bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic and Genetic Insights into Mendel’s Pea Genes
Authors: Feng Cong , Chen Baizhi , Hofer Julie , Shi Yan , Jiang Mei , Song Bo , Cheng Hong , Lu Lu , Wang Luyao , Howard Alex , Bendahmane Abdel , Fouchal Anissa , Moreau Carol , Sawada Chie , LeSignor Christine , Vikeli Eleni , Tsanakas Georgios , Zhao Hang , Cheema Jitender , Barclay J. Elaine , Sayers Liz , Wingen Luzie , Vigouroux Marielle , Vickers Martin , Ambrose Mike , Dalmais Marion , Higuera-Poveda Paola , Spanner Rebecca , Horler Richard , Wouters Roland , Chundakkad Smitha , Zhao Xiaoxiao , Li Xiuli , Sun Yuchen , Huang Zejian , Deng Xing Wang , Steuernagel Burkhard , Domoney Claire , Ellis Noel , Chayut Noam , Cheng Shifeng 
Published: June 2024

ABSTRACTPea,Pisum sativum, is an excellent model system through which Gregor Mendel established the foundational principles of inheritance. Surprisingly, till today, the molecular nature of the genetic differences underlying the seven pairs of contrasting traits that Mendel studied in detail remains partially understood. Here, we present a genomic and phenotypic variation map, coupled with haplotype-phenotype association analyses across a wide range of traits in a globalPisumdiversity panel. We focus on a genomics-enabled genetic dissection of each of the seven traits Mendel studied, revealing many previously undescribed alleles for the four characterized genes,R,Le,IandA, and elucidating the gene identities and mutations for the remaining three uncharacterized traits. Notably, we identify: (1) a ca. 100kb deletion upstream of theChlorophyll synthase(ChlG) gene, which generates aberrant transcripts and confers the yellow pod phenotype ofgpmutants; (2) an in-frame premature stop codon mutation in a Dodeca-CLE41/44 signalling peptide which explains the parchmentless mutant phenotype corresponding top; and (3) a 5bp in-frame deletion in aCIK-likereceptor kinase gene corresponding to the fasciated stem phenotypefa, which Mendel described in terms of flower position, and we postulate the existence of aModifier of fa(Mfa) locus that masks this meristem defect. Mendel noted the pleiotropy of theamutation, including inhibition of axil ring anthocyanin pigmentation, a trait we found to be controlled by allelic variants of the geneDwithin anR2R3-MYBgene cluster. Furthermore, we characterize and validate natural variation of a quantitative genetic locus governing both pod width and seed weight, characters that Mendel deemed were not sufficiently demarcated for his analyses. This study establishes a cornerstone for fundamental research, education in biology and genetics, and pea breeding practices.
Tendon Inversion Improves Tendon-to-Bone Healing in a Rat Bicep Tenodesis Model
Authors: Cong Ting , Li Thomas M. , Buller Dustin C. , Arvind Varun , Nasser Philip , Laudier Damien M. , Ferlauto Harrison R. , Hall Arielle J. , Li Deborah M. , Huang Alice H. , Cagle Paul J. , Galatz Leesa M. , Hausman Michael R. 
Published: June 2024

AbstractPurposeTendon- or ligament-to-bone repair remains a surgical challenge. While bone tunnel fixation is a common surgical technique whereby soft tissue is expected to heal against a bone tunnel interface, contemporary methods have yet to recapitulate biomechanical similarity to the native enthesis. In this study, we aim to demonstrate that inside-out longitudinal tendon inversion may improve bone tunnel healing with the hypothesis that inversion removes the gliding epitenon surface from the healing interface thereby improving tunnel interface healing.Methods40 male Sprague-Dawley rats underwent either native tendon tenodesis (control group) or tendon inversion tenodesis (experimental group). Interface tissue was harvested 8 weeks post-operatively. Biomechanical testing was performed to assess tensile strength and modes of failure. Histology was performed to assess tissue architecture, and immunohistochemistry was used confirmed abrogation of epitendinous lubricin from interface tissue.ResultsNeither surgical intervention led to discernible adverse effects on animal health. Maximum tensile strength increased after tendon inversion compared to control surgery. The extracellular matrix protein lubricin was reduced with tendon inversion, and specimens with tendon inversion had greater healing scores and collagen fibril alignment at the healing interface.ConclusionsTendon inversion improves bone tunnel healing in rats.Clinical RelevanceOur findings suggest that longitudinal tendon inversion, or inverse tubularization, in a rat biceps tenodesis model improves tendon-to-bone healing in part due to disruption of the epitendinous surface at the bone healing interface. This work provides molecular insight into future improvements for tendon-to-bone repair surgical techniques.
Comparative population genomics unveils congruent secondary suture zone in Southwest Pacific Hydrothermal Vents
Authors: Tran Lu Y Adrien , Ruault Stéphanie , Daguin-Thiébaut Claire , Le Port Anne-Sophie , Ballenghien Marion , Castel Jade , Gagnaire Pierre-Alexandre , Bierne Nicolas , Arnaud-Haond Sophie , Poitrimol Camille , Thiébaut Eric , Lallier François H , Broquet Thomas , Jollivet Didier , Bonhomme François , Hourdez Stéphane 
Published: June 2024

