bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hi-TrAC reveals fractal nesting of super-enhancers
Authors: Cao Yaqiang , Liu Shuai , Cui Kairong , Tang Qingsong , Zhao Keji 
Published: July 2022

AbstractEukaryotic genome spatial folding plays a key role in genome function. Decoding the principles and dynamics of 3D genome organization depends on improving technologies to achieve higher resolution. Chromatin domains have been suggested as regulatory micro-environments, whose identification is crucial to understand the genome architecture. We report here that our recently developed method, Hi-TrAC, which specializes in detecting chromatin loops among genomic accessible regulatory regions, allows us to examine active domains with limited sequencing depths at a high resolution. Hi-TrAC can detect active sub-TADs with a median size of 100kb, most of which harbor one or two cell specifically expressed genes and regulatory elements such as super-enhancers organized into nested interaction domains. These active sub-TADs are characterized by highly enriched signals of histone mark H3K4me1 and chromatin-binding proteins, including Cohesin complex. We show that knocking down core subunit of the Cohesin complex using shRNAs in human cells or decreasing the H3K4me1 modification by deleting the H3K4 methyltransferase Mll4 gene in mouse Th17 cells disrupted the sub-TADs structure. In summary, Hi-TrAC serves as a compatible and highly responsive approach to studying dynamic changes of active sub-TADs, allowing us more explicit insights into delicate genome structures and functions.Highlights-Hi-TrAC detects active sub-TADs with a median size of 100 kb.-Hi-TrAC reveals a block-to-block interaction pattern between super-enhancers, and fractal structures within super-enhancers.-Active sub-TADs are disrupted by the knockdown of RAD21.-Active sub-TADs interaction densities are decreased by the knockout of Mll4.
A stable, distributed code for cue value in mouse cortex during reward learning
Authors: Ottenheimer David J. , Hjort Madelyn M. , Bowen Anna J. , Steinmetz Nicholas A. , Stuber Garret D. 
Published: July 2022

SummaryThe ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of pre-frontal cue-reward associations are unresolved. We trained headfixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues or licks were most common in olfactory and motor cortex, respectively. By quantifying the responses of cue-encoding neurons to six cues with varying probabilities of reward, we unexpectedly found value coding in all regions we sampled, with some enrichment in prefrontal cortex. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.
Warmer temperatures favor slower-growing bacteria in natural marine communities
Authors: Abreu Clare I. , Dal Bello Martina , Bunse Carina , Pinhassi Jarone , Gore Jeff 
Published: July 2022

AbstractEarth’s life-sustaining oceans harbor diverse bacterial communities that display varying composition across time and space. While particular patterns of variation have been linked to a range of factors, unifying rules are lacking, preventing the prediction of future changes. Here, analyzing the distribution of fast- and slow-growing bacteria in ocean datasets spanning seasons, latitude, and depth, we show that higher seawater temperatures universally favor slower-growing taxa, in agreement with theoretical predictions. Our results explain why slow growers dominate at the ocean surface, during summer, and near the tropics, and provide a framework to understand how bacterial communities will change in a warmer world.
Dietary Protection Against the Visual and Motor Deficits Induced by Experimental Autoimmune Encephalomyelitis
Authors: Zyla-Jackson Katarzyna , Walton Dorothy A. , Plafker Kendra S. , Kovats Susan , Georgescu Constantin , Brush Richard S. , Tytanic Madison , Agbaga Martin-Paul , Plafker Scott M. 
Published: July 2022

