bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatosensory Cortical Signature of Facial Nociception and Vibrotactile Touch Induced Analgesia
Authors: Lu Jinghao , Chen Bin , Levy Manuel , Xu Peng , Han Bao-Xia , Takatoh Jun , Thompson P. M. , He Zhigang , Prevosto Vincent , Wang Fan 
Published: April 2022

AbstractPain relief by vibrotactile touch is a common human experience. Previous neurophysiological investigations in animals focused on spinal mechanisms while human studies suggested the involvement of supraspinal mechanisms. Here we asked whether and how the primary somatosensory cortex (S1) is involved in touch induced analgesia. We discovered that in mice, vibrotactile reafferent signals from self-generated whisking significantly reduce facial nociception, which is abolished by specifically blocking touch transmission from thalamus to the barrel cortex (S1B). The presence of whisking altered nociceptive signal processing in S1B neurons. Intrinsic manifold analysis of S1B population activity revealed that whisking pushes the transition of neural state induced by noxious stimuli towards the state encoding non-nocifensive actions. Thus, S1B integrates facial tactile and noxious signals to enable touch mediated analgesia.TeaserVibrotactile signals modulate barrel cortex population dynamics during touch mediated facial analgesia
PvC3H29 interacts with and inhibits DNA binding of PvNAPs to finetune leaf senescence in switchgrass (Panicum virgatum)
Authors: Xie Zheni , Yu Guohui , Lei Shanshan , Wang Hui , Xu Bin 
Published: April 2022

AbstractFinetuning the progression of leaf senescence is important for plant’s fitness in nature, while ‘staygreen’ with delayed leaf senescence has been considered as a valuable agronomic trait in crop genetic improvement. In this study, a switchgrass CCCH-type Zinc finger gene, PvC3H29, was characterized as a suppressor of leaf senescence that over-expressing or suppressing the gene led to delayed or accelerated leaf senescence, respectively. Transcriptomic analysis marked that chlorophyll catabolic pathway genes were involved in the PvC3H29-regulated leaf senescence. PvC3H29 was a nucleus-localized protein with no transcriptional activity. By Y2H screening, we identified its interacting proteins, including a pair of paralogous transcription factors, PvNAP1&2. Over-expressing the PvNAPs led to precocious leaf senescence at least partially by directly targeting and transactivating chlorophyll catabolic genes to promote chlorophyll degradation. PvC3H29, through protein-protein interaction, repressed the DNA-binding efficiency of PvNAPs and alleviated its transactivating effect on downstream genes, thereby functioned as a ‘brake’ in the progression of leaf senescence. Moreover, over-expressing PvC3H29 resulted in up to 47% higher biomass yield and improved biomass feedstock quality, reiterating the importance of leaf senescence regulation in the genetic improvement of switchgrass and other feedstock crops.One-sentence summaryPvC3H29 interacts with transcription factors, PvNAP1&2, to inhibit their transactivation on chlorophyll catabolism and leaf senescence in switchgrass.
Supervised spatial inference of dissociated single-cell data with SageNet
Authors: Heidari Elyas , Lohoff Tim , Tyser Richard C. V. , Marioni John C. , Robinson Mark D. , Ghazanfar Shila 
Published: April 2022

ABSTRACTSpatially-resolved transcriptomics uncovers patterns of gene expression at supercellular, cellular, or subcellular resolution, providing insights into spatially variable cellular functions, diffusible morphogens, and cell-cell interactions. However, for practical reasons, multiplexed single cell RNA-sequencing remains the most widely used technology for profiling transcriptomes of single cells, especially in the context of large-scale anatomical atlassing. Devising techniques to accurately predict the latent physical positions as well as the latent cell-cell proximities of such dissociated cells, represents an exciting and new challenge. Most of the current approaches rely on an ‘autocorrelation’ assumption, i.e., cells with similar transcriptomic profiles are located close to each other in physical space and vice versa. However, this is not always the case in native biological contexts due to complex morphological and functional patterning. To address this challenge, we developed SageNet, a graph neural network approach that spatially reconstructs dissociated single cell data using one or more spatial references. SageNet first estimates a gene-gene interaction network from a reference spatial dataset. This informs the structure of the graph on which the graph neural network is trained to predict the region of dissociated cells. Finally, SageNet produces a low-dimensional embedding of the query dataset, corresponding to the reconstructed spatial coordinates of the dissociated tissue. Furthermore, SageNet reveals spatially informative genes by extracting the most important features from the neural network model. We demonstrate the utility and robust performance of SageNet using molecule-resolved seqFISH and spot-based Spatial Transcriptomics reference datasets as well as dissociated single-cell data, across multiple biological contexts. SageNet is provided as an open-source python software package at https://github.com/MarioniLab/SageNet.
Rare Monoclonal Antibody Discovery Based on Indirect Competitive Screening of Single Hapten-specific Rabbit Antibody Secreting Cell
Authors: Li Yuan , Li Peipei , Ke Yuebin , Yu Xuezhi , Yu Wenbo , Wen Kai , Shen Jianzhong , Wang Zhanhui 
Published: April 2022

