bluuebunny/crossref_metadata_2025_split huggingface dataset:
An associative transcriptomics study on rice bean (Vigna umbellata) provides new insights into genetic basis and candidate genes governing flowering, maturity and seed weight
Authors: Sahu Tanmaya Kumar , Verma Sachin Kumar , Gayacharan  , Singh Nagendra Pratap , Joshi Dinesh Chandra , Wankhede D. P. , Singh Mohar , Bhardwaj Rakesh , Parida Swarup Kumar , Chattopadhyay Debasis , Singh Gyanendra Pratap , Singh Amit Kumar 
Published: February 2023

AbstractRice bean is an underrated legume with significant potential to support food and nutritional security worldwide, being a rich source of proteins, minerals, and essential fatty acids. Therefore, we considered three pivotal production traits of rice bean; flowering, maturity and seed weight, to identify associated candidate genes. One-hundred diverse genotypes out of 1800 evaluated rice bean accessions from the Indian National Genebank were considered for phenotypic data collection and genotyping by transcriptome sequencing approach. Association analysis involving various GWAS models was conducted to identify significant marker-trait associations. The results revealed association of 82 markers on 48 transcripts for flowering, 26 markers on 22 transcripts for maturity and 22 markers on 21 transcripts for seed weight. The annotation of associated transcripts unraveled the functional genes related to the considered traits. Among the significant candidate genes identified, HSC80, P-II PsbX, phospholipid-transporting-ATPase-9, pectin-acetylesterase-8 and E3-ubiquitin-protein-ligase-RHG1A were found associated with flowering. Further, associations of WRKY1 and DEAD-box-RH27 with seed weight, PIF3 and pentatricopeptide-repeat-containing-gene with maturity & seed weight and aldo-keto-reductase with flowering & maturity have been revealed. The present investigation provides insights into the genetic mechanisms governing economically-essential traits like flowering, maturity and seed weight that can be potentially utilized for rice bean improvement.HighlightsThe present investigation is the first associative transcriptomics approach implemented onVigna umbellata. Based on the marker-trait association analysis, candidate genes for flowering, maturity and seed weight traits are reported.
Dissecting durum wheat time to anthesis into physiological traits using a QTL-based model
Authors: Martre Pierre , Motzo Rosella , Mastrangelo Anna Maria , Marone Daniela , De Vita Pasquale , Giunta Francesco 
Published: February 2023

AbstractFine tuning crop development is a major breeding avenue to increase crop yield and for adaptation to climate change. In this study, we used a model that integrates our current understanding of the physiology of wheat phenology to predict the development and anthesis date of a RILs population of durum wheat with genotypic parameters controlling vernalization requirement, photoperiod sensitivity, and earlinessper seestimated using leaf stage, final leaf number, anthesis date data from a pot experiment with vernalized and nonvernalized treatments combined with short- and long-day length. Predictions of final leaf number and anthesis date of the QTL-based model was evaluated for the whole population of RILs in a set of independent field trials and for the two parents, which were not used to estimate the parameter values. Our novel approach reduces the number of environments, experimental costs, and the time required to obtain the required data sets to develop a QTL-based prediction of model parameters. Moreover, the use of a physiologically based model of phenology gives new insight into genotype-phenology relations for wheat. We discuss the approach we used to estimate the parameters of the model and their association with QTL and major phenology genes that collocate at QTL.HighlightWe used a modeling framework integrating our current understanding of the physiology of wheat phenology to dissect durum wheat time to anthesis into physiological traits and link them to QTL.
Transcription elongation defects link oncogenic splicing factor mutations to targetable alterations in chromatin landscape
Authors: Boddu Prajwal C , Gupta Abhishek , Roy Rahul , De La Pena Avalos Barbara , Herrero Ane Olazabal , Neuenkirchen Nils , Zimmer Josh , Chandhok Namrata , King Darren , Nannya Yashuhito , Ogawa Seishi , Lin Haifan , Simon Matthew , Dray Eloise , Kupfer Gary , Verma Amit K. , Neugebauer Karla M. , Pillai Manoj M 
Published: February 2023

