bluuebunny/crossref_metadata_2025_split huggingface dataset:
LSTrAP-denovo: Automated Generation of Transcriptome Atlases for Eukaryotic Species Without Genomes
Authors: Lim Peng Ken , Mutwil Marek 
Published: March 2023

Structured AbstractMotivationDespite the abundance of species with transcriptomic data, a significant number of the species still lack genomes, making it difficult to study gene function and expression in these organisms. Whilede novotranscriptome assembly can be used to assemble protein-coding transcripts from RNA-sequencing (RNA-seq) data, the datasets used often only feature samples of arbitrarily-selected or similar experimental conditions which might fail to capture condition-specific transcripts.ResultsWe developed the Large-Scale Transcriptome Assembly Pipeline forde novoassembled transcripts (LSTrAP-denovo) to automatically generate transcriptome atlases of eukaryotic species. Specifically, given an NCBI TaxID, LSTrAP-denovocan (1) filter undesirable RNA-seq accessions based on read data, (2) select RNA-seq accessions via unsupervised machine learning to construct a sample-balanced dataset for download, (3) assemble transcripts via over-assembly, (4) functionally annotate coding sequences (CDS) from assembled transcripts and (5) generate transcriptome atlases in the form of expression matrices for downstream transcriptomic analyses.Availability and ImplementationLSTrAP-denovois easy to implement, written in python, and is freely available athttps://github.com/pengkenlim/LSTrAP-denovo/.Supplementary InformationSupplementary data are available in the forms of supplementary figures, supplementary tables, and supplementary methods.
Calcium buffering tunes intrinsic excitability of spinal dorsal horn parvalbumin-expressing interneurons: A computational model
Authors: Ma Xinyue , Miraucourt Loïs , Qiu Haoyi , Sharif-Naeini Reza , Khadra Anmar 
Published: March 2023

AbstractParvalbumin-expressing interneurons (PVINs) play a crucial role within the dorsal horn of the spinal cord by preventing touch inputs from activating pain circuits. After nerve injury, their output is decreased via mechanisms that are not fully understood. In this study, we show that PVINs from nerve-injured mice change their firing pattern from tonic to adaptive. To examine the ionic mechanisms responsible for this decreased output, we employed a reparametrized Hodgkin-Huxley (HH) type model of PVINs, which predicted (1) the firing pattern transition is due to an increased contribution of small conductance calcium-activated potassium (SK) channels, enabled by (2) impairment in intracellular calcium buffering systems. Analyzing the dynamics of the HH-type model further demonstrated that a generalized Hopf bifurcation differentiates the two types of state transitions observed in the transient firing of PVINs. Importantly, this predicted mechanism holds true when we embed the PVINs model within the neuronal circuit model of the spinal dorsal horn. To experimentally validate this hypothesized mechanism, we used pharmacological modulators of SK channels and demonstrated that (1) tonic firing PVINs from naïve mice become adaptive when exposed to an SK channel activator, and (2) adapting PVINs from nerve-injured mice return to tonic firing upon SK channel blockade. Our work provides important insights into the cellular mechanism underlying the decreased output of PVINs in the spinal dorsal horn after nerve injury and highlights potential pharmacological targets for new and effective treatment approaches to neuropathic pain.Significant StatementParvalbumin-expressing interneurons (PVINs) exert crucial inhibitory control over Aβfiber- mediated nociceptive pathways at the spinal dorsal horn. The loss of their inhibitory tone leads to neuropathic symptoms, like mechanical allodynia, via mechanisms that are not fully understood. This study identifies the reduced intrinsic excitability of PVINs as a potential cause for their decreased inhibitory output in nerve-injured condition. Combining computational and experimental approaches, we predict a calcium-dependent mechanism that modulates PVINs’ electrical activity following nerve injury: a depletion of cytosolic calcium buffer allows for the rapid accumulation of intracellular calcium through the active membranes, which in turn potentiates SK channels and impedes spike generation. Our results therefore pinpoint SK channels as interesting therapeutic targets for treating neuropathic symptoms.
Drought and recovery in barley: key gene networks and retrotransposon response
Authors: Paul Maitry , Tanskanen Jaakko , Jääskeläinen Marko , Chang Wei , Dalal Ahan , Moshelion Menachem , Schulman Alan H. 
Published: March 2023

