bluuebunny/crossref_metadata_2025_split huggingface dataset:
Task-specific neural processes underlying conflict resolution during cognitive control
Authors: Xiao Yuchen , Chou Chien-Chen , Cosgrove Garth Rees , Crone Nathan E , Stone Scellig , Madsen Joseph R , Reucroft Ian , Shih Yen-Cheng , Weisholtz Daniel , Yu Hsiang-Yu , Anderson William S. , Kreiman Gabriel 
Published: January 2022

AbstractCognitive control involves flexibly combining multiple sensory inputs with task-dependent goals during decision making. Several tasks have been proposed to examine cognitive control, including Stroop, Eriksen-Flanker, and the Multi-source interference task. Because these tasks have been studied independently, it remains unclear whether the neural signatures of cognitive control reflect abstract control mechanisms or specific combinations of sensory and behavioral aspects of each task. To address this question, here we recorded invasive neurophysiological signals from 16 subjects and directly compared the three tasks against each other. Neural activity patterns in the theta and high-gamma frequency bands differed between incongruent and congruent conditions, revealing strong modulation by conflicting task demands. These neural signals were specific to each task, generalizing within a task but not across tasks. These results highlight the complex interplay between sensory inputs, motor outputs, and task demands and argue against a universal and abstract representation of conflict.
Using strain-resolved analysis to identify contamination in metagenomics data
Authors: Lou Yue Clare , Hoff Jordan , Olm Matthew R. , West-Roberts Jacob , Diamond Spencer , Firek Brian A. , Morowitz Michael J. , Banfield Jillian F. 
Published: January 2022

AbstractMetagenomics analyses can be negatively impacted by DNA contamination. While external sources of contamination such as DNA extraction kits have been widely reported and investigated, contamination originating within the study itself remains underreported. Here we applied high-resolution strain-resolved analyses to identify contamination in two large-scale clinical metagenomics datasets. By mapping strain sharing to DNA extraction plates, we identified well-to-well contamination in both negative controls and biological samples in one dataset. Such contamination is more likely to occur among samples that are on the same or adjacent columns or rows of the extraction plate than samples that are far apart. Our strain-resolved workflow also reveals the presence of externally derived contamination, primarily in the other dataset. Overall in both datasets, contamination is more significant in samples with lower biomass. Our work demonstrates that genome-resolved strain tracking, with its essentially genome-wide nucleotide-level resolution, can be used to detect contamination in sequencing-based microbiome studies. Our results underscore the value of strain-specific methods to detect contamination and the critical importance of looking for contamination beyond negative and positive controls.
Criticality and network structure drive emergent oscillations in a stochastic whole-brain model
Authors: Barzon Giacomo , Nicoletti Giorgio , Mariani Benedetta , Formentin Marco , Suweis Samir 
Published: January 2022

AbstractUnderstanding the relation between the structure of brain networks and its functions is a fundamental open question. Simple models of neural activity based on real anatomical networks have proven to be effective in describing features of whole-brain spontaneous activity when tuned at their critical point. In this work, we show that indeed structural networks are a crucial ingredient in the emergence of collective oscillations in a whole-brain stochastic model at criticality. We study analytically a stochastic Greenberg-Hastings cellular automaton in the mean-field limit, showing that it undergoes an abrupt phase transition with a bistable region. In particular, no global oscillations emerge in this limit. Then, we show that by introducing a network structure in the homeostatic normalization regime, the bistability may be disrupted, and the transition may become smooth. Concomitantly, through an interplay between the network topology and weights, a large peak in the power spectrum appears around the transition point, signaling the emergence of collective oscillations. Hence, both the structure of brain networks and criticality are fundamental in driving the collective responses of whole-brain stochastic models.
piggyBac-Mediated Genomic Integration of Linear dsDNA-Based Library for Deep Mutational Scanning in Mammalian Cells
Authors: Wang Yi , Zhao Yanjie , Li Yifan , Zhang Kaili , Fan Yan , Su Weijun , Li Shuai 
Published: January 2022

