bluuebunny/crossref_metadata_2025_split huggingface dataset:
TreeProfiler: A command-line tool for computing and visualizing phylogenetic profiles against large trees
Authors: Deng Ziqi , Hernández-Plaza Ana , Huerta-Cepas Jaime 
Published: September 2023

ABSTRACTPhylogenetic profiling is a common bioinformatics approach used to study the distribution of traits across species or, more broadly, along the topology of a phylogenetic tree. Originally proposed as a technique for establishing functional relationships between various genes through their correlated presence/absence patterns, phylogenetic profiling is currently considered a powerful exploration tool for investigating the evolutionary distribution of nearly any trait across both gene or species phylogenies. However, computing and visualizing phylogenetic profiles based on large trees is a laborious task. First, traits need to be mapped against tree nodes, which usually requires the implementation ofad hocscripts or substantial manual work. Second, tree mapping is often limited to leaf nodes, neglecting the usefulness of profiling traits against internal tree nodes. Lastly, graphical exploration of large phylogenetic tree-based profiles is challenging, as plotting usually requires complex manual adjustments and most visualization tools cannot scale to the size and complexity of current datasets. To address these limitations, we have developed TreeProfiler, a command line tool designed to facilitate both the automated annotation of large trees using a wide range of data sources, and the visual exploration of these annotations as phylogenetic profiles. TreeProfiler enables seamless annotation of massive trees and data tables, including built-in support for functional data, taxonomic information, multiple sequence alignments and protein domain architectures. Importantly, TreeProfiler expands its annotation capabilities beyond tree leaves, enabling the annotation of internal nodes with summarized or consensus information under each branch. Additionally, TreeProfiler offers a predefined set of graphical layouts that are based on the ETE Toolkit v4.0 library. TreeProfiler offers unique capabilities that extend and facilitate the use of phylogenetic profiling techniques for a broad landscape of scenarios and for a wide community of researchers interested in evolutionary analysis. To demonstrate its value, we showcase TreeProfiler by automatically profiling multiple data sources across a large bacterial phylogeny including 45,555 species, and by exploring functional and taxonomic annotations over a large gene family tree. TreeProfiler is available athttps://github.com/compgenomicslab/TreeProfiler.
Brief Apnea and Hypoventilation Reduces Seizure Duration and Shifts Seizure Location for Several Hours in a Model of Severe Traumatic Brain Injury
Authors: Rodriguez Lara Frances , Sunkavalli Praneel , Mikaelian Michael , Golemb Bryan , Staley Kevin , Costine-Bartell Beth 
Published: September 2023

ABSTRACTObjectiveSeizures are difficult to control in infants and toddlers. Seizures with periods of apnea and hypoventilation are common following severe traumatic brain injury (TBI). In our multifactorial, severe TBI model (cortical impact, mass effect, subdural hematoma, subarachnoid hemorrhage, seizures induced with kainic acid, and brief apnea and hypoventilation), we observed that brief apnea with hypoventilation (A&H) after induced seizure acutely interrupted seizures, leading us to hypothesize that brief A&H might reduce seizure duration beyond the brief hypoxia and hypercapnia for several hours thereafter. The effects of the timing of A&H on seizure duration and location might inform the pathophysiology of this hypoxic-ischemic injury as well as potential treatments.MethodsPiglets (1 week or 1 month old) received multi-factorial injuries. Apnea and hypoventilation (1 min apnea, 10 min hypoventilation; A&H) was induced either before or after seizure induction, or as a control piglets received subdural/subarachnoid hematoma and seizure without A&H. In an intensive care unit, piglets were sedated, intubated, mechanically ventilated, and epidural EEG was recorded for an average of 18 hours after seizure induction.ResultsIn our severe TBI model, A&H after seizure reduced ipsilateral seizure burden by 80% compared to the same injuries without A&H. In the A&H before seizure induction group, more piglets had exclusively contralateral seizures though most piglets in all groups had seizures that shifted location throughout the several hours of seizure. After 8-10 hours, seizures transitioned to interictal epileptiform discharges regardless of timing of A&H.SignificanceEven brief A&H may alter traumatic seizures We will address the possibility of induced spreading depolarization prior to preclinical investigations of hypercapnia with normoxia, with controlled intracranial pressure, as a therapeutic option for children with status epilepticus after hemorrhagic TBI.
TheSilene latifoliagenome and its giant Y chromosome
Authors: Moraga Carol , Branco Catarina , Rougemont Quentin , Veltsos Paris , Jedlička Pavel , Muyle Aline , Hanique Melissa , Tannier Eric , Liu Xiaodong , Mendoza-Galindo Eddy , Lemaitre Claire , Fields Peter D. , Cruaud Corinne , Labadie Karine , Belser Caroline , Briolay Jerome , Santoni Sylvain , Cegan Radim , Linheiro Raquel , de la Vega Ricardo C. Rodríguez , Adam Gabriele , Filali Adil El , Mossion Vinciane , Boualem Adnane , Tavares Raquel , Chebbi Amine , Cordaux Richard , Fruchard Cécile , Prentout Djivan , Velt Amandine , Spataro Bruno , Delmotte Stephane , Weingartner Laura , Toegelová Helena , Tulpová Zuzana , Cápal Petr , Šimková Hana , Štorchová Helena , Krüger Manuela , Abeyawardana Oushadee A. J. , Taylor Douglas R. , Olson Matthew S. , Sloan Daniel B. , Karrenberg Sophie , Delph Lynda F. , Charlesworth Deborah , Giraud Tatiana , Bendahmane Abdelhafid , Genova Alex Di , Madoui Amin , Hobza Roman , Marais Gabriel A. B. 
Published: September 2023

