bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-Cambrian origin ofenvelope-carrying endogenous retroviruses in metazoans
Authors: Chary Shashank , Hayashi Rippei 
Published: October 2023

AbstractRetrotransposons or endogenous retroviruses (ERVs) essentially carry open reading frames ofgagandpol, which are utilized to selfishly replicate themselves in the host’s germline genome. One rare example of ERVs that additionally carryenvelopegenes, are Ty3/gypsyerrantiviruses in Drosophila. Though they are structurally analogous to vertebrate retroviruses, their evolutionary relationship as well as the origin ofenvelopegenes remain elusive. We systematically searched for intactenvelope-containing ERVs that are homologous to Ty3/gypsyand vertebrate retroviruses in metazoan genomes and found that they are widespread across taxa including ancient animals such as Cnidarians, Ctenophores and Tunicates. Most elements are multiplied in their respective genomes, implying recent germline expansion.Envelopegenes are classified into those that resemble glycoprotein F from paramyxoviruses (F-type), glycoprotein B from herpesviruses (HSV/gB-type), and GP2 glycoprotein from retroviruses and Ebolavirus (GP2-type). Both F-type and HSV/gB-type ERVs are ubiquitously found in invertebrate genomes while vertebrate genomes carry F-type and GP2-type ERVs. Interestingly, vertebrate ERVs share a distinct and structurally conserved domain of POL with Ty3/gypsyelements from insects and ancient animals, suggesting that they share common origins. Furthermore, phylogenetic and structural analyses revealed thatenvelopegenes have largely diverged withpolgenes as well as with the host organisms throughout their evolutionary history and recombined infrequently, suggesting that theenvelopeacquisition to ERVs is ancient and likely dates to before the split of bilaterian and non-bilaterian animals in Pre-Cambrian era.
VisualR: a novel and scalable solution for assessing visual function using virtual reality
Authors: Sozzi Federica , Groß Henning , Ljubisic Bratislav , Adams Jascha , Gyacsok Andras , Graziano Giuseppe , Weiß Steffen , Pires Nuno D. 
Published: October 2023

AbstractBackgroundDiagnosis and treatment of progressive eye diseases require effective monitoring of visual structure and function. However, current methods for measuring visual function are limited in accuracy, reliability, and usability. We propose a novel approach that leverages virtual reality (VR) technology to overcome these challenges, enabling more comprehensive measurements of visual function endpoints.ResultsWe developed VisualR, a low-cost VR-based application that consists of a smartphone app and a simple VR headset. The virtual environment allows precise control of visual stimuli, full control over the field of view, separating visual input to the left and right eyes, controlling visual angles and blocking background visual noise. We developed novel tests for metamorphopsia, contrast sensitivity and reading speed that can be performed by following simple instructions and providing verbal responses to visual cues, without the need for expert supervision. The smartphone app does not require an internet connection, handles all data processing and image display, and all data is stored locally and owned by the user.ConclusionVisualR demonstrates the feasibility of building a visual function test device using consumer-grade hardware. Eventually, this technology could be used to measure visual function endpoints during clinical development of new treatments and to support disease diagnosis and monitoring. We open-sourced the application code and provide guidelines for creating reliable and user-friendly VR-based tests. We believe VR can open a new paradigm in visual function testing, and invite the wider community to build upon our work.
Associations Between Polygenic Scores for Cognitive and Non-cognitive Factors of Educational Attainment and Measures of Behavior, Psychopathology, and Neuroimaging in the Adolescent Brain Cognitive Development Study
Authors: Gorelik Aaron J. , Paul Sarah E. , Miller Alex P. , Baranger David A.A. , Lin Shuyu , Zhang Wei , Elsayed Nourhan M. , Modi Hailey , Addala Pooja , Bijsterbosch Janine , Barch Deanna M. , Karcher Nicole R. , Hatoum Alexander S. , Agrawal Arpana , Bogdan Ryan , Johnson Emma C. 
Published: October 2023

