bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term effects of network-based fMRI neurofeedback training for sustained attention
Authors: Pamplona Gustavo Santo Pedro , Heldner Jennifer , Langner Robert , Koush Yury , Michels Lars , Ionta Silvio , Garrido Salmon Carlos Ernesto , Scharnowski Frank 
Published: October 2021

ABSTRACTNeurofeedback allows for learning voluntary control over one’s own brain activity, aiming to enhance cognition and clinical symptoms. A recent study improved sustained attention temporarily by training healthy participants to up-regulate the differential activity of the sustained attention network (SAN) minus the default mode network (DMN). However, long-term learning effects of functional magnetic resonance imaging (fMRI) neurofeedback training remain under-explored. Here, we evaluate the effects of network-based fMRI neurofeedback training for sustained attention by assessing behavioral and brain measures before, one day after, and two months after training. The behavioral measures include task as well as questionnaire scores, and the brain measures include activity and connectivity during self-regulation runs without feedback (i.e., transfer runs) and during resting-state runs. Neurally, we found that participants maintained their ability to control the differential activity during follow-up sessions. Further, exploratory analyses showed that the training-induced increase in FC between the DMN and occipital gyrus was maintained during follow-up transfer runs, but not during follow-up resting-state runs. Behaviorally, we found that enhanced sustained attention right after training returned to baseline level during follow-up. The discrepancy between lasting regulation-related brain changes but transient behavioral and resting-state effects raises the question of how neural changes induced by neurofeedback training translate to potential behavioral improvements. Since neurofeedback directly targets brain measures to indirectly improve behavior long-term, a better understanding of the brain-behavior associations during and after neurofeedback training is needed to develop its full potential as a promising scientific and clinical tool.Key pointsParticipants were still able to self-regulate the differential activity between large-scale networks two months after the end of neurofeedback training and this during transfer runs without feedback.Lasting brain changes were also observed in the functional connectivity of trained regions in runs during which participants engaged in active self-regulation as well as during resting-state runs without concomitant self-regulation.The increased sustained attention we observed right after the end of neurofeedback training did not persist two months later.
Left angular gyrus disconnection impairs multiplication fact retrieval
Authors: Smaczny S. , Sperber C. , Jung S. , Moeller K. , Karnath H.-O. , Klein E. 
Published: October 2021

AbstractArithmetic fact retrieval has been suggested to recruit a left-lateralized network comprising perisylvian language areas, parietal areas such as the angular gyrus (AG), and subcortical structures such as the hippocampus. However, the underlying white matter connectivity of these areas has not been evaluated systematically so far.Using simple multiplication problems, we evaluated how disconnections in parietal brain areas affected arithmetic fact retrieval following stroke. We derived disconnectivity measures by jointly considering data from n=73 patients with acute unilateral lesions in either hemisphere and a white-matter tractography atlas (HCP-842) using the Lesion Quantification Toolbox (LQT). Whole-brain voxel-based analysis indicated a left-hemispheric cluster of white matter fibers connecting the AG and superior temporal areas to be associated with a fact retrieval deficit. Subsequent analyses of direct grey-to-grey matter disconnections revealed that disconnections of additional left-hemispheric areas (e.g., between the superior temporal gyrus and parietal areas) were significantly associated with the observed fact retrieval deficit.Results imply that disconnections of parietal areas (i.e., the AG) with language-related areas (i.e., superior and middle temporal gyri) seem specifically detrimental to arithmetic fact retrieval. This suggests that arithmetic fact retrieval recruits a widespread left-hemispheric network and emphasizes the relevance of white matter connectivity for number processing.
Peripheral NOD-like receptor deficient inflammatory macrophages trigger neutrophil infiltration disrupting daytime locomotion
Authors: Kwon Victoria , Cai Peiwen , Dixon Cameron T. , Hamlin Victoria , Spencer Caroline G. , Rojas Alison M. , Shiau Celia E. 
Published: October 2021

AbstractInflammation is known to disrupt normal behavior, yet the underlying neuroimmune interactions remain elusive. Here, we investigated whether inappropriate macrophage-evoked inflammation alters CNS control of daily-life animal locomotion using a set of zebrafish mutants selected for specific macrophage dysfunction and microglia deficiency. Large-scale genetic and computational analyses revealed that NOD-like receptornlrc3lmutants are capable of normal motility and visuomotor response, but preferentially swim less in the daytime, suggesting low motivation rather than physical impairment. Examining their brain activities and structures implicate impaired dopaminergic descending circuits, where neutrophils abnormally infiltrate. Furthermore, neutrophil depletion recovered daytime locomotion. Restoring wild-type macrophages reversed behavioral and neutrophil aberrations, while three other microglia-lacking mutants failed to phenocopynlrc3lmutants. Overall, we reveal how peripheral inflammatory macrophages with elevated pro-inflammatory cues (includingil1b,tnfa,cxcl8a) in the absence of microglia co-opt neutrophils to infiltrate the brain, thereby enabling local modulation of neural circuits affecting spontaneous locomotion.
DNA-dependent binding of nargenicin to DnaE1 inhibits replication in Mycobacterium tuberculosis
Authors: Chengalroyen Melissa D. , Mason Mandy K. , Borsellini Alessandro , Tassoni Raffaella , Abrahams Garth L. , Lynch Sasha , Ahn Yong-Mo , Ambler Jon , Young Katherine , Crowley Brendan M. , Olsen David B. , Warner Digby F. , Barry Clifton E. , Boshoff Helena I.M. , Lamers Meindert H. , Mizrahi Valerie 
Published: October 2021