AbstractDeep mutational scanning (DMS) makes it possible to perform massively parallel quantification of the relationship between genetic variants and phenotypes of interest. However, the difficulties in introducing large variant libraries into mammalian cells greatly hinder DMS under physiological states. Here we developed two novel strategies for DMS library construction in mammalian cells, namely ‘piggyBac-in-vitroligation’ and ‘piggyBac-in-vitroligation-PCR’. For the first strategy, we took the ‘in-vitroligation’ approach to prepare high-diversity linear dsDNAs, and integrate them into the mammalian genome with a piggyBac transposon system. For the second strategy, we further added a PCR step using thein-vitroligation dsDNAs as templates, for the construction of high-content genome-integrated libraries via large-scale transfection. Both strategies could successfully establish genome-integrated EGFP-chromophore randomized libraries in HEK293T cells and enrich the green fluorescence-chromophore amino acid sequences. And we further identified a novel transcriptional activator peptide with the ‘piggyBac-in-vitroligation-PCR’ strategy. Our novel strategies greatly facilitate the construction of large variant DMS library in mammalian cells, and may have great application potential in the future.
The central role of the interspecific interactions in the evolution of microbial communities
Authors: Raynaud Tiffany , Blouin Manuel , Devers-Lamrani Marion , Garmyn Dominique , Spor Aymé 
Published: January 2022

ABSTRACTThe interspecific interactions play an important role in the establishment of a community phenotype. Furthermore, the evolution of a community can not only occur through an evolution of the species composing the community but also of the interactions among them. In this study, we investigated how widespread was the evolution of interspecific interactions in the evolutionary response of eight two-bacterial species communities regarding productivity. We found evidence for an evolution of the interactions in half of the studied communities which gave rise to a mean change of 15% in community productivity as compared to what was expected from the individual responses. Even when the interactions did not evolve themselves, they influenced the evolutionary responses of the bacterial strains within the communities which further affected community response. We found that the evolution within a community often promoted an adaptation of the bacterial strains to the abiotic environment, especially for the dominant strain in a community. Overall, this study suggested that the evolution of the interspecific interactions was frequent and that it could increase community response to evolution. We propose that the existence of an evolution of the interspecific interactions can justify the consideration of the community as a unit of selection.
Mucosal associated invariant T cells are altered in patients with Hidradenitis Suppurativa and contribute to the inflammatory milieu
Authors: Gallagher Catriona , Mahon Julie Mac , O’Neill Chloe , Cassidy Féaron C. , Dunbar Hazel , De Barra Conor , Cadden Caoimhe , Pisarska Marta M. , Wood Nicole , Masterson Joanne C. , McNamee Eoin N. , English Karen , O’Shea Donal , Tobin Anne Marie , Hogan Andrew E. 
Published: January 2022

AbstractMucosal Associated Invariant T cells are a population of “innate” T cells, which express the invariant T cell receptor (TCR) α chain Vα 7.2-Jα 33 and are capable of robust rapid cytokine secretion, producing a milieu of cytokines including IFN-γ and IL-17. MAIT cells have been reported in multiple human tissues including the gut, periphery and skin. On-going research has highlighted their involvement in numerous inflammatory diseases ranging from rheumatoid arthritis and obesity to psoriasis. Hidradenitis Suppurativa (H.S) is a chronic inflammatory disease of the hair follicles, resulting in painful lesions of apocrine-bearing skin. Several inflammatory cytokines have been implicated in the pathogenesis of H.S including IL-17. The role of MAIT cells in H.S is currently unknown. In this study we show for the first time, that MAIT cells are altered in the peripheral blood of patients with H.S, with reduced frequencies and an IL-17 cytokine bias. We show that CCL20 expression is elevated in lesions of patients with H.S, and MAIT cells can actively traffic towards lesions via CCL20. We show that MAIT cells can accumulate in the lesions from patients with H.S. when compared to adjacent skin, with an IL-17 bias. We show that elevated IL-17, can be linked to the activation of dermal fibroblasts, promoting the expression of chemotactic signals including CCL20 and CXCL1. Finally, we show that targeting the IL-17A transcription factor RORyt robustly reduces IL-17 production by MAIT cells from patients with H.S. Collectively our data details IL-17 producing MAIT cells as a novel player in the pathogenesis of H.S and highlights the potential of RORyt inhibition as a novel therapeutic strategy.
Cell morphological profiling enables high-throughput screening for PROteolysis TArgeting Chimera (PROTAC) phenotypic signature
Authors: Trapotsi Maria-Anna , Mouchet Elizabeth , Williams Guy , Monteverde Tiziana , Juhani Karolina , Turkki Riku , Miljković Filip , Martinsson Anton , Mervin Lewis , Müllers Erik , Barrett Ian , Engkvist Ola , Bender Andreas , Moreau Kevin 
Published: January 2022