ABSTRACTTranscription and splicing of pre-messenger RNA are closely coordinated, but how this functional coupling is disrupted in human disease remains unexplored. Here, we investigated the impact of non-synonymous mutations in SF3B1 and U2AF1, two commonly mutated splicing factors in cancer, on transcription. We find that the mutations impair RNA Polymerase II (RNAPII) transcription elongation along gene bodies leading to transcription-replication conflicts, replication stress and altered chromatin organization. This elongation defect is linked to disrupted pre-spliceosome assembly due to impaired association of HTATSF1 with mutant SF3B1. Through an unbiased screen, we identified epigenetic factors in the Sin3/HDAC complex, which, when modulated, normalize transcription defects and their downstream effects. Our findings shed light on the mechanisms by which oncogenic mutant spliceosomes impact chromatin organization through their effects on RNAPII transcription elongation and present a rationale for targeting the Sin3/HDAC complex as a potential therapeutic strategy.GRAPHICAL ABSTRACTHIGHLIGHTS-Oncogenic mutations of SF3B1 and U2AF1 cause a gene-body RNAPII elongation defect-RNAPII transcription elongation defect leads to transcription replication conflicts, DNA damage response, and changes to chromatin organization and H3K4me3 marks-The transcription elongation defect is linked to disruption of the early spliceosome formation through impaired interaction of HTATSF1 with mutant SF3B1.-Changes to chromatin organization reveal potential therapeutic strategies by targeting the Sin3/HDAC pathway
Modelling red blood cell optical trapping by machine learning improved geometrical optics calculations
Authors: Tognato R. , Ciriza D. Bronte , Maragò O. M. , Jones P. H. 
Published: February 2023

AbstractOptically trapping red blood cells allows to explore their biophysical properties, which are affected in many diseases. However, because of their nonspherical shape, the numerical calculation of the optical forces is slow, limiting the range of situations that can be explored. Here we train a neural network that improves both the accuracy and the speed of the calculation and we employ it to simulate the motion of a red blood cell under different beam configurations. We found that by fixing two beams and controlling the position of a third, it is possible to control the tilting of the cell. We anticipate this work to be a promising approach to study the trapping of complex shaped and inhomogeneous biological materials, where the possible photodamage imposes restrictions in the beam power.
Sex-dimorphic expression of extracellular matrix genes in mouse bone marrow neutrophils
Authors: McGill Cassandra J. , Ewald Collin Y. , Benayoun Bérénice A. 
Published: February 2023

AbstractThe mammalian innate immune system is sex-dimorphic. Neutrophils are the most abundant leukocyte in humans and represent innate immunity’s first line of defense. We previously found that primary mouse bone marrow neutrophils show widespread sex-dimorphism throughout life, including at the transcriptional level. Extracellular matrix [ECM]-related terms were observed among the top sex-dimorphic genes. Since the ECM is emerging as an important regulator of innate immune responses, we sought to further investigate the transcriptomic profile of primary mouse bone marrow neutrophils at both the bulk and single-cell level to understand how biological sex may influence ECM component expression in neutrophils throughout life. Here, using curated gene lists of ECM components and unbiased weighted gene co-expression network analysis [WGCNA], we find that multiple ECM-related gene sets show widespread female-bias in expression in primary mouse neutrophils. Since many immune-related diseases (e.g., rheumatoid arthritis) are more prevalent in females, our work may provide insights into the pathogenesis of sex-dimorphic inflammatory diseases.
Atypical Chemokine Receptor 3 ‘Senses’ CXC Chemokine Receptor 4 Activation Through GPCR Kinase Phosphorylation
Authors: Schafer Christopher T. , Chen Qiuyan , Tesmer John J. G. , Handel Tracy M. 
Published: February 2023