AbstractBackgroundBoth cognitive and non-cognitive (e.g., traits like curiosity) factors are critical for social and emotional functioning and independently predict educational attainment. These factors are heritable and genetically correlated with a range of health-relevant traits and behaviors in adulthood (e.g., risk-taking, psychopathology). However, whether these associations are present during adolescence, and to what extent these relationships diverge, could have implications for adolescent health and well-being.MethodsUsing data from 5,517 youth of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSMStudy, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and outcomes related to cognition, socioeconomic status, risk tolerance and decision-making, substance initiation, psychopathology, and brain structure.ResultsCognitive and non-cognitive PGSs were both positively associated with cognitive performance and family income, and negatively associated with ADHD and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk-taking, delayed discounting, and anorexia, as well as lower likelihood of nicotine initiation. The cognitive PGS was further associated with cognition scores and anorexia inwithin-siblinganalyses, suggesting these results do not solely reflect the effects of assortative mating or passive gene-environment correlations. The cognitive PGS showed significantly stronger associations with cortical volumes than the non-cognitive PGS and was associated with right hemisphere caudal anterior cingulate and pars-orbitalis inwithin-siblinganalyses, while the non-cognitive PGS showed stronger associations with white matter fractional anisotropy and a significantwithin-siblingassociation for right superior corticostriate-frontal cortex.ConclusionsOur findings suggest that PGSs for cognitive and non-cognitive factors show similar associations with cognition and socioeconomic status as well as other psychosocial outcomes, but distinct associations with regional neural phenotypes in this adolescent sample.
Outcomes of Percutaneous Coronary Intervention for Protected versus Unprotected Left Main Coronary Artery Disease: Insights from the VA CART Program
Authors: Gonzalez Pedro Engel , Hebbe Annika , Hussain Yasin , Khera Rohan , Banerjee Subhash , Plomondon Mary E , Waldo Stephen W. , Pfau Steven E. , Curtis Jeptha P. , Shah Samit M. 
Published: October 2023

AbstractBackgroundPractice patterns and outcomes of protected left main (PLM) and unprotected left main (ULM) percutaneous coronary intervention (PCI), as well as the differences between these types of PCI, are not well defined in real-world clinical practice.MethodsData collected from all Veteran Affairs (VA) catheterization laboratories participating in the Clinical Assessment Reporting and Tracking Program between 2009 and 2019. The analysis included 4,351 patients undergoing left main PCI, of which 1,306 pairs of PLM and ULM PCI were included in a propensity matched cohort. Patients and procedural characteristics were compared between PLM and ULM PCI. Temporal trends were also assessed. Peri-procedural and one-year major adverse cardiovascular events (MACE) were compared using cumulative incidence plots. The primary outcome was MACE outcomes at 1-year, which was defined as a composite of all-cause mortality, rehospitalization for myocardial infarction (MI), rehospitalization for stroke or urgent revascularization.ResultsULM PCI patients in comparison to PLM PCI were older (71.5 vs 69.2; P < 0.001), more clinically complex and more likely to present with ACS. In the propensity matched cohort, radial access was used more often for ULM PCI (21% [273] vs. 14% [185], P < 0.001), and ULM PCI was more likely to involve the LM bifurcation (22% vs 14%; P = 0.003) and require mechanical circulatory support (10% [134] vs 1% [17]; P <0.001). One-year MACE occurred more frequently with ULM PCI compared to PLM PCI (22% [289] vs. 16% [215]; P = < 0.001) and all-cause mortality was also higher (16% [213] vs. 10% [125]; P = < 0.001). In the matched cohort there was a low incidence of rehospitalization for MI (4% [48] ULM vs. 4% [48] PLM; P = 1.000) or revascularization (7% [94] ULM vs. 6% [84] PLM; P = 0.485).ConclusionsVeterans undergoing PLM PCI had better one-year outcomes than those undergoing ULM PCI, but in both groups there was a high rate of mortality and MACE at one-year despite a relatively low rate of MI or revascularization.
FAK family proteins regulatein vivobreast cancer metastasisviadistinct mechanisms
Authors: Genna Alessandro , Alter Joel , Poletti Martina , Meirson Tomer , Sneh Tal , Gendler Michal , Saleev Natalia , Karagiannis George S. , Wang Yarong , Cox Dianne , Entenberg David , Oktay Maja H. , Korcsmaros Tamas , Condeelis John S. , Gil-Henn Hava 
Published: October 2023