SUMMARYDuring drought, plants close their stomata at a critical soil water content (SWC), together with diverse physiological, developmental, and biochemical responses.Using precision-phenotyping lysimeters, we imposed pre-flowering drought on four barley varieties (Arvo, Golden Promise, Hankkija 673 and Morex) and followed their physiological responses. For Golden Promise, we carried out RNA-seq on leaf transcripts before and during drought, and during recovery, also examining retrotransposonBARE1expression. Transcriptional data were subjected to network analysis.The varieties differed by their critical SWC, Hankkija 673 responding at the highest and Golden Promise at the lowest. Pathways connected to drought and salinity response were strongly upregulated during drought; pathways connected to growth and development were strongly downregulated. During recovery, growth and development pathways were upregulated; altogether 117 networked genes involved in ubiquitin-mediated autophagy were downregulated. The differential response to SWC suggests adaptation to distinct rainfall patterns.We identified several strongly differentially expressed genes not earlier associated with drought response in barley.BARE1transcription is strongly transcriptionally upregulated by drought and downregulated during recovery unequally between the investigated cultivars. The downregulation of networked autophagy genes suggests a role for autophagy in drought response; its importance to resilience should be further investigated.
Cyclic di-GMP interact with putrescine via a PilZ domain receptor YcgR
Authors: Gu Weihan , Chen Yufan , Chen Zhongqiao , Gao Huagui , Xie Congcong , Zhang Lian-hui , Liao Lisheng 
Published: March 2023

AbstractThe cell motility is one of the key pathogenic factors that contribute to the virulence ofDickeya oryzea,which is a prevalent bacterial pathogen capable of infecting a range of crops and plants. We showed recently that the bacterial second messenger c-di-GMP, and the putrescine-mediated quorum sensing (QS) system, are both involved in the regulation of the bacterial motility inD. oryzeaEC1. In this study, we set to determine whether and how there two signaling mechanisms work together to modulate the bacterial motility. The results showed that the second messenger signaling system interacts with the putrescine QS system via the c-di-GMP receptor YcgR, which could promote the activity of SpeA, the rate-limiting enzyme in the putrescine biosynthesis pathway, thereby increasing the intracellular putrescine levels. However, it was shown that this facilitative effect could be inhibited by c-di-GMP molecules. In addition, we demonstrated the dominance of c-di-GMP over putrescine in the regulation of bacterial motility. The findings from this study provide the first insight into the interaction between c-di-GMP and putrescine in bacteria and provide a valuable reference for the study of intracellular second messenger system and polyamine-mediated quorum sensing system in other bacteria.ImportanceDickea oryzeais a major bacterial pathogen capable of infesting many plants and crops, causing significant economic damage to rice and banana production especially. Bacterial motility is a key pathogenic factor ofD. oryzeato compete for food resources and infect their host species, which is negatively regulated by c-di-GMP and positively regulated by putrescine, respectively. However, the connection between c-di-GMP and putrscine in regulating the motility ofD.oryzeais not understood. Here we revealed the link and the mechanism of interaction between them, showing that c-di-GMP interact with putrescine via a receptor of c-di-GMP. The significance of our research is in providing the first insight into the interaction between c-di-GMP and putrescine and the methods and experimental designs in our study will provide a valuable reference for subsequent studies on the link between c-di-GMP and putrescine in other bacteria and even the regulatory mechanisms of complex bacterial motility networks, respectively.
Social Behavior Atlas: A computational framework for tracking and mapping 3D close interactions of free-moving animals
Authors: Han Yaning , Chen Ke , Wang Yunke , Liu Wenhao , Wang Xiaojing , Liao Jiahui , Huang Yiting , Han Chuanliang , Huang Kang , Zhang Jiajia , Cai Shengyuan , Wang Zhouwei , Wu Yongji , Gao Gao , Wang Nan , Li Jinxiu , Song Yangwangzi , Li Jing , Wang Guodong , Wang Liping , Zhang Yaping , Wei Pengfei 
Published: March 2023