ABSTRACTRare antibody that is able to tolerate physio-chemical factors is preferred and highly demanded in diagnosis and therapy. Rabbit monoclonal antibodies (RmAbs) are distinguished owing to their high affinity and stability. However, the efficiency and availability of traditional methods for RmAb discovery are limited, especially for small molecules. Here, we present an indirect competitive screening method in nanowells, named CSMN, for single rabbit antibody secreting cells (ASCs) selection with 20.6 h and proposed an efficient platform for RmAb production against small molecule with 5.8 days for the first time. Chloramphenicol (CAP) as an antibacterial agent has the great threats for public health. We applied the CSMN to select CAP-specific ASCs and produced one high affinity RmAb, surprisingly showing extremely halophilic properties with an IC50of 0.08 ng mL-1in saturated salt solution which has as yet not been shown by other antibodies. Molecular dynamic simulation showed that the negatively charged surface improved the stability of the RmAb structure with additional disulfide bonds compared with mouse antibody. Moreover, the reduced solvent accessible surface area of the binding pocket increased the interactions of RmAb with CAP in a saturated salt solution. Furthermore, the RmAb was used to develop an immunoassay for the detection of CAP in real biological samples with simple pretreatment, shorter assay time, and higher sensitivity. The results demonstrated that the practical and efficient CSMN is suitable for rare RmAb discovery against small molecules.
Biological misinterpretation of transcriptional signatures in tumour samples can unknowingly undermine mechanistic understanding and faithful alignment with preclinical data
Authors: Fisher Natalie C , Byrne Ryan M , Leslie Holly , Wood Colin , Legrini Assya , Cameron Andrew J , Ahmaderaghi Baharak , Corry Shania , Malla Sudhir , Amirkhah Raheleh , McCooey Aoife , Rogan Emily , Redmond Keara L , Sakhnevych Svetlana , Domingo Enric , Jackson James , Loughrey Maurice B , Leedham Simon , Maughan Tim , Lawler Mark , Sansom Owen J , Lamrock Felicity , Koelzer Viktor H , Jamieson Nigel , Dunne Philip D 
Published: April 2022

AbstractPrecise mechanism-based gene expression signatures (GESs) have been developed in appropriate in vitro and in vivo model systems, to identify important cancer-related signalling processes. However, some GESs originally developed to represent specific disease processes, primarily with an epithelial cell focus, are being applied to heterogeneous tumour samples where the expression of the genes in the signature may no longer be epithelial-specific. Therefore, unknowingly, even small changes in tumour stroma percentage can directly influence GESs, undermining the intended mechanistic signalling.Using colorectal cancer as an exemplar, we deployed numerous orthogonal profiling methodologies, including laser capture microdissection, flow cytometry, bulk and multiregional biopsy clinical samples, single cell RNAseq and finally spatial transcriptomics, to perform a comprehensive assessment of the potential for the most widely-used GESs to be influenced, or confounded, by stromal content in tumour tissue. To complement this work, we generated a freely-available resource, ConfoundR; https://confoundr.qub.ac.uk/, that enables users to test the extent of stromal influence on an unlimited number of the genes/signatures simultaneously across colorectal, breast, pancreatic, ovarian and prostate cancer datasets.Findings presented here demonstrate the clear potential for misinterpretation of the meaning of GESs, due to widespread stromal influences, which in-turn can undermine faithful alignment between clinical samples and preclinical data/models, particularly cell lines and organoids, or tumour models not fully recapitulating the stromal and immune microenvironment. As such, efforts to faithfully align preclinical models of disease using phenotypically-designed GESs must ensure that the signatures themselves remain representative of the same biology when applied to clinical samples.
3DPolyS-LE: an accessible simulation framework to model the interplay between chromatin and loop extrusion
Authors: Gitchev Todor , Zala Gabriel , Meister Peter , Jost Daniel 
Published: April 2022