AbstractIn some species, the Y is a tiny chromosome but the dioecious plantSilene latifoliahas a giant ∼550 Mb Y chromosome, which has remained unsequenced so far. Here we used a hybrid approach to obtain a high-quality maleS. latifoliagenome. Using mutants for sexual phenotype, we identified candidate sex-determining genes on the Y. Comparative analysis of the sex chromosomes with outgroups showed the Y is surprisingly rearranged and degenerated for a ∼11 MY-old system. Recombination suppression between X and Y extended in a stepwise process, and triggered a massive accumulation of repeats on the Y, as well as in the non-recombining pericentromeric region of the X, leading to giant sex chromosomes.One-Sentence SummaryThis work uncovers the structure, function, and evolution of one of the largest giant Y chromosomes, that of the model plantSilene latifolia, which is almost 10 times larger than the human Y, despite similar genome sizes.
tidytcells: standardizer for TCR/MHC nomenclature
Authors: Nagano Yuta , Chain Benjamin 
Published: September 2023

AbstractT cell receptors (TCRs) underpin the diversity and specificity of T cell activity. As such, TCR repertoire data is valuable both as an adaptive immune biomarker, and as a way to identify candidate therapeutic TCRs. Analysis of TCR repertoires relies heavily on computational analysis, and therefore it is of vital importance that the data is standardized and computer-readable. However in practice, the usage of different abbreviations and non-standard nomenclature in different datasets makes this data pre-processing non-trivial.tidytcellsis a lightweight, platform-independent Python package that provides easy-to-use standardization tools specifically designed for TCR nomenclature. The software isopen-sourcedunder the MIT license and is available to install from thePython Package Index (PyPI).
Epigenetic modification and characterization of theMGMTpromoter region using CRISPRoff in glioblastoma cells
Authors: Weber Remi , Weller Michael , Reifenberger Guido , Vasella Flavio 
Published: September 2023

AbstractThe methylation status of the O6-methylguanine DNA methyltransferase (MGMT) promoter region is a critical predictor of response to alkylating agents in glioblastoma. However, current approaches to study theMGMTstatus focus on analyzing models with non-identical backgrounds. Here, we present an epigenetic editing approach using CRISPRoff to introduce site-specific CpG methylation in theMGMTpromoter region of glioma cell lines. Sanger sequencing revealed successful introduction of methylation, effectively generating differently methylated glioma cell lines with an isogenic background. The introduced methylation resulted in reduced MGMT mRNA and protein levels. Furthermore, the cell lines withMGMTpromoter region methylation exhibited increased sensitivity to temozolomide, consistent with the impact of methylation on treatment outcomes in patients with glioblastoma. This precise epigenome-editing approach provides valuable insights into the functional relevance ofMGMTpromoter regional methylation and its potential for prognostic and predictive assessments, as well as epigenetic-targeted therapies.
Oncogenic functions of the m6A demethylase FTO in breast cancer cells involving translational upregulation of C/EBPβ-LIP
Authors: Zuidhof Hidde R. , Müller Christine , Kortman Gertrud , Wardenaar René , Stepanova Ekaterina , Loayza-Puch Fabricio , Calkhoven Cornelis F. 
Published: September 2023