AbstractHow the interplay of biotic and abiotic factors shapes current genetic diversity at the community level remains an open question, particularly in the deep sea. Comparative phylogeography of multiple species can reveal the influence of past climatic events, geographic barriers, and species life history traits on spatial patterns of genetic structure across lineages.To shed light on the factors that shape community-level genetic variation and to improve our understanding of deep-sea biogeographic patterns, we conducted a comparative population genomics study on seven hydrothermal vent species co-distributed in the Back-Arc Basins (BABs) of the Southwest Pacific region. Using ddRAD-seq, we compared the range-wide distribution of genomic diversity across species and discovered a shared phylogeographic break. Demogenetic inference revealed shared histories of lineage divergence and a secondary contact. Low levels of asymmetric gene flow probably occurred in most species between the Woodlark and North Fiji basins, but the exact location of contact zones varied from species to species. For two species, we found individuals from the two lineages co-occurring in sympatry in Woodlark Basin. Although species exhibit congruent patterns of spatial structure (Eastern vs Western sites), they also show variation in the degree of divergence among lineages across the suture zone. Our results also show heterogeneous gene flow across the genome, indicating possible partial reproductive isolation between lineages and early speciation.Our comparative study highlights the pivotal role of historical and contemporary factors, underscoring the need for a comprehensive approach—especially in addressing knowledge gaps on the life history traits of deep-sea species.
MAPK13 controls structural remodeling and disease after epithelial injury
Authors: Wu Kangyun , Zhang Yong , Mao Dailing , Iberg Courtney A. , Yin-Declue Huiqing , Sun Kelly , Keeler Shamus P. , Wikfors Hallie A. , Young Deanna , Yantis Jennifer , Austin Stephen R. , Byers Derek E , Brody Steven L. , Crouch Erika C. , Romero Arthur G. , Holtzman Michael J. 
Published: June 2024

AbstractAll living organisms are charged with repair after injury particularly at epithelial barrier sites, but in some cases this response leads instead to structural remodeling and long-term disease. Identifying the molecular and cellular control of this divergence is key to disease modification. In that regard, stress kinase control of epithelial stem cells is a rational entry point for study. Here we examine the potential for mitogen-activated protein kinase 13 (MAPK13) regulation of epithelial stem cells using models of respiratory viral injury and post-viral lung disease. We show thatMapk13gene-knockout mice handle acute infectious illness as expected but are protected against structural remodeling manifest as basal-epithelial stem cell (basal-ESC) hyperplasia-metaplasia, immune activation, and mucinous differentiation. In corresponding cell models,Mapk13-deficiency directly attenuates basal-ESC growth and organoid formation. Extension to human studies shows marked induction/activation of basal-cell MAPK13 in clinical samples of comparable remodeling found in asthma and COPD. Here again,MAPK13gene-knockdown inhibits human basal-ESC growth in culture. Together, the data identify MAPK13 as a control for structural remodeling and disease after epithelial injury and as a suitable target for down-regulation as a disease-modifying strategy.New and noteworthyThis study identifies a distinct role for stress kinase MAPK13 in controlling the epithelial stem cell response to injury and the consequent development of tissue remodeling. The present model has direct implications for lung injury and subsequent disease triggered by respiratory viruses and other inhaled toxins, but the tissue distribution of MAPK13 implies related actions at other barrier sites. The findings also refine a hypothesis for therapeutic intervention based on proper scaling of MAPK13 function including down-regulation with selective kinase inhibitors.
Nitrate reductase activity is required inMedicago truncatula-Sinorhizobium melilotinitrogen-fixing symbiosis
Authors: Marc Bosseno , Alexandre Demba , Natasha Horta Araújo , Dominique Colinet , Marie Pacoud , Yassine El Fazaa , Marc Lepetit , Gilles Clément , Renaud Brouquisse , Alexandre Boscari 
Published: June 2024