AbstractThe study of social behaviors in animals is essential for understanding their survival and reproductive strategies. However, accurately tracking and analyzing the social interactions of free-moving animals has remained a challenge. Existing multi-animal pose estimation techniques suffer from drawbacks such as the need for extensive manual annotation and difficulty in discriminating between similar-looking animals in close social interactions. In this paper, we present the Social Behavior Atlas (SBeA), a novel computational framework that solves these challenges by employing a deep learning-based video instance segmentation model, 3D pose reconstruction, and unsupervised dynamic behavioral clustering. SBeA framework also involves a multi-camera setup to prevent occlusion, and a novel approach to identify individual animals in close social interactions. We demonstrate the effectiveness of SBeA in tracking and mapping the 3D close interactions of free-moving animals using the example of genetic mutant mice, birds, and dogs. Our results show that SBeA is capable of identifying subtle social interaction abnormalities, and the models and frameworks developed can be applied to a wide range of animal species. SBeA is a powerful tool for researchers in the fields of neuroscience and ecology to study animal social behaviors with a high degree of accuracy and reliability.
Plasma multi-omics outlines association of urobilinogen with corticosteroid non-response, inflammation and leaky gut in Sever Alcoholic Hepatitis
Authors: Yadav Manisha , Mathew Babu , Bhat Sadam H , Sharma Neha , Kumar Jitender , Yadav Pushpa , Tripathi Gaurav , Bindal Vasundhra , Sharma Nupur , Pandey Sushmita , Singh Ravinder , Bhaskar Ashima , Dwivedi Ved Prakash , Trehanpati Nirupama , Sharma Shvetank , Sarin Shiv Kumar , Maras Jaswinder Singh 
Published: March 2023

ABSTRACTBackground and AimsSevere alcoholic hepatitis (SAH) has a high mortality and corticosteroid therapy is effective in 60% patients. Reliable indicators of response to therapy and mortality in SAH are needed. A total of 223 SAH patients, 70 in derivative [50 responders (R) and 20 non-responders (NR)] and 153 in validation cohort [136R, 17NR] were subjected to plasma metabolic/meta-proteomic analysis using UHPLC-HRMS and validated using Machine-Learning (ML). Temporal metabolic changes were assessed using Weighted Metabolome Correlation Network Analysis (WMCNA). Functionality (inflammatory-nature, effect on membrane integrity and glucocorticoid receptor) of non-response indicator was assessedin-vitroon primary healthy neutrophils or mice enterocytes. Baseline plasma metabolomics and meta-proteomics clearly discriminated NR and showed significant increase in urobilinogen (3.6-fold), cholesterol sulfate (6.9-fold), Adenosine monophosphate (4.7-fold) and others (p<0.05, FC>1.5, FDR<0.01). Increase in alpha/beta diversity, biosynthesis of secondary metabolites was a characteristic feature of NR (p<0.05). NR were metabolically inactive however R showed temporal change in the metabolite expression post-corticosteroid therapy (p<0.05). Plasma urobilinogen predicted non-response [AUC=0.94] with a hazard-ratio of 1.5(1.2-1.6) and cut-off >0.07mg/ml segregated non-survivors (p<0.01) and showed >98% accuracy using ML. Plasma urobilinogen directly correlated with circulating bacterial peptides linked to bilirubin to urobilinogen metabolising bacteria (r2>0.7;p<0.05). Urobilinogen inducedneutrophil activation,oxidative-stressandpro-inflammatory cytokines (CXCR1, NGAL, NOXO1, NOX4, IL15, TNFα and others, p<0.05), promotedcorticosteroid resistanceby increasing the expression of GR-Beta and trans-repression genes under GR-alpha (inflammatory-NFkB, MAPK-MAP) and reducing GR-alpha, and transactivation (anti-inflammatory) gene levels. Urobilinogen also promoted leaky gut by deregulating intestinal membrane junction proteins.ConclusionPlasma metabolome/meta-proteome can stratify pre-therapy steroid response. Increase in plasma Urobilinogen pedals a vicious cycle of bacterial translocation and increase in inflammation and corticosteroid non-response in SAH patients.
Crop Filling: a pipeline for repairing memory clinic MRI corrupted by partial brain coverage
Authors: Leal Gonzalo Castro , Whitfield Tim , Praharaju Janaki , Walker Zuzana , Oxtoby Neil P. 
Published: March 2023