AbstractN6-methyladenosine (m6A) is a prevalent posttranscriptional mRNA modification involved in the regulation of transcript turnover, translation, and other aspects of RNA fate. The modification is mediated by multicomponent methyltransferase complexes (so-called writers) and is reversed through the action of the m6A-demethylases fat mass and obesity-associated (FTO) and alkB homolog 5 (ALKBH5) (so-called erasers). FTO promotes cell proliferation, colony formation and metastasis in models of triple-negative breast cancer (TNBC). However, little is known about genome-wide or specific downstream regulation by FTO. Here, we examined changes in the genome-wide transcriptome and translatome following FTO-knockdown in TNBC cells. Unexpectedly, FTO knockdown had a limited effect on the translatome, while transcriptome analysis revealed that genes related to extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) are being regulated through yet unidentified mechanisms. Differential translation of the CEBPB mRNA into the C/EBPβ transcription factor isoform C/EBPβ-LIP is known to act pro-oncogenic in TNBC cells through regulation of EMT genes. Here we show that FTO is required for efficient C/EBPβ-LIP expression, suggesting that FTO has oncogenic functions through regulation of C/EBPβ-LIP.
Optimizing magnetometers arrays and analysis pipelines for multivariate pattern analysis
Authors: Bezsudnova Yulia , Quinn Andrew J. , Jensen Ole 
Published: September 2023

AbstractBackgroundMultivariate pattern analysis (MVPA) has proven an excellent tool in cognitive neuroscience used M/EEG, and MRI. It also holds a strong promise when applied to optically-pumped magnetometer-based magnetoencephalography.New methodTo optimize OPM-MEG systems for MVPA experiments this study examines data from a conventional MEG magnetometer array, focusing on appropriate noise reduction techniques for magnetometers. We also determined the least required number of sensors needed for robust MVPA for image categorization experiments.ResultsWe found that the use of signal space separation (SSS) significantly lowered the classification accuracy considering a sub-array of 102 magnetometers or a sub-array of 204 gradiometers. We also found that classification accuracy did not improve when going beyond 30 sensors irrespective of whether SSS has been applied.Comparison with existing methodsThe power spectra of data filtered with SSS has a substantially higher noise floor that data cleaned with SSP or HFC. Consequently, the MVPA decoding results obtained from the SSS-filtered data are significantly lower compared to all other methods employed.ConclusionsWhen designing an MEG system based on SQUID magnetometers optimized for multivariate analysis for image categorization experiments, about 30 magnetometers are sufficient. We advise against applying SSS filters to data from MEG and OPM systems prior to performing MVPA as this method, albeit reducing low-frequency external noise contributions, also introduces an increase in broadband noise. We recommend employing noise reduction techniques that either decrease or maintain the noise floor of the data like signal-space projection, homogeneous field correction and gradient noise reduction.HighlightsA sensor array of about 30 sensors is sufficient for multivariate pattern analysis using conventional MEG magnetometers for image classification.Using signal space separation filter on magnetometer data prior to multivariate pattern analysis might reduce classification accuracy due to an increase in white noise in the data contributed by the algorithm.When performing multivariate data analysis, other noise reduction approaches that diminish the contribution of external noise sources and reduce the variance of the data are advisable such as synthetic gradiometers, signal space projection or homogeneous field correction.
Unraveling the role ofXistin X chromosome inactivation: insights from rabbit model and deletion analysis of exons and repeat A
Authors: Liang Mingming , Zhang Lichao , Lai Liangxue , Li Zhanjun 
Published: September 2023