SummaryPROTACs (PROteolysis TArgeting Chimeras) use the ubiquitin-proteasome system to degrade a protein of interest for therapeutic benefit. Advances in targeted protein degradation technology have been remarkable with several molecules moving into clinical studies. However, robust routes to assess and better understand the safety risks of PROTACs need to be identified, which is an essential step towards delivering efficacious and safe compounds to patients. In this work, we used Cell Painting, an unbiased high content imaging method, to identify phenotypic signatures of PROTACs. Chemical clustering and model prediction allowed the identification of a mitotoxicity signature that could not be expected by screening the individual PROTAC components. The data highlighted the benefit of unbiased phenotypic methods for identifying toxic signatures and the potential to impact drug design.HighlightsMorphological profiling detects various PROTACs’ phenotypic signaturesPhenotypic signatures can be attributed to diverse biological responsesChemical clustering from phenotypic signatures separates on drug selectionTrained in-silico machine learning models to predict PROTACs’ mitochondrial toxicity
HITS-CLIP analysis of human ALKBH8 points towards its role in tRNA and noncoding RNA regulation
Authors: Cavallin Ivana , Bartošovič Marek , Skalický Tomas , Rengaraj Praveenkumar , Schmidt-Dengler Martina Christina , Drino Aleksej , Helm Mark , Vaňáčová Štěpánka 
Published: January 2022

AbstractTransfer RNAs acquire a large plethora of chemical modifications. Among those, modifications of the anticodon loop play important roles in translational fidelity and tRNA stability. Four human wobble U containing tRNAs obtain 5-methoxycarbonylmethyluridine (mcm5U34) or 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U34), which play a role in decoding. This mark involves a cascade of enzymatic activities. The last step is mediated by Alkylation Repair Homolog 8 (ALKBH8). In this study, we performed a transcriptome-wide analysis of the repertoire of ALKBH8 RNA targets. Using a combination of HITS-CLIP-seq and RIP-seq analyses, we uncover ALKBH8-bound RNAs. It targets an additional wobble U-containing tRNA tRNALys(UUU). More interestingly, the spectrum of bound RNAs includes other types of non-coding RNAs, such as C/D box snoRNAs, 7SK RNA or some miRNAs, respectively.
Basis of narrow-spectrum activity of fidaxomicin on gut pathogen Clostridioides difficile
Authors: Cao Xinyun , Boyaci Hande , Chen James , Bao Yu , Landick Robert , Campbell Elizabeth A. 
Published: January 2022

AbstractFidaxomicin (Fdx) is widely used to treat Clostridioides difficile (Cdiff) infections (CDIs), but the molecular basis of its narrow-spectrum activity in the human gut microbiome remains enigmatic. CDIs are a leading cause of nosocomial deaths. Fdx, which inhibits RNA polymerase (RNAP), targets Cdiff with minimal effects on gut commensals, reducing CDI recurrence. Here, we present the cryo-electron microscopy structure of Cdiff RNAP in complex with Fdx, allowing us to identify a crucial Fdx-binding determinant of Cdiff RNAP that is absent in most gut microbiota like Proteobacteria and Bacteroidetes. By combining structural, biochemical, and bioinformatic analyses, we establish that a single RNAP residue is a sensitizing element for Fdx narrow-spectrum activity. Our results provide a blueprint for targeted drug design against an important human pathogen.
Quantitative Models of Lipid Transfer and Membrane Contact Formation
Authors: Zhang Yongli , Ge Jinghua , Bian Xin , Kumar Avinash 
Published: January 2022