AbstractAtypical chemokine receptor 3 (ACKR3) is an arrestin-biased receptor that regulates extracellular chemokine levels through scavenging. The scavenging action mediates the availability of the chemokine CXCL12 for the G protein-coupled receptor (GPCR) CXCR4 and requires phosphorylation of the ACKR3 C-terminus by GPCR kinases (GRKs). ACKR3 is phosphorylated by GRK2 and GRK5, but the mechanisms by which these kinases regulate the receptor are unresolved. Here we mapped the phosphorylation patterns and determined that GRK5 phosphorylation of ACKR3 dominates β-arrestin recruitment and chemokine scavenging over GRK2. Co-activation of CXCR4 significantly enhanced phosphorylation by GRK2 through the liberation of Gβγ. These results suggest that ACKR3 ‘senses’ CXCR4 activation through a GRK2-dependent crosstalk mechanism. Surprisingly, we also found that despite the requirement for phosphorylation, and the fact that most ligands promote β-arrestin recruitment, β-arrestins are dispensable for ACKR3 internalization and scavenging, suggesting a yet to be determined function for these adapter proteins.
BCAT1 inhibition affects CD8+T cell activation, exhaustion, and tumoral immunity by altering iron homeostasis
Authors: Lodi Francesca , Certo Michelangelo , Elkafrawy Hagar , Li Weixing , Vu Hong A. , Gilbo Konstantin , Su Li , Pegg Ian L. , Weiss Tobias , Bühler Marcel , Weller Michael , Yeh Charles , Corn Jacob E. , Park Kwon-Sik , Ko Jeong-Hun , Behmoaras Jacques , Mauro Claudio , Lambrechts Diether , Papathanassiu Adonia E. 
Published: February 2023

ABSTRACTThe present study explores the role of the cytosolic branched chain amino acid aminotransferase (BCAT1) in CD8+T cell activation, in general, and tumor immunity, in particular, and identifies a non-canonical function of the protein in iron homeostasis. Pharmacologic inhibition of BCAT1 using the novel drug ERG245 abrogates the effector functions of CD8+T cells in vitro and metabolically reprograms the cells towards increased OXPHOS. In vivo, it suppresses activation of CD8+T cells in DSS colitis leading to improved disease outcomes. Remarkably, withdrawal of BCAT1 inhibition further amplifies OXPHOS and gives rise to CD8+T cells with increased cytotoxicity in vitro and in vivo. When combined with an anti-PD-1 treatment, temporal BCAT1 inhibition dramatically increases anti-PD-1 efficacy inducing complete and durable tumor regressions in the moderately immunogenic CT26 tumor model. Single cell RNA-seq data link expression of Bcat genes to exhausted T cells within the tumor microenvironment of human cancer patients, whereas in vitro assays indicate that BCAT1 inhibition partially prevents the adoption of a terminally exhausted phenotype by CD8+T cells. We propose BCAT1 as a target for cancer combinatory therapies.SIGNIFICANCEThe study explores for the first time the role of BCAT1 in CD8+T cell activation and proposes novel strategies for using BCAT1 inhibitors in cancer and beyond. It demonstrates that BCAT1 exerts its function without significantly altering branched chain amino acid (BCAA) levels through a mechanism that controls iron homeostasis, a novel non-canonical mechanism of action, and implicates BCAT1 in the adoption of an exhausted phenotype by T cells found in human cancers. While the majority of metabolic drugs temper OXPHOS, it demonstrates that an agent that increases OXPHOS in CD8+T cells can be used successfully as an immune-oncology drug.
Rescue of Auditory Function by a Single Administration of AAV-TMPRSS3Gene Therapy in Aged Mice of Human Recessive Deafness DFNB8
Authors: Du Wan , Ergin Volkan , Loeb Corena , Huang Mingqian , Silver Stewart , Armstrong Ariel Miura , Huang Zaohua , Gurumurthy Channabasavaiah B. , Staecker Hinrich , Liu Xuezhong , Chen Zheng-Yi 
Published: February 2023

AbstractsPatients with mutations in theTMPRSS3gene suffer from recessive deafness DFNB8/DFNB10 for whom cochlear implantation is the only treatment option. Poor cochlear implantation outcomes are seen in some patients. To develop biological treatment for TMPRSS3 patients, we generated a knock-in mouse model with a frequent human DFNB8TMPRSS3mutation. TheTmprss3A306T/A306Thomozygous mice display delayed onset progressive hearing loss similar to human DFNB8 patients. Using AAV2 as a vector to carry a humanTMPRSS3gene, AAV2-hTMPRSS3injection in the adult knock-in mouse inner ears results inTMPRSS3expression in the hair cells and the spiral ganglion neurons. A single AAV2-hTMPRSS3injection in agedTmprss3A306T/A306Tmice leads to sustained rescue of the auditory function, to a level similar to the wildtype mice. AAV2-hTMPRSS3delivery rescues the hair cells and the spiral ganglions. This is the first study to demonstrate successful gene therapy in an aged mouse model of human genetic deafness. This study lays the foundation to develop AAV2-hTMPRSS3gene therapy to treat DFNB8 patients, as a standalone therapy or in combination with cochlear implantation.
Domains Required for FRQ-WCC Interaction within the Core Circadian Clock ofNeurospora
Authors: Wang Bin , Dunlap Jay C. 
Published: February 2023

