bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting global influence of transcription factor interactions on gene expression in lymphoblastoid cells using neural network models
Authors: Patel Neel , Bush William S. 
Published: June 2021

AbstractBackgroundTranscription factor(TF) interactions are known to regulate target gene(TG) expression in eukaryotes via TF regulatory modules(TRMs). Such interactions can be formed due to co-localizing TFs binding proximally to each other in the DNA sequence or over long distances between distally binding TFs via chromatin looping. While the former type of interaction has been characterized extensively, long distance TF interactions are still largely understudied. Furthermore, most prior approaches have focused on characterizing physical TF interactions without accounting for their effects on TG expression regulation. Understanding TRM based TG expression regulation could aid in understanding diseases caused by disruptions to these mechanisms. In this paper, we present a novel neural network based TRM detection approach that consists of using multi-omics TF based regulatory mechanism information to generate features for building non-linear multilayer perceptron TG expression prediction models in the GM12878 immortalized lymphoblastoid cells.ResultsWe estimated main effects of 149 individual TFs and interaction effects of 48 distinct combinations of TFs forming TRMs based on their influence on TG expression. We identified several well-known and discovered multiple previously uncharacterized TF interactions within our detected set of TRMs. We further characterized the pairwise TRMs using long distance chromatin looping and motif co-occurrence data. We found that nearly all the TFs constituting TRMs detected by our approach interacted via chromatin looping, and that these TFs further interacted with promoters to influence TG expression through one of four possible regulatory configurations.ConclusionHere, we have provided a framework for detecting TRMs using neural network models containing multi-omics TF based regulatory features. We have also described these TRMs based on their regulatory potential along with presenting evidence for the possibility of TF interactions forming the TRMs occurring via chromatin looping.
Communication between the mediodorsal thalamus and prelimbic cortex regulates timing performance in rats
Authors: De Corte Benjamin J. , Heslin Kelsey A. , Cremers Nathan S. , Freeman John H. , Parker Krystal L. 
Published: June 2021

AbstractPredicting when future events will occur and adjusting behavior accordingly is critical to adaptive behavior. Despite this, little is known about the brain networks that encode time and how this ultimately impacts decision-making. One established finding is that the prefrontal cortex (PFC) and its non-human analogues (e.g., the rodent prelimbic cortex; PL) mediate timing. This provides a starting point for exploring the networks that support temporal processing by identifying areas that interact with the PFC during timing tasks. For example, substantial work has explored the role of frontostriatal circuits in timing. However, other areas are undoubtedly involved. The mediodorsal nucleus of the thalamus (MD) is an excellent candidate region. It shares dense, reciprocal connections with PFC-areas in both humans and non-human species and is implicated in cognition. However, causal data implicating MD-PFC interactions in cognition broadly is still sparse, and their role in timing specifically is currently unknown. To address this, we trained male rats on a time-based, decision-making task referred to as the ‘peak-inter- val’ procedure. During the task, presentation of a cue instructed the rats to respond after a specific interval of time elapsed (e.g., tone-8 seconds). We incorporated two cues; each requiring a response after a distinct time-interval (e.g., tone-8 seconds / light-16 seconds). We tested the effects of either reversibly inactivating the MD or PL individually or functionally disconnecting them on performance. All manipulations caused a comparable timing deficit. Specifically, responses showed little organization in time, as if primarily guided by motivational systems. These data expand our understanding of the networks that support timing and suggest that MD-PL interactions specifically are a core component. More broadly, our results suggest that timing tasks provide a reliable assay for characterizing the role of MD-PL interactions in cognition using rodents, which has been difficult to establish in the past.
Economic Choices under Simultaneous or Sequential Offers Rely on the Same Neural Circuit
Authors: Shi Weikang , Ballesta Sébastien , Padoa-Schioppa Camillo 
Published: June 2021