AbstractLipid transfer proteins (LTPs) transport lipids between different organelles in the cell, and thus play key roles in lipid homeostasis and organelle dynamics. The lipid transfer process often occurs at the membrane contact sites (MCS), where two membranes are held within 10-30 nm by LTPs and other membrane tethering factors. While most LTPs act as a shuttle to transfer lipids via their lipid-binding cavities, recent experiments reveal a new category of eukaryotic LTPs that may serve as a bridge to transport lipids in bulk at MCSs, leading to membrane expansion involved in organelle biogenesis. However, the molecular mechanisms underlying lipid transfer and membrane contact formation are not well understood. Here, we first review two recent studies of extended synaptotagmin (E-Syt)-mediated membrane binding and lipid transfer using optical tweezers and DNA origami, respectively. Then we describe mathematical models to quantify the kinetics of lipid transfer by shuttle LTPs based on a lipid exchange mechanism. We find that simple lipid mixing among similar membranes and/or lipid partitioning among different membranes can explain lipid transfer against a concentration gradient widely observed for LTPs. Based on these calculations, we hypothesize that lipid exchange is a general mechanism for lipid transfer by shuttle LTPs. We predict that selective transport of lipids, but not membrane proteins, by bridge LTPs leads to osmotic membrane tension in analog to the osmotic pressure across a semipermeable membrane. A gradient of such osmotic membrane tension and the conventional membrane tension may drive bulk lipid flow through bridge LTPs at a speed consistent with the fast membrane expansion observed in vivo. Finally, we discuss the implications of membrane tension and lipid transfer in organelle biogenesis and membrane morphologies. Overall, the quantitative models may help clarify the mechanisms of MCS formation by E-Syts and lipid transfer by LTPs in general.
Mucolytic bacteria license pathobionts to acquire host-derived nutrients during dietary nutrient restriction
Authors: Sugihara Kohei , Kitamoto Sho , Saraithong Prakaimuk , Nagao-Kitamoto Hiroko , McCarthy Caroline , Hoostal Matthew , Rosevelt Alexandra , Muraleedharan Chithra K , Gillilland Merritt G. , Imai Jin , Omi Maiko , Bishu Shrinivas , Kao John Y. , Alteri Christopher J. , Barnich Nicolas , Schmidt Thomas M. , Nusrat Asma , Inohara Naohiro , Golob Jonathan L. , Kamada Nobuhiko 
Published: January 2022

AbstractPathobionts employ unique metabolic adaptation mechanisms to maximize their growth in disease conditions. Adherent–invasive Escherichia coli (AIEC), a pathobiont enriched in the gut mucosa of patients with inflammatory bowel disease (IBD), utilizes diet-derived L-serine to adapt to the inflamed gut. Therefore, the restriction of dietary L-serine starves AIEC and limits its fitness advantage. Here, we find that AIEC can overcome this nutrient limitation by switching the nutrient source from the diet to the host cells in the presence of mucolytic bacteria. During diet-derived L-serine restriction, the mucolytic symbiont Akkermansia muciniphila promotes the encroachment of AIEC to the epithelial niche by degrading the mucus layer. In the epithelial niche, AIEC acquires L-serine from the colonic epithelium and thus proliferates. Our work suggests that the indirect metabolic network between pathobionts and commensal symbionts enables pathobionts to overcome nutritional restriction and thrive in the gut.
Development of efficient RNAi methods in the corn leafhopper Dalbulus maidis, a promising application for pest control
Authors: Dalaisón-Fuentes L.I. , Pascual A. , Gazza E. , Welchen E. , Rivera-Pomar R. , Catalano M.I. 
Published: January 2022

ABSTRACTBACKGROUNDThe corn leafhopper Dalbulus maidis is the main vector of three important stunting pathogens that affect maize production. The most common control strategy against this species is the use of insecticides that provide minimal, short-term protection. In this context, genomic-based technologies such as RNA interference (RNAi) could be a suitable approach to control this pest in a highly specific manner, avoiding the adverse effects associated with insecticide misuse. Therefore, the objective of the present work was to assess the application of RNAi on D. maidis through different dsRNA delivery methods and known the function of target gene, Bicaudal C (BicC).RESULTSWe have identified and characterized the core components of the RNAi machinery in silico and established two methods of exogenous double-stranded RNAs (dsRNA) delivery to D. maidis. BicC -an important regulator of insect oogenesis-dsRNA was successfully delivered via injection or ingestion to adult females, causing significant reductions in the transcript levels and ovipositions and observable phenotypes in the ovaries when compared to control females. The small doses of dsRNABicC administered were enough to trigger a strong RNAi response, demonstrating that D. maidis is highly sensitive to RNAi.CONCLUSIONThis is, to our knowledge, the first report describing RNAi application in D. maidis, a tool that can be used to advance towards a novel, insecticide-free control strategy against this pest.
Brainwide input-output architecture of paraventricular oxytocin and vasopressin neurons
Authors: Freda S.N. , Priest M.F. , Badong D. , Xiao L. , Liu Y. , Kozorovitskiy Y. 
Published: January 2022