AbstractNitrate reductase (NR) is a key enzyme in higher land plants, catalyzing the rate-limiting reduction of nitrate to nitrite in the nitrate assimilation pathway. Phylogenetic analysis of NR protein sequences indicates that duplication events responsible for the existence of two NR branches, corresponding to NR1 and NR2 genes, occurred after the divergence of the different orders within the Rosids clade. A third NR sequence branch, named NR3-type, emerged in the inverted repeat-lacking clade of the Fabales order. An intriguing feature of the NR3-type sequences is the absence of conserved phosphorylation sites in the two hinge regions, in contrast to all other NRs. To investigate the respective roles ofMtNR1,MtNR2andMtNR3inM. truncatula, three singleTnt1retrotransposon-taggednrmutants and onenr1/nr2double mutant were analyzed on plants growing either on nitrate, or during the nodulation process. Overall, the absence of phenotypes observed inM. truncatulasingle mutants suggests a significant functional redundancy between the different NRs inM. truncatula. The most striking outcome of this work is the almost complete impairment of nodulation capacity observed in thenr1/nr2double mutant, demonstrating that NR activity is required for the functioning of the N2-fixing symbiosis.
Isolation and characterisation of serine proteases and metalloproteases from the venom of African puff adders
Authors: Wilkinson Mark C. , Modahl Cassandra M. , Saviola Anthony , Albulescu Laura-Oana , Tianyi Frank-Leonel , Casewell Nicholas R. 
Published: June 2024

AbstractThe puff adder (Bitis arietans) is a highly venomous viperid snake responsible for many fatalities in Africa, yet despite this there have been few comprehensive analyses of its venom proteins, particularly of the proteases that play a key role in envenoming. This study set out to isolate and characterise the most abundant serine proteases and metalloproteases found in venoms of puff adders obtained from Nigeria, Tanzania and Kenya. All three contained both classes of protease, but there were clear regional differences in the types of protease and their activities. Prominent in all three venoms was an SVMP PII-a. This protease varied in degree of glycosylation between the three sources, and also in its activity. The protease isolated from Tanzanian venoms, which was non-glycosylated, proved to be highly potent, and very destructive towards laminin in particular. The SVMP PIII content of the three venoms was quite low, but in some Kenyan venoms a prominent 68 kDa SVMP PIII was found which has a novel non-covalent dimeric structure and was strongly gelatinolytic, an activity that was not observed in any of the other SVMPs identified here. The Nigerian venoms were rich in an interesting set of serine proteases (SVSPs), the main forms of which were isolated and characterised. Two distinct groups were identified: trypsin-like acidic SVSPs and chymotrypsin-like basic SVSPs, each with different activities. The acidic SVSP is responsible for the gelatinase activity observed in the Nigerian venom, which is a novel form of activity for SVSPs. This regional diversity in venom protease activities is discussed with reference to the implications it will have in the development of therapeutic interventions.
Translation and Validation of an Epilepsy Screening Instrument in Two Ghanaian Languages
Authors: Darkwa Emmanuel Kwame , Asiamah Sabina , Awini Elizabeth , Sottie Cynthia , Godi Anthony , Williams John E , Akpalu Albert , Cross J Helen , Sander Josemir W. , Sen Arjune , Newton Charles R. , Danso-Appiah Anthony , Adjei Patrick 
Published: June 2024