ABSTRACTFive to eight percent of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for autoimmune demyelinating diseases of the central nervous system, these treatments can be limiting for subsets of patients due to adverse effects and expense. To circumvent these barriers, we investigated a nutritional intervention in mice undergoing experimental autoimmune encephalomyelitis (EAE). This model of autoimmune-mediated demyelination induces visual and motor pathologies similar to those experienced by people with multiple sclerosis (MS). Here, we report that limiting dietary carbohydrates by feeding mice a ketogenic diet (KD) enriched in medium chain triglycerides, α-linolenic acid, and fiber is effective at mitigating EAE-induced optic neuritis and motor deficits. The KD was efficacious when fed as a preventive regimen prior to EAE immunization as well as when initiated as an interventional regimen following the onset of EAE symptoms. The KD minimally impacted body weight during the experimental time course, increased circulating ketones, prevented motor and ocular deficits, preserved myelination of the optic nerve, and reduced infiltration of immune cells to optic nerves. The KD also increased anti-inflammatory-associated omega-3 fatty acids in the plasma and reduced select cytokines in the circulation associated with EAE-mediated pathological inflammation. In light of ongoing clinical trials using dietary strategies to treat people with MS, these findings support that a KD promotes a systemic anti-inflammatory milieu and ameliorates autoimmune-induced demyelinating visual and motor deficits.
The breast cancer pro-metastatic phenotype requires concomitant hyper-activation of ECM remodeling and dsRNA-IFN1 signaling in rare clone cells
Authors: Roda Niccoló , Cossa Andrea , Hillje Roman , Tirelli Andrea , Ruscitto Federica , Cheloni Stefano , Priami Chiara , Dalmasso Alberto , Gambino Valentina , Blandano Giada , Polazzi Andrea , Falvo Paolo , Gatti Elena , Mazzarella Luca , Luzi Lucilla , Migliaccio Enrica , Pelicci Pier Giuseppe 
Published: July 2022

ABSTRACTThe molecular determinants of breast cancer (BC) pro-metastatic phenotype are largely unknown. Here, we leveraged lentiviral barcoding coupled to single-cell RNA sequencing to trace clonal and transcriptional evolution during BC metastatization. We showed that metastases derive from rare pro-metastatic clones that are under-represented in primary tumors. Both low clonal-fitness and high metastatic-potential are independent of clonal origin. Differential expression and classification analyses revealed that the pro-metastatic phenotype is acquired in rare cells by concomitant hyper-activation of extracellular-matrix remodeling, dsRNA-interferon signaling, and stress-response pathways. Notably, genetic silencing of single pro-metastatic genes from different pathways significantly impairs migration in vitro and metastatization in vivo, with negligible effects on cell proliferation and tumor growth. In addition, gene-expression signatures from identified pro-metastatic genes predicts metastatic progression in BC patients, independently of known prognostic factors. This study elucidates previously unknown mechanisms of BC metastatization, and provides novel prognosis predictors and therapeutic targets for metastasis prevention.
Simple visualization of submicroscopic protein clusters with a phase-separation-based fluorescent reporter
Authors: Mumford Thomas R. , Rae Diarmid , Brackhahn Emily , Idris Abbas , Gonzalez-Martinez David , Pal Ayush Aditya , Chung Michael C. , Guan Juan , Rhoades Elizabeth , Bugaj Lukasz J. 
Published: July 2022

ABSTRACTProtein clustering plays numerous roles in cell physiology and disease. However, protein oligomers can be difficult to detect because they are often too small to appear as puncta in conventional fluorescence microscopy. Here we describe a fluorescent reporter strategy that detects protein clusters with high sensitivity, called CluMPS (ClustersMagnified byPhaseSeparation). A CluMPS reporter detects and visually amplifies even small clusters of a binding partner, generating large, quantifiable fluorescence condensates. We use computational modeling and optogenetic clustering to demonstrate that CluMPS can detect small oligomers and behaves rationally according to key system parameters. CluMPS detected small aggregates of pathological proteins where the corresponding GFP fusions appeared diffuse. CluMPS also detected and tracked clusters of unmodified and tagged endogenous proteins, and orthogonal CluMPS probes could be multiplexed in cells. CluMPS provides a powerful yet straightforward approach to observe higher-order protein assembly in its native cellular context.
Deep-Learning for Automated Markerless Tracking of Infants General Movements
Authors: Abbasi H. , Mollet S.R , Williams S.A. , Lim L. , Battin M.R. , Besier T.F. , McMorland A.J.C. 
Published: July 2022