AbstractA series of studies in which monkeys chose between two juices offered in variable amounts identified in the orbitofrontal cortex (OFC) different groups of neurons encoding the value of individual options (offer value), the binary choice outcome (chosen juice) and thechosen value. These variables capture both the input and the output of the choice process, suggesting that the cell groups identified in OFC constitute the building blocks of a decision circuit. Several lines of evidence support this hypothesis. However, in previous experiments offers were presented simultaneously, raising the question of whether current notions generalize to when goods are presented or are examined in sequence. Recently, Ballesta and Padoa-Schioppa (2019) examined OFC activity under sequential offers. An analysis of neuronal responses across time windows revealed that a small number of cell groups encoded specific sequences of variables. These sequences appeared analogous to the variables identified under simultaneous offers, but the correspondence remained tentative. Thus in the present study we examined the relation between cell groups found under sequential versus simultaneous offers. We recorded from the OFC while monkeys chose between different juices. Trials with simultaneous and sequential offers were randomly interleaved in each session. We classified cells in each choice modality and we examined the relation between the two classifications. We found a strong correspondence – in other words, the cell groups measured under simultaneous offers and under sequential offers were one and the same. This result indicates that economic choices under simultaneous or sequential offers rely on the same neural circuit.Significance StatementResearch in the past 20 years has shed light on the neuronal underpinnings of economic choices. A large number of results indicates that decisions between goods are formed in a neural circuit within the orbitofrontal cortex (OFC). In most previous studies, subjects chose between two goods offered simultaneously. Yet, in daily situations, goods available for choice are often presented or examined in sequence. Here we recorded neuronal activity in the primate OFC alternating trials under simultaneous and under sequential offers. Our analyses demonstrate that the same neural circuit supports choices in the two modalities. Hence current notions on the neuronal mechanisms underlying economic decisions generalize to choices under sequential offers.
A compendium of novel genomics technologies provides a chromosome-scale assembly and insights into the sex determining system of the Greenland Halibut
Authors: Ferchaud A-L , Mérot C , Normandeau E , Ragoussis I , Babin C , Djambazian H , Bérubé P , Audet C , Treble M , Walkusz W , Bernatchez L 
Published: June 2021

ABSTRACTDespite the commercial importance of Greenland Halibut (Reinhardtius hippoglossoides), important gaps still persist in our knowledge of this species, including its reproductive biology and sex determination mechanism. In this study, we combined single molecule sequencing of long reads (Pacific Sciences) with Chromatin Conformation Capture sequencing (Hi-C) data to provide the first chromosome-level genome reference for this species. The high-quality assembly encompassed more than 598 Megabases (Mb) assigned to 1 594 scaffolds (scaffold N50 = 25 Mb) with 96 % of its total length distributed among 24 chromosomes. The investigation of its syntenic relationships with other economically important flatfish species revealed a high conservation of synteny blocks among members of this phylogenetic clade. Sex determination analysis revealed that flatfishes do not escape the rule applied to other teleost fish and exhibit a high level of plasticity and turnover in sex-determination mechanisms. A whole-genome sequence analysis of 198 individuals allowed us to draw a full picture of the molecular sex determination (SD) system for Greenland Halibut, revealing that this species possesses a very nascent male heterogametic XY system, with a putative major effect of the sox2 gene, also described as the main SD driver in two other flatfishes. Interestingly, our study also suggested for the first time in flatfishes that a putative Y-autosomal fusion could be associated with a reduction of recombination typical of early steps of sex chromosome evolution.
The percentage of Monocytes CD39+ is higher in Pregnant COVID-19 than in Non-Pregnant COVID-19 patients
Authors: Cérbulo-Vázquez A. , García-Espinosa M. , Briones-Garduño J.C. , Arriaga-Pizano L. , Ferat-Osorio E. , Zavala-Barrios B. , Cabrera-Rivera G.L. , Miranda-Cruz P. , García de la Rosa M.T. , Prieto-Chávez J.L. , Rivero-Arredondo V. , Madera-Sandoval R.L. , Cruz-Cruz A. , Salazar-Rios E. , Salazar-Rios ME , Serrano-Molina D , De Lira-Barraza R. C. , Villanueva-Compean A. H. , Esquivel-Pineda A. , Ramirez-Montes de Oca R. , Caldiño-Soto F. , Ramírez-García L.A. , Flores-Padilla G. , Moreno-Álvarez O. , Guerrero-Avendaño GML , López-Macías C. 
Published: June 2021