SummaryOxytocin and vasopressin are pleiotropic neuropeptides with well-established roles in the regulation of social behavior and homeostatic functions. Their structural similarity and conserved functions in vertebrate social behavior suggest that neurohypophyseal peptides may represent a single integrative neuromodulatory system, yet both peptides subserve sexually dimorphic functions at the behavioral level. The extent to which central oxytocin and vasopressin systems share similar circuit architecture has not been previously studied. Sex differences in the central circuitry of the oxytocin and vasopressin systems may underlie sex-variant behaviors, but it is currently unknown whether the synaptic inputs or outputs of each neuropeptidergic system vary across males and females. To close this gap, we generated quantitative anterograde and retrograde maps of the paraventricular oxytocin and vasopressin systems in mice. We observed that both oxytocinergic and vasopressinergic neurons share highly similar synaptic inputs that are sex-conserved. Projection patterns differed across systems and showed sex differences, more pronounced in the vasopressin neurons. Together our data represent the first comparative study of oxytocin and vasopressin input-output architecture highlighting how these neurohypopheseal peptides can play complementary and overlapping roles that are sex-dependent.
The Streptococcus agalactiae R3 surface protein is encoded by sar5
Authors: Dragset Marte Singsås , Basson Adelle , Olaisen Camilla , Selvik Linn-Karina , Lyng Randi Valsø , Lysvand Hilde , Aas Christina Gabrielsen , Afset Jan Egil 
Published: January 2022

ABSTRACTStreptococcus agalactiae (a group B streptococcus; GBS) is an important human pathogen causing pneumonia, sepsis and meningitis in neonates, as well as infections in pregnant women, immunocompromised individuals, and the elderly. For the future control of GBS-inflicted disease, GBS surface exposed proteins are particularly relevant as they may act as antigens for vaccine development and/or as serosubtype markers in epidemiological settings. Even so, the genes encoding some of the surface proteins established as serosubtype markers by antibody-based methods are still unknown. Here, we identify sar5 as the gene encoding the R3 surface protein, a serosubtype marker of hitherto unknown genetic origin.
The voltage-gated Cav Ca2+ channel subunit α2δ-4 is required for locomotor behavior and sensorimotor gating in mice
Authors: Klomp Annette , Omichi Ryotaro , Iwasa Yoichiro , Smith Richard J. , Usachev Yuriy M. , Russo Andrew F. , Narayanan Nandakumar , Lee Amy 
Published: January 2022

AbstractVoltage-gated Cav Ca2+ channels are critical for the development and mature function of the nervous system. Variants in the CACNA2D4 gene encoding the α2δ-4 auxiliary subunit of these channels are associated with neuropsychiatric and neurodevelopmental disorders. α2δ-4 is prominently expressed in the retina and is crucial for vision, but extra-retinal functions of α2δ-4 have not been investigated. Here, we sought to fill this gap by analyzing the behavioral phenotypes of α2δ-4 knockout (KO) mice. α2δ-4 KO mice (both males and females) exhibited significant impairments in prepulse inhibition that were unlikely to result from the modestly elevated auditory brainstem response thresholds. Whereas α2δ-4 KO mice of both sexes were hyperactive in various assays, only females showed impaired motor learning/coordination in the rotarod assay. Female but not male α2δ-4 KO mice exhibited anxiolytic and anti-depressive behaviors in the elevated plus maze and tail suspension tests, respectively. Our results reveal an unexpected role for α2δ-4 in cognitive and motor function and identify α2δ-4 KO mice as a novel model for studying the pathophysiology associated with CACNA2D4 variants.