SUMMARYNatural products provide a rich source of potential antimicrobials for use in treating infectious diseases for which drug resistance has emerged. Foremost among these is tuberculosis. Assessment of the antimycobacterial activity of nargenicin, a natural product that targets the replicative DNA polymerase of Staphylococcus aureus, revealed that it is a bactericidal genotoxin that induces a DNA damage response in Mycobacterium tuberculosis (Mtb) and inhibits growth by blocking the replicative DNA polymerase, DnaE1. Cryo-electron microscopy revealed that binding of nargenicin to Mtb DnaE1 requires the DNA substrate such that nargenicin is wedged between the terminal base pair and the polymerase and occupies the position of both the incoming nucleotide and templating base. Comparative analysis across three bacterial species suggests that the activity of nargenicin is partly attributable to the DNA binding affinity of the replicative polymerase. This work has laid the foundation for target-led drug discovery efforts focused on Mtb DnaE1.
SpatialDE2: Fast and localized variance component analysis of spatial transcriptomics
Authors: Kats Ilia , Vento-Tormo Roser , Stegle Oliver 
Published: October 2021

AbstractSpatial transcriptomics is now a mature technology, allowing to assay gene expression changes in the histological context of complex tissues. A canonical analysis workflow starts with the identification of tissue zones that share similar expression profiles, followed by the detection of highly variable or spatially variable genes. Rapid increases in the scale and complexity of spatial transcriptomic datasets demand that these analysis steps are conducted in a consistent and integrated manner, a requirement that is not met by current methods. To address this, we here present SpatialDE2, which unifies the mapping of tissue zones and spatial variable gene detection as integrated software framework, while at the same time advancing current algorithms for both of these steps. Formulated in a Bayesian framework, the model accounts for the Poisson count noise, while simultaneously offering superior computational speed compared to previous methods. We validate SpatialDE2 using simulated data and illustrate its utility in the context of two real-world applications to the spatial transcriptomics profiles of the mouse brain and human endometrium.
Using the UK Biobank as a global reference of worldwide populations: application to measuring ancestry diversity from GWAS summary statistics
Authors: Privé Florian 
Published: October 2021

AbstractMotivationMeasuring genetic diversity is an important problem because increasing genetic diversity is key to making new genetic discoveries, while also being a major source of confounding to be aware of in genetics studies.ResultsUsing the UK Biobank data, a prospective cohort study with deep genetic and phenotypic data collected on almost 500,000 individuals from across the United Kingdom, we carefully define 21 distinct ancestry groups from all four corners of the world. These ancestry groups can serve as a global reference of worldwide populations, with a handful of applications. Here we develop a method that uses allele frequencies and principal components derived from these ancestry groups to effectively measure ancestry proportions from allele frequencies of any genetic dataset.AvailabilityThis method is implemented as function snp_ancestry_summary as part of R package bigsnpr.Contactflorian.prive.21@gmail.com
Structural and functional characterization of DdrC, a novel DNA damage-induced nucleoid associated protein involved in DNA compaction
Authors: Banneville Anne-Sophie , de la Tour Claire Bouthier , Hognon Cécilia , Colletier Jacques-Philippe , Teulon Jean-Marie , Le Roy Aline , Pellequer Jean-Luc , Monari Antonio , Dehez François , Confalonieri Fabrice , Servant Pascale , Timmins Joanna 
Published: October 2021