AbstractCurrent medical guidelines consider COVID-19 pregnant women a high-risk group. Physiological gestation down regulates the immunological response to maintain “maternal-fetal tolerance”; hence, a SARS-CoV-2 infection constitutes a potentially threatening condition to both the mother and the fetus. To establish the immune profile in pregnant COVID-19+ patients a cross-sectional study was conducted. Leukocyte immunophenotype, mononuclear leukocyte response to polyclonal stimulus and cytokine/chemokine serum concentration were analyzed in pregnant fifteen COVID-19+ and control groups (fifteen non-pregnant COVID-19+, and thirteen pregnant COVID-19-women). Pregnant COVID-19+ patients exhibit lower percentages of monocytes HLA-DR+ compared with control groups. Nevertheless, pregnant COVID-19+ women show a higher percentage of monocytes CD39+ than controls. Furthermore, a higher concentration of TNF-α, IL-6, MIP1b and IL-4 was observed within the pregnant COVID-19+ group. Our result shows that pregnant women express immunological characteristics that potentially mediate the immune response in COVID-19.
Phylogenetic study of thermophilic genera Anoxybacillus, Geobacillus, Parageobacillus, and proposal of a new classification Quasigeobacillus gen. nov
Authors: Talamantes-Becerra Berenice , Carling Jason , Blom Jochen , Georges Arthur 
Published: June 2021

AbstractA phylogenetic study of Anoxybacillus, Geobacillus and Parageobacillus was performed using publicly available whole genome sequences. A total of 113 genomes were selected for phylogenomic metrics including calculation of Average Nucleotide Identity (ANI) and Average Amino acid Identity (AAI), and a maximum likelihood tree was built from alignment of a set of 662 orthologous core genes. The combined results from the core gene tree and ANI and AAI dendrograms show that the genomes split into two main clades, clade I containing all Geobacillus, all Parageobacillus and some species of Anoxybacillus, and clade II, containing the majority of Anoxybacillus species. Clade I is further partitioned into three clades, consisting separately of Geobacillus, Parageobacillus, and a third clade which we suggest should be elevated to a new genus Quasigeobacillus gen. nov. Two species of Anoxybacillus showed inconsistent positioning among the trees produced by differing methods and could not be clearly resolved into any of the three existing genera or the new genus. This research shows the importance of considering closely related genera together when studying phylogeny or assigning genomic affinities.
Robust Brain State Decoding using Bidirectional Long Short Term Memory Networks in functional MRI
Authors: Mittal Anant , Aggarwal Priya , Pessoa Luis , Gupta Anubha 
Published: June 2021

AbstractDecoding brain states of the underlying cognitive processes via learning discriminative feature representations has recently gained a lot of interest in brain imaging studies. Particularly, there has been an impetus to encode the dynamics of brain functioning by analyzing temporal information available in the fMRI data. Long-short term memory (LSTM), a class of machine learning model possessing a “memory” component, is increasingly being observed to perform well in various applications with dynamic temporal behavior, including brain state decoding. Because of the dynamics and inherent latency in fMRI BOLD responses, future temporal context is crucial. However, it is neither encoded nor captured by the conventional LSTM model. This paper performs robust brain state decoding via information encapsulation from both the past and future instances of fMRI data via bi-directional LSTM. This allows for explicitly modeling the dynamics of BOLD response without any delay adjustment. The two hidden activations of forward and reverse directions in bi-LSTM are collated to build the “memory” of the model and are used to robustly predict the brain states at every time instance. Working memory data from the Human Connectome Project (HCP) is utilized for validation and was observed to perform 18% better than it’s unidirectional counterpart in terms of accuracy in predicting the brain states.
Flexible seed size enables ultra-fast and accurate read alignment
Authors: Sahlin Kristoffer 
Published: June 2021

Read alignment to genomes is a fundamental computational step used in many bioinformatic analyses, and often, it is the computational bottleneck. Therefore, it is desirable to perform the alignment step as fast as possible without compromising accuracy. Most alignment algorithms consider a seed-and-extend approach, where the time-consuming seeding step identifies and decides on candidate mapping locations. Recently, several advances have been made on seeding methods for fast sequence comparison.We combine two such methods, syncmers and strobemers, in a novel seeding approach for constructing dynamic-sized fuzzy seeds and implement the method in a short-read aligner, strobealign. Firstly, we show that our seeding is fast to construct and effectively reduces repetitiveness in the seeding step using a novel metric E-hits. Secondly, we benchmark strobealign to traditional and recently proposed aligners on simulated and biological data and show that strobealign is several times faster than traditional aligners such as BWA and Bowtie2 at similar and sometimes higher accuracy while being both faster and more accurate than more recently proposed aligners. Our aligner can free up substantial time and computing resources needed for read alignment in many pipelines.Availabilityhttps://github.com/ksahlin/strobealign.
Requirement for an Otopetrin-Like protein for acid taste in Drosophila
Authors: Ganguly Anindya , Chandel Avinash , Turner Heather , Wang Shan , Liman Emily R. , Montell Craig 
Published: June 2021