AbstractThe presence of abnormal infant General Movements (GMs) is a strong predictor of progressive neurodevelopmental disorders, including cerebral palsy (CP). Automation of the assessment will overcome scalability barriers that limit its delivery to at-risk individuals.Here, we report a robust markerless pose-estimation scheme, based on advanced deep-learning technology, to track infant movements in consumer mobile device video recordings. Two deep neural network models, namely Efficientnet-b6 and resnet152, were trained on manually annotated data across twelve anatomical locations (3 per limb) in 12 videos from 6 full-term infants (mean age = 17.33 (SD 2.9) wks, 4 male, 2 female), using the DeepLabCut™framework.K-fold cross-validation indicates the generalization capability of the deep-nets for GM tracking on out-of-domain data with an overall performance of 95.52% (SD 2.43) from the best performing model (Efficientnet-b6) across all infants (performance range: 84.32– 99.24% across all anatomical locations). The paper further introduces an automatic, unsupervised strategy for performance evaluation on extensive out-of-domain recordings through a fusion of likelihoods from a Kalman filter and the deep-net.Findings indicate the possibility of establishing an automated GM tracking platform, as a suitable alternative to, or support for, the current observational protocols for early diagnosis of neurodevelopmental disorders in early infancy.
BREAKING THE TIGHT GENETIC LINKAGE BETWEEN THEa1ANDsh2GENES LED TO THE DEVELOPMENT OF ANTHOCYANIN-RICH PURPLE-PERICARP SUPER-SWEETCORN
Authors: Anirban Apurba , Hayward Alice , Hong Hung T , Masouleh Ardashir Kharabian , Henry Robert J , O’Hare Tim J 
Published: July 2022

AbstractThe existence of purple-pericarp super-sweetcorn based on the most common supersweet mutation,shrunken2(sh2), has not been previously reported, partly due to its extremely tight genetic linkage to a non-functional anthocyanin biosynthesis gene,anthocyaninless1(a1). Generally, both aleurone- and pericarp-pigmented purple corn is starchy, the latter of which contains significantly higher anthocyanin compared to the former. The development of purple-pericarp super-sweetcorn is dependent on breaking thea1-sh2tight genetic linkage, which occurs at a very low frequency of <1 in 1000 meiotic crossovers. Here, to develop purple-pericarp super-sweetcorn, an initial cross between a male purple-pericarp maize (purple-round seed), ‘Costa Rica’ (A1Sh2.A1Sh2) and a female whiteshrunken2super-sweetcorn (white-shrunken seed), ‘Tims-white’ (a1sh2.a1sh2), was conducted. Subsequent self-pollination based on purple-pericarp-shrunken kernels identified a small frequency (0.08%) of initial heterozygous F3 segregants (A1a1.sh2sh2) producing a fullysh2cob with a purple-pericarp phenotype, enabled by breaking the close genetic linkage between thea1andsh2genes. Resulting rounds of self-pollination generated a F6 homozygous purple-pericarp super-sweetcorn (A1A1.sh2sh2) line, ‘Tim1’. Genome sequencing revealed a recombination break between thea1andyz1genes of thea1-yz1-x1-sh2multigenic interval, with the sequence pattern of ‘Tim1’ similar to the ‘Costa Rica’ parent, and after the linkage break, similar to the ‘Tims-white’ parent. The novel purple-pericarp super-sweetcorn produced a similar concentration of anthocyanin and sugar as in its purple-pericarp maize and white super-sweetcorn parents, respectively, potentially adding a broader range of health benefits than currently exists with standard yellow/white sweetcorn.
Robust, single-shot, optical autofocus system utilizing cylindrical lenses to provide high precision and long range of operation
Authors: Lightley J. , Kumar S. , Garcia E. , Alexandrov Y. , Dunsby C. , Neil M.A.A. , French P.M.W. 
Published: July 2022

ABSTRACTWe present a robust, “real-time” optical autofocus system for microscopy that provides high accuracy (<230 nm) and long range (∼130 µm) with a 1.4 numerical aperture oil immersion objective lens. This autofocus can operate in a closed loop, single-shot functionality over a range of ±37.5 µm and can also operate as a 2-step process up to ±68 µm. A real-time autofocus capability is useful for experiments with long image data acquisition times, including single molecule localization microscopy, that may be impacted by defocusing resulting from drift of components, e.g., due to changes in temperature or mechanical drift. It is also vital for automated slide scanning or multiwell plate imaging where the sample may not be in the same horizontal plane for every field of view during the image data acquisition. To realise high precision and long range, we implement orthogonal optical readouts using cylindrical lenses. We demonstrate the performance of this new optical autofocus system with automated multiwell plate imaging and single molecule localisation microscopy and illustrate the benefit of using a superluminescent diode as the autofocus light source.
Transcriptomic and proteomic profiling of NaV1.8-expressing mouse nociceptors
Authors: Schmidt Manuela , Sondermann Julia Regina , Gomez-Varela David , Millet Queensta , Wood John N , Zhao Jing 
Published: July 2022