AbstractData-driven solutions offer great promise for improving healthcare. However standard clinical neuroimaging data is subject to real-world imaging artefacts that can render the data unusable for computational research. T1 weighted structural MRI is used in research to obtain volumetric measurements from cortical and subcortical brain regions. However, clinical radiologists often prioritise T2 weighted or FLAIR scans for visual assessment. As such, T1 weighted scans are often acquired but may not be a priority. This can result in artefacts such as partial brain coverage being systematically present in memory clinic data.Here we present a neuroimaging pipeline to ameliorate such situations by filling the missing regions with synthetic data. We validate on artificially cropped scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), showing that our pipeline largely removes the artefact, improving volumetric biomarker accuracy while also retaining statistical differences between diagnostic groups. We demonstrate utility by achieving diagnostic classification performance comparable to uncorrupted data. This is an important contribution towards moving research from the lab into the real world.
The Effects of Prenatal Deaths on National Life Expectancy: Case Study U.S.A
Authors: Hollman Madeleine R. , Pearce Joshua M. 
Published: March 2023

AbstractIt is a positive indicator that human life expectancies calculated from birth have been increasing. The current standards for counting life-years, however, assume social desirability and exclude all prenatal deaths. These assumptions mask low life-year deaths and obscure results of medical and environmental interventions, thus falsely indicating higher life expectancies. This case study investigates 1930 to 2016 using CDC and World Bank data for the U.S. It is evident, published U.S. life expectancies are greatly exaggerated and what would have been short-lived Americans are disproportionately labeled as socially-undesirable and ignored when counting life years, thus presenting an overly-optimistic view of U.S. health. A comprehensive global investigation is needed, and a refinement of life expectancy calculations should be introduced, which does not bias results by only counting life expectancy from the time of live birth.
Genomic resources for a historical collection of cultivated two-row European spring barley genotypes
Authors: Schreiber Miriam , Wonneberger Ronja , Haaning Allison M. , Coulter Max , Russell Joanne , Himmelbach Axel , Fiebig Anne , Muehlbauer Gary J. , Stein Nils , Waugh Robbie 
Published: March 2023

AbstractBarley genomic resources are increasing rapidly, with the publication of a barley pangenome as one of the latest developments. Two-row spring barley cultivars are intensely studied as they are the source of high-quality grain for malting and distilling. Here we provide data from a European two-row spring barley population containing 209 different genotypes registered for the UK market between 1830 to 2014. The dataset encompasses RNA-sequencing data from six different tissues across a range of barley developmental stages, phenotypic datasets from two consecutive years of field-grown trials in the United Kingdom, Germany and the USA; and whole genome shotgun sequencing from all cultivars, which was used to complement the RNA-sequencing data for variant calling. The outcomes are a filtered SNP marker file, a phenotypic database and a large gene expression dataset providing a comprehensive resource which allows for downstream analyses like genome wide association studies or expression associations.
Immunometabolic rewiring in long COVID patients with chronic headache
Authors: Foo Suan-Sin , Chen Weiqiang , Jung Kyle L. , Azamor Tamiris , Choi Un Yung , Zhang Pengfei , Comhair Suzy AA , Erzurum Serpil C. , Jehi Lara , Jung Jae U. 
Published: March 2023

AbstractAlmost 20% of patients with COVID-19 experience long-term effects, known as post-COVID condition or long COVID. Among many lingering neurologic symptoms, chronic headache is the most common. Despite this health concern, the etiology of long COVID headache is still not well characterized. Here, we present a longitudinal multi-omics analysis of blood leukocyte transcriptomics, plasma proteomics and metabolomics of long COVID patients with chronic headache. Long COVID patients experienced a state of hyper-inflammation prior to chronic headache onset and maintained persistent inflammatory activation throughout the progression of chronic headache. Metabolomic analysis also revealed augmented arginine and lipid metabolisms, skewing towards a nitric oxide-based pro-inflammation. Furthermore, metabolisms of neurotransmitters including serotonin, dopamine, glutamate, and GABA were markedly dysregulated during the progression of long COVID headache. Overall, these findings illustrate the immuno-metabolomics landscape of long COVID patients with chronic headache, which may provide insights to potential therapeutic interventions.
Hyperglycemic exacerbation of myocardial infarction through SGLT1 - a glucose paradox
Authors: Almalki Alhanoof , Arjun Sapna , Harding Idris , Jasem Hussain , Kolatsi-Joannou Maria , Jafree Daniyal J , Long David A , Yellon Derek M , Bell Robert M 
Published: March 2023