AbstractX chromosome inactivation (XCI) is a dosage compensation process that aims to equalize the expression of X-linked genes between males and females. Initiation of XCI relies onXist, which is continuously expressed in somatic cells during XCI maintenance. HowXistimpacts XCI maintenance remains unclear, and its functional motifs remain unclear. In this study, we conducted a comprehensive analysis of theXist. The results demonstrate that rabbits serve as an ideal non-primate animal model for investigating the functions ofXistin vivo. And homozygous knockout of exon 1, exon 6 and repeat A in females resulted in embryonic lethality. However, XΔReAX females withXistexpression from the intact X chromosome, did not display any abnormalities. Interestingly, there were no significant differences between females with homozygous knockout of exons 2-5 and wild-type rabbits. This suggests that exons 2, 3, 4, and 5 ofXistare less important for XCI. These insights provide valuable knowledge about the functional mechanism ofXist.
Neural shape mediation analysis
Authors: Brochard Jules , Combrisson Etienne , Chatard Benoit , Lachaux Jean-Philippe , Brovelli Andrea , Daunizeau Jean 
Published: September 2023

AbstractNeural signal shapes convey significant information about their generating processes. In this study, we introduce a data-driven methodology to identify sensory and behaviourally-relevant traces within neural responses. We present a phenomenological model that characterises temporal variations in intracranial EEG using eight interpretable parameters: peak time, peak intensity, initial and final baselines, accumulation and depletion period, and their respective concavities. This model effectively captures subtle signal variations, especially in sensory decision-making tasks. By decomposing the signals in this manner, we then conduct a comprehensive brain mediation analysis on iEEG data’s shape, pinpointing regions that mediate behavioural processes. Importantly, we can determine which signal dynamics specifically reflect underlying behavioural processes, enhancing the depth of analysis and critique of their role in behaviour. Preliminary applications on a cohort of epileptic patients reveal that our model explains over a third of the signal variance at the trial level across all brain regions. We identified four key regions—encompassing sensory, associative, frontal, and premotor areas—that mediate the impact of task difficulty on reaction time. Notably, in these regions, it was the depletion period, rather than signal amplitude, that correlated with behavioural speed. This study highlights the potential of our approach in providing detailed insights into the neural mechanisms linking stimuli to behaviour.
A reference genome and its epigenetic landscape of potentialOrychophragmus violaceus, an industrial crop species
Authors: Jia Changfu , Hou Yukang , Lai Qiang , Zhang Yuling , Wang Rui , Liu Jianquan , Wang Jing 
Published: September 2023

AbstractOrychophragmus violaceus, also called ‘er-yue-lan’ in China, is an annual plant of the family of Brassicaceae. The seed oil ofO. violaceuscontained two specific di-hydroxy fatty acids which were produced by functional divergence between twoFAD2WGD copies determine its industrial property. Here, we assembled a high-quality chromosome-level genome ofO. violaceusvia based on PacBio CLR technology and its cis-regulatory landscape of five mature tissues, including root, leaf, flower, seed and stem, based on ATAC-seq technology. 1.2 Gb draft genomic sequences were anchored to 12 pseudo-chromosomes and 49904 protein-coding genes were annotated on these chromosomes. To fully understand the epigenetic landscape ofO. violaceus, we further performed WGBS-seq for leaf, flower and silique tissues. In total, our multi-omics data provide opportunity to find out the differences between two WGD copies and also a valuable resource for downstream breeding effort of this potential industrial species.
Systematic identification of inter-chromosomal interaction networks supports the existence of RNA factories
Authors: Hristov Borislav Hrisimirov , Noble William Stafford , Bertero Alessandro 
Published: September 2023