AbstractMotivationRecent studies suggest that the loop extrusion activity of Structural Maintenance of Chromosomes complexes is central to proper organization of genomes in vivo. Polymer physics-based modeling of chromosome structure has been instrumental to assess which structures such extrusion can create. Only few laboratories however have the technical and computational expertise to create in silico models combining dynamic features of chromatin and loop extruders.ResultsHere we present 3DPolyS-LE, a self-contained, easy to use modeling and simulation framework allowing non-specialists to ask how specific properties of loop extruders and boundary elements impact on 3D chromosome structure. 3DPolyS-LE also provides algorithms to compare predictions with experimental Hi-C data.Availability and implementationSoftware available at https://gitlab.com/togop/3DPolyS-LE ; implemented in Python and Fortran 2003 and supported on any Unix-based operating system (Linux, Mac OS).Contactpeter.meister@unibe.ch and daniel.jost@ens-lyon.frSupplementary InformationSupplemental data are available at Bioinformatics online
Meta-analysis using new methods for three-stressor combinations reveal substantial higher-order interactions and emergent properties
Authors: Diamant Eleanor S. , Boyd Sada , Lozano-Huntelman Natalie Ann , Enriquez Vivien , Kim Alexis R. , Savage Van M. , Yeh Pamela J. 
Published: April 2022

AbstractAlthough natural populations are typically subjected to multiple stressors, most past research has focused on single stressors and two-stressor interactions, with little attention paid to higher-order interactions among three or more stressors. However, higher-order interactions increasingly appear to be widespread. Consequently, we used a recently introduced and improved framework to re-analyze higher-order ecological interactions. We conducted a literature review of the last 100 years (1920-2020) and reanalyzed 151 ecological three-stressor interactions from 45 published papers. We found that 89% (n=134) of the three-stressor combinations resulted in new or different interactions than previously reported. We also found substantial levels of emergent properties— interactions that are only revealed when all three stressors are present. Antagonism was the most prevalent net interaction whereas synergy was the most prevalent emergent interaction. Understanding multiple stressor interactions is crucial for fundamental questions in ecology and also has implications for conservation biology and population management.
mGlu2and mGlu3receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats
Authors: Tyler Ryan E. , Van Voorhies Kalynn , Blough Bruce E. , Landavazo Antonio , Besheer Joyce 
Published: April 2022

AbstractRationaleThe subjective effects of alcohol are associated with alcohol use disorder (AUD) vulnerability and treatment outcomes. The interoceptive effects of alcohol are part of these subjective effects and can be measured in animal models using drug discrimination procedures. The newly developed mGlu2and mGlu3negative allosteric modulators (NAMs) are potential therapeutics for AUD and may alter interoceptive sensitivity to alcohol.ObjectivesTo determine the effects of mGlu2and mGlu3NAMs on the interoceptive effects of alcohol in rats.MethodsLong-Evans rats were trained to discriminate the interoceptive stimulus effects of alcohol (2.0 g/kg, i.g.) from water using both operant (males only) and Pavlovian (male and female) drug discrimination techniques. Following acquisition training, an alcohol dose-response (0, 0.5, 1.0, 2.0 g/kg) experiment was conducted to confirm stimulus control over behavior. Next, to test the involvement of mGlu2and mGlu3, rats were pretreated with the mGlu2-NAM (VU6001966; 0, 3, 6, 12 mg/kg, i.p.) or the mGlu3-NAM (VU6010572; 0, 3, 6, 12 mg/kg, i.p.) before alcohol administration (2.0 g/kg, i.g.).ResultsIn Pavlovian discrimination, male rats showed greater interoceptive sensitivity to 1.0 and 2.0 g/kg alcohol compared to female rats. Both mGlu2-NAM and mGlu3-NAM attenuated the interoceptive effects of alcohol in male and female rats using Pavlovian and operant discrimination. There may be a potential sex difference in response to the mGlu2-NAM at the highest dose tested.ConclusionsMale rats may be more sensitive to the interoceptive effects of 2.0 g/kg alcohol training dose compared to female rats. Both mGlu2and mGlu3NAM attenuate the interoceptive effects of alcohol in male and female rats. Sex differences in mGlu2-NAM sensitivity were observed. These drugs may have potential for treatment of AUD in part by blunting the subjective effects of alcohol.
Inferring functions of coding and non-coding genes using epigenomic patterns and deciphering the effect of combinatorics of transcription factors binding at promoters
Authors: Chandra Omkar , Sharma Madhu , Pandey Neetesh , Jha Indra Prakash , Mishra Shreya , Kong Say Li , Kumar Vibhor 
Published: April 2022