ABSTRACTDeinococcus radiodurans is a spherical bacterium well-known for its outstanding resistance to DNA-damaging agents. Exposure to such agents leads to drastic changes in the transcriptome of D. radiodurans. In particular, four Deinococcus-specific genes, known as DNA Damage Response genes, are strongly up-regulated and have been shown to contribute to the resistance phenotype of D. radiodurans. One of these, DdrC, is expressed shortly after exposure to γ-radiation and is rapidly recruited to the nucleoid. In vitro, DdrC has been shown to compact circular DNA, circularize linear DNA, anneal complementary DNA strands and protect DNA from nucleases. To shed light on the possible functions of DdrC in D. radiodurans, we determined the crystal structure of the domain-swapped DdrC dimer at a resolution of 2.2 Å and further characterized its DNA binding and compaction properties. Notably, we show that DdrC bears two asymmetric DNA binding sites located on either side of the dimer and can modulate the topology and level of compaction of circular DNA. These findings suggest that DdrC may be a DNA damage-induced nucleoid-associated protein that enhances nucleoid compaction to limit the dispersion of the fragmented genome and facilitate DNA repair after exposure to severe DNA damaging conditions.
TEMPO: A system to sequentially label and genetically manipulate vertebrate cell lineages
Authors: Espinosa-Medina Isabel , Feliciano Daniel , Belmonte-Mateos Carla , Garcia-Marques Jorge , Foster Benjamin , Miyares Rosa Linda , Pujades Cristina , Koyama Minoru , Lee Tzumin 
Published: October 2021

AbstractDuring development, regulatory factors appear in a precise order to determine cell fates over time. To investigate complex tissue development, one should not just label cell lineages but further visualize and manipulate cells with temporal control. Current strategies for tracing vertebrate cell lineages lack genetic access to sequentially produced cells. Here we present TEMPO (Temporal Encoding and Manipulation in a Predefined Order), an imaging-readable genetic tool allowing differential labelling and manipulation of consecutive cell generations in vertebrates. TEMPO is based on CRISPR and powered by a cascade of gRNAs that drive orderly activation/inactivation of reporters/effectors. Using TEMPO to visualize zebrafish and mouse neurogenesis, we recapitulated birth-order-dependent neuronal fates. Temporally manipulating cell-cycle regulators in mouse cortex progenitors altered the proportion and distribution of neurons and glia, revealing the effects of temporal gene perturbation on serial cell fates. Thus, TEMPO enables sequential manipulation of molecular factors, crucial to study cell-type specification.One-Sentence SummaryGaining sequential genetic access to vertebrate cell lineages.
Estimating the Inter- and Intra-Rater Reliability for NASH Fibrosis Staging in the Presence of Bridge Ordinal Ratings with Hierarchical Bridge Category Models
Authors: Levy Joshua , Bobak Carly , Azizgolshani Nasim , Liu Xiaoying , Ren Bing , Lisovsky Mikhail , Suriawinata Arief , Christensen Brock , O’Malley James , Vaickus Louis 
Published: October 2021

AbstractThe public health burden of non-alcoholic steatohepatitis (NASH), a liver condition characterized by excessive lipid accumulation and subsequent tissue inflammation and fibrosis, has burgeoned with the spread of western lifestyle habits. Progression of fibrosis into cirrhosis is assessed using histological staging scales (e.g., NASH Clinical Research Network (NASH CRN)). These scales are used to monitor disease progression as well as to evaluate the effectiveness of therapies. However, clinical drug trials for NASH are typically underpowered due to lower than expected inter-/intra-rater reliability, which impacts measurements at screening, baseline, and endpoint. Bridge ratings represent a phenomenon where pathologists assign two adjacent stages simultaneously during assessment and may further complicate these analyses when ad hoc procedures are applied. Statistical techniques, dubbed Bridge Category Models, have been developed to account for bridge ratings, but not for the scenario where multiple pathologists assess biopsies across time points. Here, we develop hierarchical Bayesian extensions for these statistical methods to account for repeat observations and use these methods to assess the impact of bridge ratings on the inter-/intra-rater reliability of the NASH CRN staging scale. We also report on how pathologists may differ in their assignment of bridge ratings to highlight different staging practices. Our findings suggest that Bridge Category Models can capture additional fibrosis staging heterogeneity with greater precision, which translates to potentially higher reliability estimates in contrast to the information lost through ad hoc approaches.
Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response
Authors: Chowdhary Surabhi , Kainth Amoldeep S. , Paracha Sarah , Gross David S. , Pincus David 
Published: October 2021

SUMMARYMammalian developmental and disease-associated genes concentrate large quantities of the transcriptional machinery by forming membrane-less compartments known as transcriptional condensates. However, it is unknown whether these structures are evolutionarily conserved, capable of stress-inducible gene activation or involved in 3D genome reorganization. Here, we identify inducible transcriptional condensates in the yeast heat shock response (HSR). HSR condensates are biophysically dynamic spatiotemporal clusters of the sequence-specific transcription factor Heat shock factor 1 (Hsf1) with Mediator and RNA Pol II. Uniquely, HSR condensates drive the coalescence of multiple Hsf1 target genes, even those located on different chromosomes. Binding of the chaperone Hsp70 to a site on Hsf1 represses clustering, while an intrinsically disordered region on Hsf1 promotes condensate formation and intergenic interactions. Mutation of both Hsf1 determinants reprograms HSR condensates to become mammalian-like: constitutively active without intergenic coalescence. These results suggest that transcriptional condensates are ancient and flexible compartments of eukaryotic gene control.
A BERT-Based Hybrid System for Chemical Identification and Indexing in Full-Text Articles
Authors: Erdengasileng Arslan , Li Keqiao , Han Qing , Tian Shubo , Wang Jian , Hu Ting , Zhang Jinfeng 
Published: October 2021