ABSTRACTIntroductionThe prevalence of epilepsy in sub-Saharan Africa varies considerably, and the exact estimate in Ghana is unknown, with few data available from peri-urban areas. More community-based studies are required to understand the tangible burden of epilepsy in these areas and the difficulties in healthcare access.ObjectiveTo validate a household survey epilepsy-screening instrument in Shai-Osudoku and Ningo-Prampram District of Greater Accra Region, Ghana.MethodsWe developed a 17-item epilepsy screening instrument by modifying validated English language questionnaires. We included questions that could identify convulsive and non-convulsive seizures. Language experts translated and back-translated the survey instrument into the two languages in this region: Asante Twi and Dangme. Cases were people with epilepsy attending healthcare facilities where these languages are used. Controls were unaffected relatives of cases or people attending the healthcare centres for other medical conditions. We matched cases and controls for geographical location and ethnicity. An affirmative response to one of the seventeen questions was deemed as a positive screen.ResultsOne hundred and Forty Dangme Twi speakers (70 cases and 70 controls) and 100 Twi speakers (50 cases and 50 controls) were recruited. The sensitivity and specificity for Dangme were: Stage 1;100% (95% CI: 88.6, 94.9) and 80% (95% CI: 68.7, 88.6) and Stage 2, 98.6% (95% CI: 92.3, 100.0) and 85.7% (95% CI: 75.3, 92.9). The Dangme version reliably identified epilepsy with positive predictive values of 83.3% (95% CI: 73.6, 90.6) and 87.3% (95% CI: 78.6, 90.6) at stages 1 and 2. The questionnaire excluded epilepsy with negative predictive values of 100% (95% CI: 93.6, 100.0) and 98.4% (95% CI: 91.2, 100.0). For the Twi version, the sensitivity and specificity were: 98% (95% CI: 89.4, 99.9) and 92% (95% CI: 80.8, 97.8) at Stage 1, and for Stage 2, 96% (95% CI: 86.3, 99.5) and 94% (95% CI 83.5, 98.7). The Twi questionnaire reliably specified epilepsy with positive predictive values of 92.5% (95% CI: 81.8%, 97.9) and 94.1% (95% CI: 83.8, 98.8) at stages 1 and 2. It excluded epilepsy with negative predictive values of 97.9% (95% CI: 88.7, 99.9) and 95.9% (95% CI: 86.0, 99.5) for the two-stagesConclusionsOur questionnaire is valid for the two tested languages and is usable for community-based epilepsy surveys in Ghana. The questionnaire can be adapted for other resource-poor settings, although there will need to be translation and iterative in-country testing to ensure its validity is maintained.
Human motion data expansion from arbitrary sparse sensors with shallow recurrent decoders
Authors: Ebers Megan R. , Pitts Mackenzie , Kutz J. Nathan , Steele Katherine M. 
Published: June 2024

AbstractAdvances in deep learning and sparse sensing have emerged as powerful tools for monitoring human motion in natural environments. We develop a deep learning architecture, constructed from a shallow recurrent decoder network, that expands human motion data by mapping a limited (sparse) number of sensors to a comprehensive (dense) configuration, thereby inferring the motion of unmonitored body segments. Even with a single sensor, we reconstruct the comprehensive set of time series measurements, which are important for tracking and informing movement-related health and performance outcomes. Notably, this mapping leverages sensor time histories to inform the transformation from sparse to dense sensor configurations. We apply this mapping architecture to a variety of datasets, including controlled movement tasks, gait pattern exploration, and free-moving environments. Additionally, this mapping can be subject-specific (based on an individual’s unique data for deployment at home and in the community) or group-based (where data from a large group are used to learn a general movement model and predict outcomes for unknown subjects). By expanding our datasets to unmeasured or unavailable quantities, this work can impact clinical trials, robotic/device control, and human performance by improving the accuracy and availability of digital biomarker estimates.
Reported transgenerational responses toPseudomonas aeruginosainC. elegansare not robust
Authors: Gainey D. Patrick , Shubin Andrey V. , Hunter Craig P. 
Published: June 2024

AbstractHere we report our attempt to replicate reports of transgenerational epigenetic inheritance inCaenorhabditis elegans. Published results from multiple laboratories show thatC. elegansadults and their F1 embryos exposed to the pathogenPseudomonas aeruginosashow pathogen aversion behavior and a pathogen exposure-dependent increase indaf-7/TGFβreporter gene expression. However, results from one group show persistence of the aversion behavior and elevateddaf-7expression in the F2, F3, and F4 generations. In contrast, we failed to consistently detect either the pathogen avoidance response or elevateddaf-7expression beyond the F1 generation. We did confirm that the dsRNA transport proteins SID-1 and SID-2 are required for the intergenerational (F1) inheritance of pathogen avoidance, but not for the F1 inheritance of elevateddaf-7expression. Furthermore, our reanalysis of RNA seq data provides additional evidence that this intergenerational inherited PA14 response may be mediated by small RNAs. The experimental methods are well-described, the source materials are readily available, including samples from the reporting laboratory, and we explored a variety of environmental conditions likely to account for lab-to-lab variability. None of these adjustments altered our results. We conclude that this example of transgenerational inheritance lacks robustness, confirm that the intergenerational avoidance response, but not the elevateddaf-7p::gfpexpression in F1 progeny, requiressid-1andsid-2, and identify candidate siRNAs and target genes that may mediate this intergenerational response.
The small non-coding RNAVaultrc5is dispensable to mouse development
Authors: Prajapat Mahendra , Sala Laura , Vidigal Joana A. 
Published: June 2024