AbstractThe number of annotated genes in the human genome has increased tremendously, and understanding their biological role is challenging through experimental methods alone. There is a need for a computational approach to infer the function of genes, particularly for non-coding RNAs, with reliable explainability. We have utilized genomic features that are present across both coding and non-coding genes like transcription factor (TF) binding pattern, histone modifications, and DNase hypersensitivity profiles to predict ontology-based functions of genes. Our approach for gene function prediction (GFPred) made reliable predictions (>90% balanced accuracy) for 486 gene-sets. Further analysis revealed that predictability using only TF-binding patterns at promoters is also high, and it paved the way for studying the effect of their combinatorics. The predicted associations between functions and genes were validated for their reliability using PubMed abstract mining. Clustering functions based on shared top predictive TFs revealed many latent groups of gene-sets involved in common major biological processes. Available CRISPR screens also supported the inferred association of genes with the major biological processes of latent groups of gene-sets. For the explainability of our approach, we also made more insights into the effect of combinatorics of TF binding (especially TF-pairs) on association with biological functions.
A cobB like protein in Oryza sativa indica regulates the mitochondrial machinery under stress conditions
Authors: Khan Sonali , Mitra Nilabhra , Dey Sanghamitra 
Published: April 2022

ABSTRACTSirtuins are ubiquitous in nature and are known to play an important role as metabolic regulators. In plants, these NAD+ dependent deacetylases are not well characterized. In this study, we are reporting a new member of sirtuin in Oryza sativa indica. It shares approx. 89% sequence identity with bacterial sirtuin, a class III sirtuin member. This protein is mostly present in mitochondria with trace amounts in the nucleus. It can physically interact with histones H3 and H4 and can specifically deacetylate histone H3 at K9 and K18 positions. In mitochondria, acetyl coA synthetase (AcS) and isocitrate dehydrogenase (IDH2) are the targets for its deacetylation. This removal of acetyl group is the mode of regulation under certain stress conditions. Thus, this is the first mitochondrial cobB targeting important plant machinery under changing growth environment. The OscobB deacetylase activity is not majorly affected by its products, NAM & ADP ribose but are sensitive to certain metal ions like Fe2+ and Mg2+. In contrast to some class III members, it does not have any ADP ribosyl transferase activity. In response to abiotic stress conditions like dehydration and low temperature, this enzyme can also mobilize to the nucleus to regulate the plant metabolism.HighlightsA new class III member of the sirtuin family found in Oryza sativa indica.Under normal conditions, this protein is localized mostly in mitochondria, with trace amounts in the nucleus.This enzyme is capable of using both NAD+ and NADP+ as a substrate for catalysis.It specifically deacetylates the nuclear histone H3 at K9 and K18 positions.Mitochondrial proteins acetyl coA synthetase (AcS) and isocitrate dehydrogenase (IDH2) are the regulatory targets of OscobB.Under certain stress conditions in plants like dehydration, pathogenesis and low temperature, there is localisation of OscobB from mitochondria to nucleus.
Newly discovered alleles of the tomato antiflorigen gene SELF PRUNING provide a range of plant compactness and yield
Authors: Kang Min-Sung , Kim Yong Jun , Heo Jung , Rajendran Sujeevan , Wang Xingang , Bae Jong Hyang , Lippman Zachary , Park Soon Ju 
Published: April 2022