AbstractBackgroundHyperglycemia is common during acute myocardial infarction, irrespective of diabetic status, and portends excess mortality. The mechanisms of this adverse outcome remain unelucidated.ObjectivesTo test the hypothesis that elevated glucose, at the time of reperfusion following myocardial ischemia, is directly injurious to the heart through induction of sodium/glucose-linked transporter 1 (SGLT1) activity.MethodsEx-vivo, Langendorff rodent models of 35minute global ischemia and 2hour reperfusion injury were utilised, with variable glucose and reciprocal mannitol concentrations maintaining equivalent osmolarity across groups during reperfusion. Infarct size was assessed by tri-phenyltetrazolium staining. SGLT1 expression was determined in rodents by rtPCR, RNAscope and immunohistochemistry and in human with single-cell transcriptomic analysis.Ex-vivo, functional involvement of SGLT1 was determined using three, structurally distinct pharmacological inhibitors: phlorizin, canagliflozin and mizagliflozin.ResultsIn non-diabetic rodent hearts there was a J-shaped dose-response relationship between reperfusion-glucose concentration and infarct size, an association ameliorated in diabetic heart. Single-cell transcriptomic analysis revealed human myocardial SGLT1 expression equivalent to that seen in rodents at both an RNA and protein level. Diabetic rodent heart SGLT1 expression was significantly reduced compared to non-diabetic, and pharmacological SGLT1 inhibition abrogated excess injury associated with high glucose in non-diabetic heart.ConclusionElevated glucose during reperfusion exacerbated myocardial infarction in non-diabetic heart, but this exacerbation was attenuated in diabetic rat heart where SGLT1 expression is suppressed. Inhibiting non-diabetic heart SGLT1 abrogates the excess injury associated with elevated glucose, thus highlighting SGLT1 as a potential clinical translational target to improve outcomes in acute myocardial infarction associated with hyperglycemia.
“How Social Connection and Engagement Relate to Functional Limitations and Depressive Symptoms Outcomes After Stroke”
Authors: Elayoubi Joanne , Haley William E. , Nelson Monica E. , Hueluer Gizem 
Published: March 2023

AbstractBackgroundStroke commonly leads to disability and depression. Social connection and engagement can be protective against functional decline and depression in the general population. We investigated the effects of social connection and engagement on trajectories of function and depressive symptoms in stroke.MethodsParticipants were 898 individuals with incident stroke from the Health and Retirement Study between 1998-2012. Multilevel modeling was used to examine associations of social connection and engagement with changes in functional limitations in instrumental activities of daily living (IADLs) and depressive symptoms over time. Models controlled for age, gender, education, and race/ethnicity. Moderation analyses examined whether high social connection and engagement reduced depressive symptoms for survivors with high IADL impairment.ResultsSocial connection and engagement were generally associated with fewer IADL limitations and depressive symptoms at the time of stroke and after stroke. For example, participants who felt lonely and did not provide help to others before stroke had more IADL limitations. Pre-stroke volunteering was associated with less increase in IADL limitations with stroke and increase in having friends and providing help to others compared to one’s pre-stroke status were associated with fewer IADL limitations after stroke. For depressive symptoms, participants who felt lonely and did not have a friend or partner before stroke had more depressive symptoms, and participants who had children residing nearby before stroke showed less increase in depressive symptoms. Moderation effects were not found for social connection and engagement on high IADL impairment and depressive symptoms.ConclusionsFindings suggest that social connection and engagement may reduce the negative physical and psychological outcomes of stroke, both at baseline and after stroke. Efforts to enhance social engagement and diminish loneliness may both enhance population well-being and enhance resilience and recovery from stroke and other illnesses.