AbstractIn the negative feedback loop composing theNeurosporacircadian clock, the core element, FREQUENCY (FRQ) binds with FRH (FRQ-interacting RNA helicase) and Casein Kinase 1 (CK1) to form the FRQ-FRH complex (FFC) which represses its own expression by interacting with and promoting phosphorylation of its transcriptional activators White Collar-1 (WC-1) and WC-2 (together forming the White Collar Complex, WCC). Physical interaction between FFC and WCC is a prerequisite for the repressive phosphorylations, and although the motif on WCC needed for this interaction is known, the reciprocal recognition motif(s) on FRQ remains poorly defined. To address this, FFC-WCC was assessed in a series offrqsegmental-deletion mutants, confirming that multiple dispersed regions on FRQ are necessary for its interaction with WCC. Biochemical analysis shows that interaction between FFC and WCC but not within FFC or WCC can be disrupted by high salt, suggesting that electrostatic forces drive the association of the two complexes. As a basic sequence on WC-1 was previously identified as a key motif for WCC-FFC assembly, our mutagenetic analysis targeted negatively charged residues of FRQ leading to identification of three Asp/Glu clusters in FRQ that are indispensable for FFC-WCC formation. Surprisingly, in severalfrqAsp/Glu-to-Ala mutants that vastly diminish FFC-WCC interaction, the core clock still oscillates robustly with an essentially WT period, indicating that the binding strength between the positive and negative elements in the feedback loop is required for the clock but is not a determinant of the period length.
Tight hydrophobic core and flexible helices yield MscL with a high tension gating threshold and a membrane area mechanical strain buffer
Authors: Sharma Arjun , Anishkin Andriy , Sukharev Sergei , Vanegas Juan M. 
Published: February 2023

ABSTRACTThe mechanosensitive (MS) channel of large conductance, MscL, is the high-tension threshold osmolyte release valve that limits turgor pressure in bacterial cells in the event of drastic hypoosmotic shock. Despite MscL fromM. tuberculosis(TbMscL) being the first structurally characterized MS channel, its protective mechanism of activation at nearly-lytic tensions has not been fully understood. Here, we describe atomistic simulations of expansion and opening of wild-type (WT) TbMscL in comparison with five of its gain-of-function (GOF) mutants. We show that under far-field membrane tension applied to the edge of the periodic simulation cell, WT TbMscL expands into a funnel-like structure with trans-membrane helices bent by nearly 70 degrees, but does not break its ‘hydrophobic seal’ within extended 20 μs simulations. GOF mutants carrying hydrophilic substitutions in the hydrophobic gate of increasing severity (A20N, V21A, V21N, V21T and V21D) also quickly transition into funnel-shaped conformations but subsequently fully open within 1-8 us. This shows that solvation of the de-wetted (vapor-locked) constriction is the rate-limiting step in the gating of TbMscL preceded by area-buffering silent expansion. Pre-solvated gates in severe V21N and V21D mutants eliminate this barrier. We predict that the asymmetric shape-change of the periplasmic side of the channel during the silent expansion provides strain-buffering to the outer leaflet thus re-distributing the tension to the inner leaflet, where the gate resides.
Frequency of nursing student medication errors: A systematic review
Authors: Triantafyllou Christos , Gamvrouli Maria , Myrianthefs Pavlos 
Published: February 2023