AbstractIdentification and indexing of chemical compounds in full-text articles are essential steps in biomedical article categorization, information extraction, and biological text mining. BioCreative Challenge was established to evaluate methods for biological text mining and information extraction. Track 2 of BioCreative VII (summer 2021) consists of two subtasks: chemical identification and chemical indexing in full-text PubMed articles. The chemical identification subtask also includes two parts: chemical named entity recognition (NER) and chemical normalization. In this paper, we present our work on developing a hybrid pipeline for chemical named entity recognition, chemical normalization, and chemical indexing in full-text PubMed articles. Specifically, we applied BERT-based methods for chemical NER and chemical indexing, and a sieve-based dictionary matching method for chemical normalization. For subtask 1, we used PubMedBERT with data augmentation on the chemical NER task. Several chemical-MeSH dictionaries including MeSH.XML, SUPP.XML, MRCONSO.RFF, and PubTator chemical annotations are used in a specific order to get the best performance on chemical normalization. We achieved an F1 score of 0.86 and 0.7668 on chemical NER and chemical normalization, respectively. For subtask 2, we formulated it as a binary prediction problem for each individual chemical compound name. We then used a BERT-based model with engineered features and achieved a strict F1 score of 0.4825 on the test set, which is substantially higher than the median F1 score (0.3971) of all the submissions.
Offline memory replay in recurrent neuronal networks emerges from constraints on online dynamics
Authors: Milstein Aaron D. , Tran Sarah , Ng Grace , Soltesz Ivan 
Published: October 2021

AbstractDuring spatial exploration, neural circuits in the hippocampus store memories of sequences of sensory events encountered in the environment. When sensory information is absent during “offline” resting periods, brief neuronal population bursts can “replay” sequences of activity that resemble bouts of sensory experience. These sequences can occur in either forward or reverse order, and can even include spatial trajectories that have not been experienced, but are consistent with the topology of the environment. The neural circuit mechanisms underlying this variable and flexible sequence generation are unknown. Here we demonstrate in a recurrent spiking network model of hippocampal area CA3 that experimental constraints on network dynamics such as population sparsity, stimulus selectivity, rhythmicity, and spike rate adaptation enable additional emergent properties, including variable offline memory replay. In an online stimulus-driven state, we observed the emergence of neuronal sequences that swept from representations of past to future stimuli on the timescale of the theta rhythm. In an offline state driven only by noise, the network generated both forward and reverse neuronal sequences, and recapitulated the experimental observation that offline memory replay events tend to include salient locations like the site of a reward. These results demonstrate that biological constraints on the dynamics of recurrent neural circuits are sufficient to enable memories of sensory events stored in the strengths of synaptic connections to be flexibly read out during rest and sleep, which is thought to be important for memory consolidation and planning of future behavior.
Presence of Toxoplasma gondii tissue cysts in human semen
Authors: Tong Wen Han , Hlaváčová Jana , Abdulai-Saiku Samira , Kaňková Šárka , Flegr Jaroslav , Vyas Ajai 
Published: October 2021

AbstractToxoplasma gondii is a widely prevalent protozoan parasite in human populations. This parasite is thought to be primarily transmitted through undercooked meat and contamination by cat feces. Here, we demonstrate that Toxoplasma gondii cysts can be found within human semen, thus suggesting a potential for sexual transmission. We visualized Toxoplasma gondii cysts in ejaculates of immune-competent and latently infected human volunteers. We confirmed the encystment by probing transcription of a bradyzoite-specific gene in these structures. These observations extend previous observations of the parasite in semen of several non-human host species, including rats, dogs, and sheep. Toxoplasma gondii infection is a clinically significant infection, in view of its high prevalence, its purported role in neuropsychiatric disorders such as schizophrenia, as well as in the more serious form of congenital toxoplasmosis. Our demonstration of intact Toxoplasma gondii cysts in the ejaculate supports the possibility of sexual transmission of the parasite and provides an impetus for further investigations.ImportanceToxoplasma gondii is recognized as one of the five infections that can harm fetal health. There is also emerging evidence that toxoplasmosis is related to the development of neuropsychiatric disorders. In this context, the current report includes visual evidence of Toxoplasma gondii cyst presence in the semen of human males. It is thus plausible that this clinically significant infection can be sexually transmitted. The existence of sexual transmission in a population, and its relative importance vis-à-vis other transmission routes, remains undetermined. These possibilities are of acute relevance to human health in the context of sexual health and pregnancy management.