ABSTRACTNociceptors play an essential role in both acute pain and chronic pain conditions. and have recently been classified into distinct subsets using single-cell transcriptional profiling. In this study, we examined protein levels in dorsal root ganglia using DIA Mass-spectrometry technologies with NaV1.8Cre+/-; ROSA26-flox-stop-flox-DTA (Diphtheria toxin fragment A) mutant mice (NaV1.8Cre-DTA), in which NaV1.8-expressing neurons (mainly nociceptors) in dorsal root ganglia (DRG) were ablated. The results show that 353 transcripts and 78 proteins, including nociceptor-specific sodium channels NaV1.8 (Scn10a) and NaV1.9 (Scn11a), were specifically expressed in nociceptors of DRG. A comparative analysis revealed that about 40% of nociceptor-specific proteins are shared within the nociceptor-specific transcript dataset. Scatter plots show that the proteome and transcriptome datasets in nociceptors have a moderate correlation (r = 0.4825), indicating the existence of post-transcriptional and post-translational gene regulation in nociceptors. This combined profiling study provides a unique resource for sensory studies, especially for pain research.
FrangiPANe, a tool for creating a panreference using left behind reads
Authors: Christine Tranchant-Dubreuil , Clothilde Chenal , Mathieu Blaison , Laurence Albar , Valentin Klein , Cédric Mariac , Wing Rod A. , Yves Vigouroux , Francois Sabot 
Published: July 2022

ABSTRACTWe present here FrangiPANe, a pipeline developed to build panreference using short reads through a map-then-assemble strategy. Applying it to 248 African rice genomes using an improved CG14 reference genome, we identified an average of 8 Mb of new sequences and 5,290 new contigs per individual. In total, 1.4 G of new sequences, consisting of 1,306,676 contigs, were assembled. We validated 97.7% of the contigs of the TOG5681 cultivar individual assembly from short reads on a newly long reads genome assembly of the same TOG5681 cultivar.FrangiPANe also allowed the anchoring of 31.5% of the new contigs within the CG14 reference genome, with a 92.5% accuracy at 2kb span. We annotated in addition 3,252 new genes absent from the reference.FrangiPANe was developed as a modular and interactive application to simplify the construction of a panreference using the map-then-assemble approach. It is available as a Docker image containing (i) a Jupyter notebook centralizing codes, documentation and interactive visualization of results, (ii) python scripts and (iii) all the software and libraries requested for each step of the analysis.We foreseen our approach will help leverage large-scale illumina dataset for pangenome studies in GWAS or detection of selection.
POLLINATOR GROOMING BEHAVIOR ALTERS POLLEN LANDSCAPES ON BEES’ BODIES AND INCREASES POLLEN CARRYOVER TO OTHER FLOWERS
Authors: Marcelo Vanessa Gonzaga , Darcie Marquitti Flávia Maria , Vallejo-Marín Mario , Brito Vinícius Lourenço Garcia de 
Published: July 2022

ABSTRACTPollen participates both as the carrier of male gametes in the reproduction of flowering plants and as a key resource exploited by floral visitors, especially bees. Pollinator behavior significantly alters the patterns of pollen removal and deposition, often called pollen fates. To date, few theoretical investigations have attempted to jointly model patterns of pollen transfer and pollinator behavior, and empirical studies are restricted to species to which pollen movement can be tracked. Here we use a spatially explicit agent-based modeling approach, to determine how bee grooming behavior may alter pollen fates and affect plant reproduction. Specifically, we asked whether pollen mixing and removal during pollen grooming may change the “pollen landscape” on a bee’s body consequently affecting both pollen export by the anthers and deposition onto stigmas. Our model shows that both mixing and removal behaviors restructure the “pollen landscape” on the bee’s body, increasing pollen carryover (deposition in consecutive visits), and increasing pollen diversity (number of pollen donors) onto stigmas in sequential flower visits. Our results counterintuitively show that pollen grooming may have a positive effect on both male and female finesses during plant reproduction.
Conditional degradation of UNC-31/CAPS enables spatiotemporal analysis of neuropeptide function
Authors: Cornell Rebecca , Cao Wei , Liu Jie , Pocock Roger 
Published: July 2022

