZF1 is associated with Ctcf peak strength.ConclusionsOur approach can be applied to any TF for which in vivo binding data from both the wild-type and mutated versions of the TF are available, and our findings provide an unprecedently comprehensive understanding of the binding preferences of CTCF’s DBDs.
Identification of microRNAs in the West Nile virus vector Culex tarsalis
Authors: Asad Sultan , Mehdi Ahmed M. , Pujari Sujit , Rüeckert Claudia , Ebel Gregory D. , Rasgon Jason L. 
Published: September 2021

AbstractBackgroundmicroRNAs (miRNAs) represent a group of small non-coding RNAs that are crucial gene regulators of important biological functions including development and pathogen defense in most living organisms. Presently, there is a lack of availability of information regarding the miRNAs in the mosquito Culex tarsalis, which is one of the most important vectors of West Nile virus (WNV) in the United States. We used small RNA sequencing data and in vitro and in vivo experiments to identify and validate the presence of a repertoire of miRNAs in Cx. tarsalis mosquitoes.ResultsUsing bioinformatic approaches we analyzed small RNA sequencing data from the Cx. tarsalis CT embryonic cell line to discover 86 miRNAs. Consistent with other mosquitoes such as Aedes albopictus and Cx. quinquefasciatus, mi-184 was found to be the most abundant miRNA in Cx tarsalis. We also identified an additional 20 novel miRNAs from the recently sequenced Cx. tarsalis genome, for a total of 106 miRNAs identified in this study. The presence of selected miRNAs was biologically validated in both cell line and adult Cx. tarsalis mosquitoes using RT-qPCR and sequencing.ConclusionsCx. tarsalis is an important vector of many medically important pathogens including WNV and Western Equine encephalitis. Here we report a detailed insight into the miRNA population in Cx. tarsalis mosquitoes. These results will open new avenues of research deciphering the role of miRNAs in different Cx. tarsalis biological events such as development, metabolism, immunity and pathogen infection.
Meta-analysis of immune induced gene expression changes in diverse Drosophila melanogaster innate immune responses
Authors: Waring Ashley L. , Hill Joshua , Allen Brooke M. , Bretz Nicholas M. , Le Nguyen , Kr Pooja , Fuss Dakota , Mortimer Nathan T. 
Published: September 2021

AbstractBackgroundOrganisms are commonly infected by a diverse array of pathogen types including bacteria, fungi, viruses, and parasites, and mount functionally distinct responses to each of these varied immune challenges. Host immune responses are characterized by the induction of gene expression in response to infection. However, the extent to which expression changes are shared among responses to distinct pathogens is largely unknown.ResultsWe performed meta-analysis of gene expression data collected from Drosophila melanogaster following infection with a wide array of pathogens. We identified 62 genes that are significantly induced by infection. While many of these infection-induced genes encode known immune response factors, we also identified 21 genes that have not been previously associated with host immunity. Examination of the upstream flanking sequences of the infection-induced genes lead to the identification of two conserved enhancer sites. These sites correspond to conserved binding sites for GATA and nuclear factor κB (NFκB) family transcription factors and are associated with higher levels of transcript induction. We further identified 31 genes with predicted functions in metabolism and organismal development that are significantly downregulated following infection by diverse pathogens.ConclusionsOur study identifies conserved gene expression changes in Drosophila melanogaster following infection with varied pathogens, and transcription factor families that may regulate this immune induction. These findings provide new insight into transcriptional changes that accompany Drosophila immunity. They may suggest possible roles for the differentially regulated genes in innate immune responses to diverse classes of pathogens, and serve to identify candidate genes for further empirical study of these processes.
BindVAE: Dirichlet variational autoencoders for de novo motif discovery from accessible chromatin
Authors: Kshirsagar Meghana , Yuan Han , Ferres Juan Lavista , Leslie Christina 
Published: September 2021

AbstractWe present a novel unsupervised deep learning approach called BindVAE, based on Dirichlet variational autoencoders, for jointly decoding multiple TF binding signals from open chromatin regions. BindVAE can disentangle an input DNA sequence into distinct latent factors that encode cell-type specific in vivo binding signals for individual TFs, composite patterns for TFs involved in cooperative binding, and genomic context surrounding the binding sites. For the task of retrieving motifs of expressed TFs for a given cell type, we find that BindVAE has a higher precision, albeit lower recall, compared to other motif discovery approaches.
Multi-context genetic modeling of transcriptional regulation resolves novel disease loci
Authors: Thompson Mike , Gordon Mary Grace , Lu Andrew , Tandon Anchit , Halperin Eran , Gusev Alexander , Ye Chun Jimmie , Balliu Brunilda , Zaitlen Noah 
Published: September 2021

AbstractA majority of the variants identified in genome-wide association studies fall in non-coding regions of the genome, indicating their mechanism of impact is mediated via gene expression. Leveraging this hypothesis, transcriptome-wide association studies (TWAS) have assisted in both the interpretation and discovery of additional genes associated with complex traits. However, existing methods for conducting TWAS do not take full advantage of the intra-individual correlation inherently present in multi-context expression studies and do not properly adjust for multiple testing across contexts. We developed CONTENT— a computationally efficient method with proper cross-context false discovery correction that leverages correlation structure across contexts to improve power and generate context-specific and context-shared components of expression. We applied CONTENT to bulk multi-tissue and single-cell RNA-seq data sets and show that CONTENT leads to a 42% (bulk) and 110% (single cell) increase in the number of genetically predicted genes relative to previous approaches. Interestingly, we find the context-specific component of expression comprises 30% of heritability in tissue-level bulk data and 75% in single-cell data, consistent with cell type heterogeneity in bulk tissue. In the context of TWAS, CONTENT increased the number of gene-phenotype associations discovered by over 47% relative to previous methods across 22 complex traits.
JaponicusDB: Rapid deployment of a model organism database for an emerging model species
Authors: Rutherford Kim M. , Harris Midori A. , Oliferenko Snezhana , Wood Valerie 
Published: September 2021

AbstractThe fission yeast Schizosaccharomyces japonicus has recently emerged as a powerful system for studying the evolution of essential cellular processes, drawing on similarities as well as key differences between S. japonicus and the related, well-established model Schizosaccharomyces pombe. We have deployed the open-source, modular code and tools originally developed for PomBase, the S. pombe model organism database (MOD), to create JaponicusDB (www.japonicusdb.org), a new MOD dedicated to S. japonicus. By providing a central resource with ready access to a growing body of experimental data, ontology-based curation, seamless browsing and querying, and the ability to integrate new data with existing knowledge, JaponicusDB supports fission yeast biologists to a far greater extent than any other source of S. japonicus data. JaponicusDB thus enables S. japonicus researchers to realise the full potential of studying a newly emerging model species, and illustrates the widely applicable power and utility of harnessing reusable PomBase code to build a comprehensive, community-maintainable repository of species-relevant knowledge.