bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Culture Alters Cell Lineage Composition and Cellular Metabolism of Bovine Blastocyst
Authors: Ming Hao , Zhang Mingxiang , Rajput Sandeep , Logsdon Deirdre , Zhu Linkai , Schoolcraft William B , Krisher Rebecca , Jiang Zongliang , Yuan Ye 
Published: June 2023

AbstractProfiling transcriptome at single cell level of bovine blastocysts derived in vivo (IVV), in vitro from conventional culture medium (IVC), and reduced nutrient culture medium (IVR) has enabled us to reveal cell lineage segregation, during which forming inner cell mass (ICM), trophectoderm (TE), and an undefined population of transitional cells. Only IVV embryos had well-defined ICM, indicating in vitro culture may delay the first cell fate commitment to ICM. Differences between IVV, IVC and IVR embryos were mainly contributed by ICM and transitional cells. Pathway analysis by using the differentially expressed genes of these non-TE cells between groups pointed to highly active metabolic and biosynthetic processes, with reduced cellular signaling and membrane transport in IVC embryos, which may lead to reduced developmental potential. IVR embryos had lower activities in metabolic and biosynthetic processes, but increased cellular signaling and membrane transport, suggesting these cellular mechanisms may contribute to the improved blastocyst development compared to IVC embryos. However, the IVR embryos had compromised development when compared to IVV embryos with notably over-active membrane transport activities that led to impaired ion homeostasis.Summary StatementSingle-cell transcriptomic analysis of bovine blastocysts produced in vivo, and in vitro in conventional and reduced nutrient conditions reveals the effect of culture environments on embryo developmental potential.
Single-cell RNA sequencing identifies response of renal lymphatic endothelial cells to acute kidney injury
Authors: Creed Heidi A. , Kannan Saranya , Tate Brittany L. , Banerjee Priyanka , Mitchell Brett M. , Chakraborty Sanjukta , Rutkowski Joseph M. 
Published: June 2023

ABSTRACTThe inflammatory response to acute kidney injury (AKI) likely dictates future renal health. Lymphatic vessels are responsible for maintaining tissue homeostasis through transport and immunomodulatory roles. Due to the relative sparsity of lymphatic endothelial cells (LECs) in the kidney, past sequencing efforts have not characterized these cells and their response to AKI. Here we characterized murine renal LEC subpopulations by single-cell RNA sequencing and investigated their changes in cisplatin AKI. We validated our findings by qPCR in LECs isolated from both cisplatin-injured and ischemia reperfusion injury, by immunofluorescence, and confirmation inin vitrohuman LECs. We have identified renal LECs and their lymphatic vascular roles that have yet to be characterized in previous studies. We report unique gene changes mapped across control and cisplatin injured conditions. Following AKI, renal LECs alter genes involved endothelial cell apoptosis and vasculogenic processes as well as immunoregulatory signaling and metabolism. Differences between injury models are also identified with renal LECs further demonstrating changed gene expression between cisplatin and ischemia reperfusion injury models, indicating the renal LEC response is both specific to where they lie in the lymphatic vasculature and the renal injury type. How LECs respond to AKI may therefore be key in regulating future kidney disease progression.
Detecting haplotype-specific transcript variation in long reads with FLAIR2
Authors: Tang Alison D. , Hrabeta-Robinson Eva , Volden Roger , Vollmers Christopher , Brooks Angela N. 
Published: June 2023