AbstractNeuropeptide release from dense-core vesicles in Caenorhabditis elegans is promoted by UNC-31, ortholog of the calcium-dependent activator protein for secretion (CAPS). Loss of UNC-31 causes multiple phenotypes in C. elegans including reduced motility, retention of late-stage eggs and reduction in evoked synaptic release. However, the ability to analyze UNC-31 function over discrete timescales and in specific neurons is lacking. Here, we generated and validated a tool to enable UNC-31 expression and spatiotemporal functional analysis. We show that endogenously tagged UNC-31 is expressed in major ganglia and nerve cords from late-embryonic stages through to adult. Using the auxin-inducible degradation system, we depleted UNC-31 post-embryonically from the nervous system and revealed defects in egg-laying, locomotion and vesicle release that were comparable to unc-31 null mutant animals. In addition, we found that depleting UNC-31 specifically from the BAG sensory neurons causes increased intestinal fat storage, highlighting the spatial sensitivity of this system. Together, this protein degradation tool may be used to facilitate studies of neuropeptide function at precise cellular and temporal scales.Significance statementAnimal behavior and physiology is controlled by neuropeptides that are released from specific neuronal sources. The ability to dissect discrete neuropeptide functions requires precise manipulation of neuropeptide release. We have developed and validated a tool that enables precise spatiotemporal regulation of neuropeptide release that will enable researchers to examine neuropeptide function at exceptional resolution.
Adrenal sympathetic nerve mediated the anti-inflammatory effect of electroacupuncture at ST25 acupoint on a rat model of sepsis
Authors: Zhang Ziyi , Cui Xiang , Liu Kun , Gao Xinyan , Zhou QingChen , Xi Hanqing , Zhao Yingkun , Zhang Dingdan , Zhu Bing 
Published: July 2022

AbstractAcupuncture plays a vital anti-inflammatory action on sepsis through activating autonomic nerve anti-inflammatory pathways, such as sympathoadrenal medullary pathway, but the mechanism remains unclear. This study aims to explore the optimum parameter of electroacupuncture (EA) stimulation in regulating sympathoadrenal medullary pathway and evaluate EA’s anti-inflammatory effect on sepsis. To explore the optimum parameter of EA at homosegmental acupoint on adrenal sympathetic activity, the left adrenal sympathetic nerve firing rate evoked by different intensities of single shock electrical stimulation (ES) at ST25 in healthy male Sprague-Dawley (SD) rats were evaluated byin vivoelectrophysiological recording, and the levels of norepinephrine (NE) and its metabolites were also examined using mass spectrometry. To verify the role of EA at ST25 in sepsis, the rat was given intraperitoneal injection lipopolysaccharide to induce sepsis model, and survival rate, clinical score, and the level of interleukin (IL)-6, IL-1β, and IL-10 were evaluated after EA application. We observed that 3 mA is the optimal intensity on activating adrenal sympathetic nerve, which significantly elevated the level of NE in the peripheral blood. For LPS-treated rats, EA at the ST25 apparently increased the survival rate and improved the clinical score compared to the control group. Furthermore, 3 mA EA at ST25 significantly decreased pro-inflammatory cytokines IL-6 and IL-1β and upregulated anti-inflammatory cytokine IL-10 compared to the Lipopolysaccharide (LPS)-treated group. Overall, these data suggest that 3 mA is the optimal EA intensity at ST25 to activate the sympathoadrenal medullary pathway and exert an anti-inflammatory effect on sepsis.Highlights3 mA single shock ES at ST25 drove adrenal sympathetic nerve reflexs.3 mA EA at ST25 upregulated NE concentration in peripheral blood.EA at ST25 improved the survival rate in a rat of LPS-induced sepsis model.EA at the ST25 upregulated anti-inflammatory IL10 and downregulated pro-inflammatory IL1β and IL-6 in LPS-treated rats.