ABSTRACTBreast cancer is the most commonly diagnosed malignancy and the major leading cause of tumor-related deaths in women. It is estimated that the majority of breast tumor-related deaths are a consequence of metastasis, to which no cure exists at present. The FAK family proteins Proline-rich tyrosine kinase (PYK2) and focal adhesion kinase (FAK) are highly expressed in breast cancer, but the exact cellular and signaling mechanisms by which they regulatein vivotumor cell invasiveness and consequent metastatic dissemination are mostly unknown. Using a PYK2 and FAK knockdown xenograft model we show here, for the first time, that ablation of either PYK2 or FAK decreases primary tumor size and significantly reduces Tumor MicroEnvironment of Metastasis (TMEM) doorway activation, leading to decreased intravasation and reduced spontaneous lung metastasis. Intravital imaging analysis further demonstrates that PYK2, but not FAK, regulates a motility phenotype switch between focal adhesion-mediated fast motility and invadopodia-dependent, ECM-degradation associated slow motility within the primary tumor. Furthermore, we validate ourin vivoand intravital imaging results with integrated transcriptomic and proteomic data analysis from xenograft knockdown tumors and reveal new and distinct pathways by which these two homologous kinases regulate breast tumor cell invasiveness and consequent metastatic dissemination. Our findings identify PYK2 and FAK as novel mediators of mammary tumor progression and metastasis and as candidate therapeutic targets for breast cancer metastasis.
TheMarchantiapangenome reveals ancient mechanisms of plant adaptation to the environment
Authors: Beaulieu Chloé , Libourel Cyril , Mbadinga Zamar Duchesse Lacourt , Mahboubi Karima El , Hoey David J. , Keller Jean , Girou Camille , Clemente Helene San , Diop Issa , Amblard Emilie , Théron Anthony , Cauet Stéphane , Rodde Nathalie , Zachgo Sabine , Halpape Wiebke , Meierhenrich Anja , Laker Bianca , Brautigam Andrea , Greiff George RL ,   The SLCU Outreach Consortium, Szovenyi Peter , Cheng Shifeng , Tanizawa Yasuhiro , Leebens-Mack James H. , Schmutz Jeremy , Webber Jenel , Grimwood Jane , Jacquet Christophe , Dunand Christophe , Nelson Jessica M. , Roux Fabrice , Philippe Hervé , Schornack Sebastian , Bonhomme Maxime , Delaux Pierre-Marc 
Published: October 2023

AbstractPlant adaptation to a terrestrial life 450 million years ago played a major role in the evolution of life on Earth. This shift from an aquatic environment has been mostly studied by focusing on flowering plants. Here, we gathered a collection of 133 accessions of the non-vascular plantsMarchantia polymorphaand studied its intraspecific diversity using selection signature analyses, genome-environment association study and a gene-centered pangenome. We identified adaptive features shared with flowering plants, such as peroxidases or nucleotide-binding and leucine-rich repeat (NLR), which likely played a role in the adaptation of the first land plants to the terrestrial habitat. TheM. polymorphapangenome also harbored lineage-specific accessory genes absent from seed plants. We conclude that different land plants lineages still share many elements from the genetic toolkit evolved by their most recent common ancestor to adapt to the terrestrial habitat, refined by lineage specific polymorphisms and gene family evolutions.
Hybridde novoand haplotype resolved genome assembly of Vechur cattle - elucidating genetic variation
Authors: Muthusamy Poorvishaa V. , Mani Rajesh Vakayil , Kumari Shivani , Kaur Manpreet , Bhaskar Balu , Pillai Rajeev Raghavan , Kumar Thankappan Sajeev , Anilkumar Thapasimuthu Vijayamma , Singh N. Sadananda 
Published: October 2023

AbstractCattle contribute to the nutritional needs and economy of a place. Performance and fitness depends on the response and adaptation to local climatic conditions. Genomic and genetic studies are important for advancing cattle breeding and availability of relevant reference genomes are essential. In the present study, the genome of a Vechur calf was sequenced on both short-read illumina and long-read nanopore platforms. Hybridde novoassembly approach was deployed to obtain an average contigs length of 1.97 Mbp and N50 of 4.94 Mbp. Using a short-read genome sequence of the corresponding sire and dam, a haplotype-resolved genome was also assembled. In comparison to the taurine reference genome, we found 28982 autosomal structural variants, 16926990 SNVs with 883544 SNVs homozygous in the trio samples suggesting high prevalence of these SNPs in the population. Many of these SNPs have been reported to be associated with various QTLs including growth, milk yield and milk fat content which are crucial determinants of cattle production. Further, population genotype data analysis indicated that the present sample belongs to an Indian cattle breed forming a unique cluster ofBos indicus. Subsequent FSTanalysis revealed differentiation of Vechur cattle genome at multiple loci, especially those regions related to whole body growth and cell division especially IGF1, HMGA2, RRM2 and CD68 loci suggesting a possible role of these genes in its small stature and better disease resistance capabilities in comparison with the local crossbreeds. This provides an opportunity to select and engineer cattle breeds optimized for local conditions.
4D Crystallography Captures Transient IF1-Ribosome Dynamics in Translation Initiation
Authors: Yapici Ilkin , Dao E. Han , Yokoi Shun , Destan Ebru , Ayan Esra , Shafei Alaleh , Ertem Fatma Betul , Kulakman Cahine , Yilmaz Merve , Tosun Bilge , Ciftci Halilibrahim , Kepceoglu Abdullah , Johnson Jerome , Guven Omur , Ergul Ali , Hayes Brandon , Rao Yashas , Kupitz Christopher , Poitevin Frederic P. , Liang Mengling , Hunter Mark S. , Milon Pohl , Mitsutake Ayori , Sierra Raymond G. , Wakatsuki Soichi , DeMirci Hasan 
Published: October 2023