AbstractBackgroundRNA-Seq has brought forth significant discoveries regarding aberrations in RNA processing, implicating these RNA variants in a variety of diseases. Aberrant splicing and single nucleotide variants in RNA have been demonstrated to alter transcript stability, localization, and function. In particular, the upregulation of ADAR, an enzyme which mediates adenosine-to-inosine editing, has been previously linked to an increase in the invasiveness of lung ADC cells and associated with splicing regulation. Despite the functional importance of studying splicing and SNVs, short read RNA-Seq has limited the community’s ability to interrogate both forms of RNA variation simultaneously.ResultsWe employed long-read technology to obtain full-length transcript sequences, elucidating cis-effects of variants on splicing changes at a single molecule level. We have developed a computational workflow that augments FLAIR, a tool that calls isoform models expressed in long-read data, to integrate RNA variant calls with the associated isoforms that bear them. We generated nanopore data with high sequence accuracy of H1975 lung adenocarcinoma cells with and without knockdown ofADAR. We applied our workflow to identify key inosine-isoform associations to help clarify the prominence of ADAR in tumorigenesis.ConclusionsUltimately, we find that a long-read approach provides valuable insight toward characterizing the relationship between RNA variants and splicing patterns.HighlightsFLAIR2 has improved transcript isoform detection and incorporates sequence variants for haplotype-specific transcript detection.In addition to haplotype-specific variant detection, it identifies transcript-specific RNA editingAble to identify haplotype-specific transcript isoform bias in expressionLong-read sequencing identifies hyperedited transcripts that are missed from short-read sequencing methods for a more comprehensive identification of ADAR targets
13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8+T cells
Authors: Ma Eric H. , Dahabieh Michael S. , DeCamp Lisa M. , Kaymak Irem , Kitchen-Goosen Susan M. , Roy Dominic G. , Verway Mark J. , Johnson Radia M. , Samborska Bozena , Scullion Catherine A. , Steadman Mya , Vos Matthew , Roddy Thomas P. , Krawczyk Connie M. , Williams Kelsey S. , Sheldon Ryan D. , Jones Russell G. 
Published: June 2023

AbstractInfusion of 13C-labeled metabolites provides a gold-standard for understanding the metabolic processes used by T cells during immune responsesin vivo. Through infusion of 13C-labeled metabolites (glucose, glutamine, acetate) inListeria monocytogenes(Lm)-infected mice, we demonstrate that CD8+ T effector (Teff) cells utilize metabolites for specific pathways during specific phases of activation. Highly proliferative early Teff cellsin vivoshunt glucose primarily towards nucleotide synthesis and leverage glutamine anaplerosis in the tricarboxylic acid (TCA) cycle to support ATP andde novopyrimidine synthesis. Additionally, early Teff cells rely on glutamic-oxaloacetic transaminase 1 (Got1)—which regulatesde novoaspartate synthesis—for effector cell expansionin vivo. Importantly, Teff cells change fuel preference over the course of infection, switching from glutamine-to acetate-dependent TCA cycle metabolism late in infection. This study provides insights into the dynamics of Teff metabolism, illuminating distinct pathways of fuel consumption associated with Teff cell functionin vivo.TeaserInterrogating dynamics of fuel utilization by CD8+T cellsin vivoreveals new metabolic checkpoints for immune functionin vivo.
Soil chemical and microbial gradients determine accumulation of root exuded secondary metabolites and plant-soil feedbacks in the field
Authors: Gfeller Valentin , Cadot Selma , Waelchli Jan , Gulliver Sophie , Terrettaz Céline , Thönen Lisa , Mateo Pierre , Robert Christelle A.M. , Mascher Fabio , Steinger Thomas , Bigalke Moritz , Erb Matthias , Schlaeppi Klaus 
Published: June 2023

AbstractIntroductionHarnessing positive plant-soil feedbacks via crop rotations is a promising strategy for sustainable agriculture. Plants can influence soil properties including microbes by exuding specialized metabolites. However, the effects are often context dependent and variable. If and how local soil heterogeneity may explain this variation is unknown. Benzoxazinoids are specialized metabolites that are released in high quantities by cereals such as wheat and maize. Benzoxazinoids can alter rhizosphere microbiota and the performance of plants subsequently growing in the exposed soils and are thus an excellent model to study agriculturally relevant plant-soil feedbacks in the field, and to assess how soil factors affect their outcome.Materials & methodsTo understand the importance of local variation in soil properties on benzoxazinoid-mediated plant-soil feedbacks, we conditioned plots with wild-type maize and benzoxazinoid-deficientbx1mutant plants in a grid pattern across an arable field. We then grew winter wheat across the entire field in the following season. We determined accumulation of benzoxazinoids, root-associated microbial communities, abiotic soil properties and wheat performance in each plot. We also determined benzoxazinoid conversion dynamics in a labelling experiment under controlled conditions, and then assessed associations between soil chemical variation and benzoxazinoid-mediated plant-soil feedbacks.ResultsAcross the field, we detected a marked gradient in soil chemical and microbial community composition. This gradient resulted in significant differences in benzoxazinoid accumulation. These differences were explained by differential benzoxazinoid degradation rather than exudation. Benzoxazinoid exudation modulated alpha diversity of root and rhizosphere bacteria and fungi during maize growth, but not during subsequent wheat growth, while the chemical fingerprint of benzoxazinoid accumulation persisted. Averaged across the field, we detected no significant feedback effects of benzoxazinoid conditioning on wheat performance and defence, apart from a transient decrease in biomass during vegetative growth. Closer analysis however, revealed pronounced feedback effects along the chemical and microbial gradient of the field, with effects gradually changing from negative to positive along the gradient.ConclusionOverall, this study revealed that plant-soil feedbacks differ in strength and direction within a field, and that this variation can be explained by standing chemical and microbial gradients, which strongly affect benzoxazinoid accumulation in the soil. Understanding within-field soil heterogeneity is crucial for the future exploitation of plant-soil feedbacks in sustainable precision agriculture.
Increased cardiovascular mortality in patients with mechanically expandable transcatheter aortic valve and without permanent pacemaker
Authors: Hájek Petr , Adlová Radka , Horváth Martin , Hansvenclová Eva , Pecková Monika , Veselka Josef 
Published: June 2023