AbstractMost studies of genome organization have focused on intra-chromosomal (cis) contacts because they harbor key features such as DNA loops and topologically associating domains. Inter-chromosomal (trans) contacts have received much less attention, and tools for interrogating potential biologically relevanttransstructures are lacking. Here, we develop a computational framework to identify sets of loci that jointly interact intransfrom Hi-C data. This method, trans-C, initiates probabilistic random walks with restarts from a set of seed loci to traverse an input Hi-C contact network, thereby identifying sets oftrans-contacting loci. We validate trans-C in three increasingly complex models of establishedtranscontacts: thePlasmodium falciparum vargenes, the mouse olfactory receptor “Greek islands”, and the human RBM20 cardiac splicing factory. We then apply trans-C to systematically test the hypothesis that genes co-regulated by the sametrans-acting element (i.e., a transcription or splicing factor) co-localize in three dimensions to form “RNA factories” that maximize the efficiency and accuracy of RNA biogenesis. We find that many loci with multiple binding sites of the same transcription factor interact with one another intrans, especially those bound by transcription factors with intrinsically disordered domains. Similarly, clustered binding of a subset of RNA binding proteins correlates withtransinteraction of the encoding loci. These findings support the existence oftransinteracting chromatin domains (TIDs) driven by RNA biogenesis. Trans-C provides an efficient computational framework for studying these and other types oftransinteractions, empowering studies of a poorly understood aspect of genome architecture.
Bypassing spike sorting: Density-based decoding using spike localization from dense multielectrode probes
Authors: Zhang Yizi , He Tianxiao , Boussard Julien , Windolf Charlie , Winter Olivier , Trautmann Eric , Roth Noam , Barrell Hailey , Churchland Mark , Steinmetz Nicholas A. ,   The International Brain Laboratory, Varol Erdem , Hurwitz Cole , Paninski Liam 
Published: September 2023

AbstractNeural decoding and its applications to brain computer interfaces (BCI) are essential for understanding the association between neural activity and behavior. A prerequisite for many decoding approaches isspike sorting, the assignment of action potentials (spikes) to individual neurons. Current spike sorting algorithms, however, can be inaccurate and do not properly model uncertainty of spike assignments, therefore discarding information that could potentially improve decoding performance. Recent advances in high-density probes (e.g., Neuropixels) and computational methods now allow for extracting a rich set of spike features from unsorted data; these features can in turn be used to directly decode behavioral correlates. To this end, we propose a spike sorting-free decoding method that directly models the distribution of extracted spike features using a mixture of Gaussians (MoG) encoding the uncertainty of spike assignments, without aiming to solve the spike clustering problem explicitly. We allow the mixing proportion of the MoG to change over time in response to the behavior and develop variational inference methods to fit the resulting model and to perform decoding. We benchmark our method with an extensive suite of recordings from different animals and probe geometries, demonstrating that our proposed decoder can consistently outperform current methods based on thresholding (i.e. multi-unit activity) and spike sorting. Open source code is available athttps://github.com/yzhang511/density_decoding.
Sex differences in offspring risk and resilience following 11β-hydroxylase antagonism in a rodent model of maternal immune activation
Authors: Martz Julia , Shelton Micah A. , Geist Laurel , Seney Marianne L. , Kentner Amanda C. 
Published: September 2023

AbstractMaternal immune activation (MIA) puts offspring at greater risk for neurodevelopmental disorders associated with impaired social behavior. While it is known that immune signaling through maternal, placental, and fetal compartments contributes to these phenotypical changes, it is unknown to what extent the stress response to illness is involved and how it can be harnessed for potential interventions. To this end, on gestational day 15, pregnant rat dams were administered the bacterial mimetic lipopolysaccharide (LPS; to induce MIA) alongside metyrapone, a clinically available 11β-hydroxylase inhibitor used to treat hypercortisolism in pregnant and neonatal populations. Maternal, placental, and fetal CNS levels of corticosterone and placental 11βHSD enzymes type 1 and 2 were measured 3-hrs post treatment. Offspring social behaviors were evaluated across critical phases of development. MIA was associated with increased maternal, placental, and fetal CNS corticosterone concentrations that were diminished with metyrapone exposure. Metyrapone protected against reductions in placental 11βHSD2 in males only, suggesting that less corticosterone was inactivated in female placentas. Behaviorally, metyrapone-exposure attenuated MIA-induced social disruptions in juvenile, adolescent, and adult males, while females were unaffected or performed worse. Metyrapone-exposure reversed MIA-induced transcriptional changes in monoamine-, glutamate-, and GABA-related genes in the ventral hippocampus of adult males, but not females. Taken together, these findings illustrate that MIA-induced HPA responses act alongside the immune system to produce behavioral deficits. As a clinically available drug, the sex-specific benefits and constraints of metyrapone should be investigated further as a potential means of reducing neurodevelopmental risks due to gestational MIA.