AbstractMany of the Drosophila receptors required for bitter, sugar and other tastes have been identified. However, the receptor required for the taste of acid has been elusive. In Drosophila, the major families of taste receptors, such as “Gustatory Receptors” and “Ionotropic Receptors” are unrelated to taste receptors in mammals. Previous work indicated that members of these major families do not appear to be broadly required acid sensors. Here, to identify the enigmatic acid taste receptor, we interrogated three genes encoding proteins distantly related the mammalian Otopertrin1 proton channel. We found that RNAi knockdown or mutation of Otopetrin-Like A (OtopLA) by CRISPR/Cas9, severely impairs the behavioral rejection of sugary foods laced with HCl or carboxylic acids. Mutation of OtopLA also greatly reduces acid-induced action potentials. We identified an isoform of OtopLA that was expressed in the proboscis and was sufficient to restore acid sensitivity to OtopLA mutant flies. OtopLA functioned in acid taste in a subset of bitter-activated gustatory receptor neurons that senses protons. This work highlights an unusual functional conservation of a receptor required for a taste modality in flies and mammals.
IKZF3 deficiency potentiates chimeric antigen receptor T cells targeting solid tumors
Authors: Zou Yan , Chi Tian 
Published: June 2021

AbstractChimeric antigen receptor (CAR) T cell therapy has been successful in treating hematological malignancy, but solid tumors remain refractory. Here, we demonstrated that knocking out transcription factor IKZF3 in HER2-specific CAR T cells targeting breast cancer cells did not affect proliferation or differentiation of the CAR T cells in the absence of tumors, but markedly enhanced killing of the cancer cellsin vitroand in a xenograft model. Furthermore,IKZF3KO had similar effects on the CD133-specific CAR T cells targeting glioblastoma cells. AlphaLISA and RNA-seq analyses indicate thatIKZF3KO increased the expression of genes involved in cytokine signaling, chemotaxis and cytotoxicity. Our results suggest a general strategy for enhancing CAR T efficacy on solid tumors.
Understanding the mechanism of monoADP ribosylation in OsSRT1 and its linkage to DNA repair system under stress conditions
Authors: Mitra Nilabhra , Dey Sanghamitra 
Published: June 2021

AbstractThe role of sirtuins in plants are slowly unraveling. There are only reports of H3K9Ac deacetylation by OsSRT1. Here our studies shade light on its dual enzyme capability with preference for mono ADP ribosylation over deacetylation. OsSRT1 can specifically transfer the single ADP ribose group on its substrates in an enzymatic manner. This mono ADPr effect is not well known in plants, more so for deacetylases. The products of this reaction (NAM and ADP ribose) have immense negative effect on this enzyme suggesting a tighter regulation. Resveratrol, a natural plant polyphenol proves to be a strong activator of this enzyme at 150 μM concentration. Under different abiotic stress conditions, we could link this ADP ribosylase activity to the DNA repair pathway by activating the enzyme PARP1. Metal stress in plants also influences these enzyme activities.HighlightsOsSRT1 can transfer a single moiety of ADP-ribose on itself as well as other nuclear proteins like histones H3 and H2A.NAM, ADP-ribose and certain metal ions negatively regulate this ADP-ribose transfer.ADPr of OsPARP1 and OsPARP2 links OsSRT1 to DNA damage repair pathways.OsSRT1 positively regulates the activity of OsPARP1 by ADP ribosylating it.On plant’s exposure to H2O2(oxidative stress) and Arsenic toxicity, there is a link between the increased activity of the players of DNA damage repair system and overexpression of OsSRT1.
Tracking the Brain’s Intrinsic Connectivity Networks in EEG
Authors: Shaw Saurabh Bhaskar , McKinnon Margaret C. , Heisz Jennifer J. , Harrison Amabilis H. , Connolly John F. , Becker Suzanna 
Published: June 2021