AbstractIntroductionUse of the mechanically expandable transcatheter aortic valve (MEV) has been recently linked to increased risks of valve dysfunction and cardiovascular mortality. The risk of developing conduction disturbance with the MEV valve is well-known, and the negative prognostic impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is another consideration.AimThis study aimed to compare the mid-term survival of patients with MEV and self-expandable valves (SEV), and to examine survival of both groups according to the presence or absence of PPI.MethodsThis single-center, retrospective, observational study examined data from MEV and SEV groups comprising 92 and 373 patients, respectively. The mean clinical follow-up was 2.5 ± 1.7 years. Mortality information was obtained from the National Institutes of Health Information and Statistics.ResultsBaseline characteristics were comparable between the groups. The log-rank test showed higher cardiovascular mortality in the MEV group [p=0.042; RR: 1.594 (95%CI: 1.013-2.508)]. The Cox proportional hazards model identified MEV implantation as an independent predictor of cardiovascular mortality. The rate of PPI was twice as high in the MEV versus SEV group (33.7% vs. 16.1%;p<0.001). We compared the survival of both groups according to the presence or absence of PPI and found higher mortality in the MEV group without PPI versus the SEV group without PPI (p=0.007; RR: 2.156 [95%CI: 1.213-3.831]). Survival did not differ in the groups with PPI.ConclusionsA higher mid-term cardiovascular mortality rate was observed with MEV versus SEV implants. Comparing both groups according to the presence or absence of PPI, we observed a higher mortality risk in patients with MEV without PPI than in SEV without PPI. In contrast, mortality did not differ between the groups when PPI was implanted.What is already known on this topicUse of the mechanically expandable transcatheter aortic valve (MEV) has been recently linked to increased risks of valve dysfunction and cardiovascular mortality. The risk of developing conduction disturbance with the MEV valve is well-known, and the negative prognostic impact of permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation is another consideration.What this study addsOur study suggested that higher cardiovascular mortality was independently associated with the use of MEV versus self-expandable valves (SEV) implants. Comparing both groups according to the presence or absence of PPI, we observed a higher mortality risk in patients with MEV without PPI than in those with SEV without PPI.How this study might affect research, practice or policyAlthough MEV were recalled in 2020, thousands of patients have been treated with them. Therefore, patients with MEV without PPI deserve increased attention during long-term follow-up.
Subtyping strokes using blood-based biomarkers: A proteomics approach
Authors: Misra Shubham , Singh Praveen , Sengupta Shantanu , Kushwaha Manoj , Rahman Zuhaibur , Bhalla Divya , Talwar Pumanshi , Nath Manabesh , Chakraborty Rahul , Kumar Pradeep , Kumar Amit , Aggarwal Praveen , Srivastava Achal K , Pandit Awadh K , Mohania Dheeraj , Prasad Kameshwar , Vibha Deepti 
Published: June 2023