ABSTRACTIntroductionHealth promotion and patient safety are the main targets of the healthcare provision by the National Health Systems. As for the nursing profession, nursing students make medication errors during clinical interventions, which could be a potential danger to patient safety.AimThe investigation of the frequency of nursing student medication errors, as well as the frequency of each type of nursing student medication errors.MethodsA systematic review of the literature was conducted on the electronic database “PubMed” with the keywords: “medication error”, “prescribing error”, “drug error”, “drug use error”, “drug mistake”, “wrong drug”, “wrong dose”, “administration error”, “dispensing error”, “incorrect drug”, “incorrect dose”, “inappropriate prescribing”, “inappropriate medication”, “transcription error”, “nursing student”, “nursing trainee” and on the Greek electronic database IATROTEK-online with the keywords: “medication errors” and “nursing students”, without time limit for the publication of scientific papers. On PubMed, the keywords were searched in the title and abstract of the studies. Studies were excluded if they were not published in English and Greek language, were conducted on animals, and were case studies, editorials, and letters to the editor.ResultsOf the 47 scientific papers retrieved, 6 were included in the systematic review. A total of 1,904 nursing student medication errors were recorded by nursing students. The majority of errors were: 1) wrong dose form (330,17%), 2) omission error (313, 16.4%), and 3) wrong time (259, 13.6%).ConclusionsThe frequency of nursing student medication errors is high. The safe administration of medications is an important skill that nursing students should learn. At a theoretical and practical/clinical level, it would be advisable for clinical nurses and academics to jointly develop an educational program to acquire correct knowledge and perceptions regarding safe medication administration.
Potential for person-to-person transmission of henipaviruses: A systematic review of the literature
Authors: Hegde Sonia , Lee Kyu Han , Styczynski Ashley , Jones Forrest K , Gomes Isabella , Das Pritimoy , Gurley Emily S. 
Published: February 2023

AbstractNipah virus – Bangladesh (NiVB) is a bat-borne zoonosis transmitted between people through the respiratory route, posing a pandemic risk. The risk posed by related henipaviruses, including Hendra virus (HeV) and Nipah virus – Malaysia (NiVM) is less clear. We conducted a broad search of the literature encompassing both human infections and animal models to synthesize evidence about potential for person-to-person spread of these henipaviruses. More than 600 human infections have been reported in the literature, but information about biological processes related to transmission is limited; information on viral shedding was only available for 40 case-patients. There is substantial evidence demonstrating person-to-person transmission of NiVB, though there is also evidence that NiVMhas been transmitted from person to person. Less direct evidence is available about the risk for person-to-person transmission of HeV, but animals infected with HeV shed more virus in the respiratory tract than those infected with NiVMsuggesting potential for transmission. As the family of known henipaviruses continues to grow, shared protocols for conducting and reporting from human investigations and animal experiments are urgently needed to advance our understanding of transmission risk.
Leading and Following: Noise Differently Affects Semantic and Acoustic Processing during Naturalistic Speech Comprehension
Authors: Zhang Xinmiao , Li Jiawei , Li Zhuoran , Hong Bo , Diao Tongxiang , Ma Xin , Nolte Guido , Engel Andreas K. , Zhang Dan 
Published: February 2023

AbstractDespite the distortion of speech signals caused by unavoidable noise in daily life, our ability to comprehend speech in noisy environments is relatively stable. However, the neural mechanisms underlying reliable speech-in-noise comprehension remain to be elucidated. The present study investigated the neural tracking of acoustic and semantic speech information during noisy naturalistic speech comprehension. Participants listened to narrative audio recordings mixed with spectrally matched stationary noise at three signal-to-ratio (SNR) levels (no noise, 3 dB, -3 dB), and 60-channel electroencephalography (EEG) signals were recorded. A temporal response function (TRF) method was employed to derive event-related-like responses to the continuous speech stream at both the acoustic and the semantic levels. Whereas the amplitude envelope of the naturalistic speech was taken as the acoustic feature, word entropy and word surprisal were extracted via the natural language processing method as two semantic features. Theta-band frontocentral TRF responses to the acoustic feature were observed at around 400 ms following speech fluctuation onset over all three SNR levels, and the response latencies were more delayed with increasing noise. Delta-band frontal TRF responses to the semantic feature of word entropy were observed at around 200 to 600 ms leading to speech fluctuation onset over all three SNR levels. The response latencies became more leading with increasing noise and were correlated with comprehension performance and perceived speech intelligibility. While the following responses to speech acoustics were consistent with previous studies, our study revealed the robustness of leading responses to speech semantics, which suggests a possible predictive mechanism at the semantic level for maintaining reliable speech comprehension in noisy environments.HighlightsLeading responses were observed in the semantic-level neural tracking, with more leading latencies as noise increased.Following responses were observed in the acoustic-level neural tracking, with more delayed latencies as noise increased.Semantic-level neural tracking is correlated with comprehension performance and perceived intelligibility.Distinct frequency bands were involved in speech semantic and acoustic processing.