AbstractFunctional magnetic resonance imaging (fMRI) has identified dysfunctional network dynamics underlying a number of psychopathologies, including post-traumatic stress disorder, depression and schizophrenia. There is tremendous potential for the development of network-based clinical biomarkers to better characterize these disorders. However, to realize this potential requires the ability to track brain networks using a more affordable imaging modality, such as Electroencephalography (EEG). Here we present a novel analysis pipeline capable of tracking brain networks from EEG alone, after training on supervisory signals derived from data simultaneously recorded in EEG and fMRI, while people engaged in various cognitive tasks. EEG-based features were then used to classify three cognitively-relevant brain networks with up to 75% accuracy. These findings could lead to affordable and non-invasive methods to objectively diagnose brain disorders involving dysfunctional network dynamics, and to track and even predict treatment responses.
Cell culture evolution of a HSV-1/VZV UL34/ORF24 chimeric virus reveals novel functions for HSV genes in capsid nuclear egress
Authors: Roller Richard J. , Hassman Tineke , Haugo-Crooks Alison 
Published: June 2021

AbstractHSV and VZV are both members of the alphaherpesvirus subfamily, but are of different genera. Substitution of the HSV-1 UL34 coding sequence with that of its VZV homolog, ORF24, results in a virus that has defects in viral growth, spread, capsid egress, and nuclear lamina disruption very similar to those seen in a UL34-null virus despite normal interaction between ORF24 protein and HSV pUL31 and proper localization of the NEC at the nuclear envelope. Minimal selection for growth in cell culture resulted in viruses that grew and spread much more efficiently that the parental chimeric virus. These viruses varied in their ability to support nuclear lamina disruption, normal NEC localization and capsid de-envelopment. Single mutations that suppress the growth defect were mapped to the coding sequences of ORF24, ICP22 and ICP4 and one virus carried single mutations in each of the ICP22 and US3 coding sequences. The phenotypes of these viruses support a role for ICP22 in nuclear lamina disruption and a completely unexpected role for the major transcriptional regulator, ICP4, in capsid nuclear egress.ImportanceInteractions among virus proteins are critical for assembly and egress of virus particles, and such interactions are attractive targets for antiviral therapy. Identification of critical functional interactions can be slow and tedious. Capsid nuclear egress of herpesviruses is a critical event in the assembly and egress pathway and is mediated by two proteins that are conserved among herpesviruses, pUL31 and pUL34. Here we describe a cell culture evolution approach to identify other viral gene products that functionally interact with pUL34.
Measles fusion complexes from central nervous system clinical isolates: decreased interaction between hemagglutinin and fusion proteins
Authors: Mathieu Cyrille , Figueira Tiago Nascimento , Decker Amanda R. , Ferren Marion , Bovier Tiziana F. , Jurgens Eric M. , Marcink Tara C. , Moscona Anne , Porotto Matteo 
Published: June 2021

AbstractMeasles virus (MeV) viral entry is mediated by a fusion complex comprised of a receptor binding protein (hemagglutinin, H) and a fusion protein (F). The wild type H/F complex requires interaction with specific proteinaceous receptors (CD150/SLAM and nectin-4) in order to be activated. In contrast the H/F complexes isolated from viruses infecting the central nervous system (CNS) do not require a specific receptor. A single amino acid change in the F protein (L454W) was previously identified in two patients with lethal sequelae of MeV CNS infection, and the F bearing this mutation mediates fusion even without the H protein. We show here that viruses bearing the L454W fusion complex are less efficient than wt virus at targeting receptor expressing cells and that this defect is associated with a decreased interaction between the H and the F proteins.ImportanceMeasles (Mev) infection can cause serious complications including measles inclusion body encephalitis (MIBE) and subacute sclerosing panencephalitis (SSPE). MIBE and SSPE are relatively rare but lethal. We have shown that the fusion complex of CNS adapted clinical samples can spread in the absence of known receptor. We now provide evidence that HRC mutations leading to CNS adaptation come at a cost to the efficiency of viral entry.One Sentence SummaryMeasles CNS adapted fusion complexes have altered H/F interaction.