AbstractBackground and Objectives:Rapid diagnosis of stroke and its subtypes is critical in early stages. We aimed to discover and validate blood-based protein biomarkers to differentiate ischemic stroke (IS) from intracerebral hemorrhage (ICH) within 24 hours using high-throughput proteomics.Methods:We collected serum samples within 24 hours from acute stroke (IS & ICH) and mimics patients. In the discovery phase, SWATH-MS proteomics identified differentially expressed proteins (fold change: 1.5, p<0.05, and confirmed/tentative selection using Boruta random forest) between IS and ICH which were validated using Multiple Reaction Monitoring (MRM) proteomics in the validation phase. Protein-protein interactions and pathway analysis were conducted using STRING version 11 and Cytoscape 3.9.0. Cut-off points were determined using Youden Index. Prediction models were developed using backward stepwise multivariable logistic regression analysis. Hanley-McNeil test, Integrated discrimination improvement index, and likelihood ratio test determined the improved discrimination ability of biomarkers added to clinical models.Results:Discovery phase included 20 IS and 20 ICH while validation phase included 150 IS, 150 ICH, and 6 stroke mimics. We quantified 365 proteins in the discovery phase. Between IS and ICH, we identified 20 differentially expressed proteins. In the validation phase, combined prediction model including three biomarkers: GFAP (OR 0.04; 95%CI 0.02-0.11), MMP9 (OR 0.09; 95%CI 0.03-0.28), APO-C1 (OR 5.76; 95%CI 2.66-12.47) and clinical variables independently differentiated IS from ICH (accuracy: 92%, sensitivity: 96%, specificity: 69%). Addition of biomarkers to clinical variables improved the discrimination capacity by 26% (p<0.001). Subgroup analysis within 6 hours identified that GFAP and MMP9 differentiated IS from ICH with a sensitivity> 90%.Conclusions:Our study identified that GFAP, MMP, and APO-C1 biomarkers independently differentiated IS from ICH within 24 hours and significantly improved the discrimination ability to predict IS. Temporal profiling of these biomarkers in the acute phase of stroke is urgently warranted.
Evolution of chromosome arm aberrations in breast cancer through genetic network rewiring
Authors: Kuzmin Elena , Baker Toby M. , Lesluyes Tom , Monlong Jean , Abe Kento T. , Coelho Paula P. , Schwartz Michael , Zou Dongmei , Morin Genevieve , Pacis Alain , Yang Yang , Martinez Constanza , Barber Jarrett , Kuasne Hellen , Li Rui , Bourgey Mathieu , Fortier Anne-Marie , Davison Peter G. , Omeroglu Atilla , Guiot Marie-Christine , Morris Quaid , Kleinman Claudia L. , Huang Sidong , Gingras Anne-Claude , Ragoussis Jiannis , Bourque Guillaume , Van Loo Peter , Park Morag 
Published: June 2023

AbstractThe basal breast cancer subtype is enriched for triple-negative breast cancer (TNBC) and displays consistent large chromosomal deletions. Here, we characterize the evolution and maintenance of chromosome 4p (chr4p) loss in basal breast cancer. TCGA data analysis showed recurrent deletion of chr4p in basal breast cancer. Phylogenetic analysis of a unique panel of 23 primary tumor/patient-derived xenograft basal breast cancers revealed early evolution of chr4p deletion. Mechanistically we show that Chr4p loss is associated with enhanced proliferation. Gene function studies identified an unknown gene,C4orf19,within chr4p, which suppressed proliferation when overexpressed and is a novel member of a PDCD10-GCKIII kinase module, we name asPGCA1. Genome-wide pooled overexpression screens using a barcoded library of human open reading frames, identified chromosomal regions, including chr4p, that suppress proliferation when overexpressed in a context-dependent manner implicating network interactions. Together this sheds light on the early emergence of complex aneuploid karyotypes involving chr4p and adaptive landscapes shaping breast cancer genomes.
Decoded EEG Neurofeedback-Guided Cognitive Reappraisal Training for Emotion Regulation
Authors: Li Linling , Gui Xueying , Huang Gan , Zhang Li , Han Xue , Liang Zhen , Zhang Zhiguo 
Published: June 2023