ABSTRACTVault RNAs (vRNAs) are evolutionarily conserved small non-coding RNAs transcribed by RNA polymerase lll. Initially described as components of the vault particle, they have since also been described as noncanonical miRNA precursors and as riboregulators of autophagy. As central molecules in these processes, vRNAs have been attributed numerous biological roles including regulation of cell proliferation and survival, response to viral infections, drug resistance, and animal development. Yet, their impact to mammalian physiology remains largely unexplored. To study vault RNAsin vivo,we generated a mouse line with a conditionalVaultrc5loss of function allele. BecauseVaultrc5is the sole murine vRNA, this allele enables the characterization of the physiological requirements of this conserved class of small regulatory RNAs in mammals. Using this strain, we show that mice constitutively null forVaultrc5are viable and histologically normal but have a slight reduction in platelet counts pointing to a potential role for vRNAs in hematopoiesis. This work paves the way for furtherin vivocharacterizations of this abundant but mysterious RNA molecule. Specifically, it enables the study of the biological consequences of constitutive or lineage-specificVaultrc5deletion and of the physiological requirements for an intactVaultrc5during normal hematopoiesis or in response to cellular stresses such as oncogene expression, viral infection, or drug treatment.
CRISPRi-based screen of Autism Spectrum Disorder risk genes in microglia uncovers roles ofADNPin microglia endocytosis and synaptic pruning
Authors: Teter Olivia M , McQuade Amanda , Hagan Venus , Liang Weiwei , Dräger Nina M , Sattler Sydney M , Holmes Brandon B , Castillo Vincent Cele , Papakis Vasileios , Leng Kun , Boggess Steven , Nowakowski Tomasz J , Wells James , Kampmann Martin 
Published: June 2024

AbstractAutism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with complex biology. The identification of ASD risk genes from exome-wide association studies and de novo variation analyses has enabled mechanistic investigations into how ASD-risk genes alter development. Most functional genomics studies have focused on the role of these genes in neurons and neural progenitor cells. However, roles for ASD risk genes in other cell types are largely uncharacterized. There is evidence from postmortem tissue that microglia, the resident immune cells of the brain, appear activated in ASD. Here, we used CRISPRi-based functional genomics to systematically assess the impact of ASD risk gene knockdown on microglia activation and phagocytosis. We developed an iPSC-derived microglia-neuron coculture system and high-throughput flow cytometry readout for synaptic pruning to enable parallel CRISPRi-based screening of phagocytosis of beads, synaptosomes, and synaptic pruning. Our screen identifiedADNP, a high-confidence ASD risk genes, as a modifier of microglial synaptic pruning. We found that microglia with ADNP loss have altered endocytic trafficking, remodeled proteomes, and increased motility in coculture.
A machine learning framework for extracting information from biological pathway images in the literature
Authors: Kwon Mun Su , Lee Junkyu , Kim Hyun Uk 
Published: June 2024

AbstractThere have been significant advances in literature mining, allowing for the extraction of target information from the literature. However, biological literature often includes biological pathway images that are difficult to extract in an easily editable format. To address this challenge, this study aims to develop a machine learning framework called the “Extraction of Biological Pathway Information” (EBPI). The framework automates the search for relevant publications, extracts biological pathway information from images within the literature, including genes, enzymes, and metabolites, and generates the output in a tabular format. For this, this framework determines the direction of biochemical reactions, and detects and classifies texts within biological pathway images. Performance of EBPI was evaluated by comparing the extracted pathway information with manually curated pathway maps. EBPI will be useful for extracting biological pathway information from the literature in a high-throughput manner, and can be used for pathway studies, including metabolic engineering.