AbstractIn tomato cultivation, a rare natural mutation in the flowering repressor antiflorigen gene SELF-PRUNING (sp-classic) induces precocious shoot termination and is the foundation in determinate tomato breeding for open field production. Heterozygosity for induced mutations in the florigen gene SINGLE FLOWER TRUSS in the background of sp-classic provides a heterosis-like effect by delaying shoot termination, suggesting subtle suppression of determinacy by genetic modification of florigen-antiflorigen balance could improve yield. Here, we isolated three new sp alleles from the tomato germplasm that show modified determinate growth compared to sp-classic, including one allele that mimics the effect of sft heterozygosity. Two deletion alleles eliminate functional transcripts and showed similar shoot termination, determinate growth, and yields as sp-classic. In contrast, amino acid substitution allele sp-5732 showed semi-determinate growth with more leaves and sympodial shoots on all shoots. This translated to greater yield compared to the other stronger alleles by up to 42%. Transcriptome profiling of axillary (sympodial) shoot meristems (SYM) from sp-classic and wild type plants revealed six mis-regulated genes related to the floral transition, which were used as biomarkers to show that the maturation of SYMs in the weaker sp-5732 genotype is delayed compared to sp-classic, consistent with delayed shoot termination and semi-determinate growth. Assessing sp allele frequencies from over 500 accessions indicated that one of the strong sp alleles (sp-2798) arose in early breeding cultivars but was not selected. The newly discovered sp alleles are potentially valuable resources to quantitatively manipulate shoot growth and yield in determinate breeding programs, with sp-5732 providing an opportunity to develop semi-determinate field varieties with higher yields.
HOPX governs a molecular and physiological switch between cardiomyocyte progenitor and maturation gene programs
Authors: Friedman Clayton E. , Cheetham Seth W. , Mills Richard J. , Ogawa Masahito , Redd Meredith A. , Chiu Han Sheng , Shen Sophie , Sun Yuliangzi , Mizikovsky Dalia , Bouveret Romaric , Chen Xiaoli , Voges Holly , Paterson Scott , De Angelis Jessica E. , Andersen Stacey B. , Yoon Sohye , Faulkner Geoffrey J. , Smith Kelly A. , Harvey Richard P. , Hogan Benjamin M. , Nguyen Quan , Kikuchi Kazu , Hudson James E. , Palpant Nathan J. 
Published: April 2022

SUMMARYThis study establishes the homeodomain only protein, HOPX, as a determinant controlling the molecular switch between cardiomyocyte progenitor and maturation gene programs. Time-course single-cell gene expression with genome-wide footprinting reveal that HOPX interacts with and controls core cardiac networks by regulating the activity of mutually exclusive developmental gene programs. Upstream hypertrophy and proliferation pathways compete to regulate HOPX transcription. Mitogenic signals override hypertrophic growth signals to suppress HOPX and maintain cardiomyocyte progenitor gene programs. Physiological studies show HOPX directly governs genetic control of cardiomyocyte cell stress responses, electro-mechanical coupling, proliferation, and contractility. We use human genome-wide association studies (GWAS) to show that genetic variation in the HOPX-regulome is significantly associated with complex traits affecting cardiac structure and function. Collectively, this study provides a mechanistic link situating HOPX between competing upstream pathways where HOPX acts as a molecular switch controlling gene regulatory programs underpinning metabolic, signaling, and functional maturation of cardiomyocytes.
Using the consumption values to investigate consumer purchase intentions towards natural food products
Authors: Chakraborty Debarun , Dash Ganesh 
Published: April 2022

PurposeNatural food products are becoming more popular, and their health-related benefits are widely acknowledged. The authors wanted to see the influence of different consumption values on purchase intention of natural food products. To address this gap, the current study proposes to use theory of consumption values to explain customers purchase intention towards natural food products.Design/methodology/approachThe authors used theory of consumption values (TCV), attitude and purchase intention to develop a comprehensive model. About 464 respondents have responded to the structured questionnaire which was floated through email and WhatsApp. Finally, the authors used structural equation modelling and moderation analysis to arrive at the final results.FindingsExcept for social value, all constructs named conditional, functional, emotional and epistemic were found to have a favourable and significant impact on consumers’ purchase intention towards natural food products. The study shows that attitude has a moderating effect on the association between emotional value and purchase intention.Research limitations/implicationsThis research illuminates the TCV which enable the long-term use of natural food products. In addition, the importance of attitude as a moderator of purchase intent provides a deep understanding of customer behaviour.Originality/valueThis model is the first of its kind in the current literature, using consumption values from the TCV with attitude to regulate purchase intention towards natural food products. In addition, theoretical advancements pave the path for future research.