AbstractNeurofeedback is an innovative self-training that adjusts and enhances brain function. One of the more studied application scenarios with neurofeedback training is emotion regulation. Compared with regional brain activity-informed neurofeedback techniques, neurofeedback protocols using the decoded brain states as feedback signals could make the setting of regulation targets more specific and objective. In the present study, we constructed an EEG neurofeedback-guided cognitive reappraisal training protocol for emotion regulation. Forty-two healthy participants (20 females; 22.4±2.2 years old) were recruited and were randomly assigned to either the neurofeedback group or the control group. During the training process, we calculate the real-time self-regulation performance on the evoked emotion based on the decoded emotional states and fed it back to the subjects as the feedback signal. According to our results, real-time feedback of the regulation effect helps subjects improve emotion regulation performance for emotional stimuli with low positive valence. Further analysis of selected EEG features for emotion classification revealed the neural correlates with neurofeedback training. This newly proposed neurofeedback training protocol is a promising treatment for emotion-related mental disorders, with the potential to be a low-cost and high-portability brain-based, non-invasive, neural modulation technique.
A subtle structural modification of a synthetic cannabinoid receptor agonist drastically increases its efficacy at the CB1 receptor
Authors: Yano Hideaki , Chitsazi Rezvan , Lucaj Christopher , Tran Phuong , Hoffman Alexander F. , Baumann Michael H. , Lupica Carl R. , Shi Lei 
Published: June 2023

ABSTRACTThe emergence of synthetic cannabinoid receptor agonists (SCRAs) as illicit psychoactive substances has posed considerable public health risks that include fatalities. Many SCRAs exhibit much higher efficacy and potency, compared with the phytocannabinoid Δ9-tetrahydrocannabinol (THC), at the cannabinoid receptor 1 (CB1R), a G protein-coupled receptor involved in modulating neurotransmitter release. In this study, we investigated structure activity relationships (SAR) of aminoalkylindole SCRAs at CB1Rs, focusing on 5F-pentylindoles containing an amide linker attached to different head moieties. Usingin vitrobioluminescence resonance energy transfer (BRET) assays, we identified a few of SCRAs exhibiting significantly higher efficacy in engaging the Gi protein and recruiting β-arrestin than the reference CB1R full agonist CP55940. Importantly, adding a methyl group at the head moiety of 5F-MMB-PICA yielded 5F-MDMB-PICA, an agonist exhibiting a large increase in efficacy and potency at the CB1R. This pharmacological observation was supported by a functional assay of the effects of these SCRAs on glutamate field potentials recorded in hippocampal slices. Molecular modeling and simulations of the CB1R bound with either of the SCRAs revealed critical structural determinants contributing to the higher efficacy of 5F-MDMB-PICA, and how these subtle differences propagated to the receptor-G protein interface. Thus, we find that apparently minor structural changes in the head moiety of SCRAs can cause major changes in efficacy. Our results highlight the need for close monitoring of structural modifications of newly emerging SCRAs and their potential for toxic drug responses in humans.
Impaired motor-to-sensory transformation mediates auditory hallucinations
Authors: Yang Fuyin , Zhu Hao , Cao Xinyi , Li Hui , Fang Xinyu , Yu Lingfang , Li Siqi , Wu Zenan , Li Chunbo , Zhang Chen , Tian Xing 
Published: June 2023

AbstractDistinguishing reality from hallucinations requires efficient monitoring of agency. It has been hypothesized that a copy of motor signals, termedefference copy (EC) or corollary discharge (CD), suppresses sensory responses to yield a sense of agency; impairment of the inhibitory function leads to hallucinations. However, how can the sole absence of inhibition yield positive symptoms of hallucinations? We hypothesize that selective impairments in functionally distinct signals ofCDandECduring motor-to-sensory transformation cause the positive symptoms of hallucinations. In an electroencephalography (EEG) experiment with a delayed articulation paradigm in schizophrenic patients with (AVHs) and without auditory verbal hallucinations (non-AVHs), we found that preparing to speak without knowing the contents (general preparation) did not suppress auditory responses in both patient groups, suggesting the absent of inhibitory function ofCD. Whereas, preparing to speak a syllable (specific preparation) enhanced the auditory responses to the prepared syllable in non-AVHs, whereas AVHs showed enhancement in responses to unprepared syllables, opposite to the observations in the normal population, suggesting that the enhancement function ofECis not precise in AVHs. A computational model with a virtual lesion of an inhibitory inter-neuron and disproportional sensitization of auditory cortices fitted the empirical data and further quantified the distinct impairments in motor-to-sensory transformation in AVHs. These results suggest that ‘broken’CDplus ‘noisy’ECcauses erroneous monitoring on the imprecise generation of internal auditory representation and yields auditory hallucinations. Specific impairments in functional granularity of motor-to-sensory transformation mediate positivity symptoms of agency abnormality in mental disorders.