AbstractInitiation factor 1 (IF1) is one of multiple key ligands involved in the initiation of mRNA translation, a highly dynamic and carefully-orchestrated process. However, details surrounding IF1 transient interactions with the small 30S ribosomal subunit remain incompletely understood despite characterization of unbound and fully-bound 30S states. Improvements in X-ray light sources and crystallographic techniques are now enabling time-resolved structural studies at near-physiological temperature and near-atomic resolution and thus the structural investigation of such dynamic processes. Here, we employed time-resolved serial femtosecond X-ray crystallography (TR-SFX) to probe the binding of IF1 to the small 30S ribosomal subunit in real time. Our time-resolved structural data demonstrates transient cryptic short-, mid-, and long-range allostery among different regions of the small 30 ribosomal subunit during IF1 binding, revealing small- and large-scale protein-target interactions and dynamics within intermediate macromolecular states at unprecedented temporal and spatial resolution. These data represent one of the first such 4D crystallographic studies assessing protein-protein and protein-RNA interactions and could serve as the basis for subsequent studies of the ribosome and of the multitudinous dynamic processes which underpin biology, and therefore, of life.
Determining the defining lengths between mature microRNAs/small interfering RNAs and tinyRNAs
Authors: Sim GeunYoung , Kehling Audrey C. , Park Mi Seul , Divoky Cameron , Zhang Huaqun , Malhotra Nipun , Secor Jackson , Nakanishi Kotaro 
Published: October 2023

ABSTRACTMicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are loaded into Argonaute (AGO) proteins, forming RNA-induced silencing complexes (RISCs). The assembly process establishes the seed, central, 3′ supplementary, and tail regions across the loaded guide, enabling the RISC to recognize and cleave target RNAs. This guide segmentation is caused by anchoring the 3′ end at the AGO PAZ domain, but the minimum guide length required for the conformation remains to be studied because there was no method by which to do so. Using a 3′→5′ exonuclease ISG20, we determined the lengths of AGO-associated miR-20a and let-7a with 3′ ends that no longer reach the PAZ domain. Unexpectedly, miR-20a and let-7a needed different lengths, 19 and 20 nt, respectively, to maintain their RISC conformation. This difference can be explained by the low affinity of the PAZ domain for the adenosine at g19 of let-7a, suggesting that the tail-region sequence slightly alters the minimum guide length. We also present that 17-nt guides are sufficiently short enough to function as tinyRNAs (tyRNAs) whose 3’ ends are not anchored at the PAZ domain. Since tyRNAs do not have the prerequisite anchoring for the standardized guide segmentation, they would recognize targets differently from miRNAs and siRNAs.
Staphylococcus aureusPersistence in Osteocytes: Weathering the Storm of Antibiotics and Autophagy/Xenophagy
Authors: Gunn Nicholas J. , Zelmer Anja R. , Kidd Stephen P. , Solomon Lucian B. , Yang Dongqing , Roscioli Eugene , Atkins Gerald J. 
Published: October 2023

ABSTRACTBackgroundStaphylococcus aureusis a major causative pathogen of osteomyelitis. The intracellular infection of osteocytes and related bone cells can persist despite application of gold-standard clinical interventions. The mechanisms by which intracellularS. aureuspersists during antibiotic therapy are unknown. In this study, we applyS. aureusto anin vitromodel of differentiated osteocytes to investigate whether antibiotic-mediated dysregulation of autophagy contributes to this phenomenon.MethodsHuman osteocyte-like cells were exposed to combinations of rifampicin, vancomycin and modulators of autophagy, in the presence or absence ofS. aureus. Intracellular bacterial growth characteristics were assessed through CFU analysis, viable bacterial DNA abundance and the rate of escape into antibiotic-free medium, in parallel with measures of host cell autophagic flux.ResultsRifampicin, alone or in combination with vancomycin, caused a rapid decrease in the culturability of the intracellular bacterial community, concomitant with stable or increased absolute bacterial DNA levels. Both antibiotics significantly inhibited autophagic flux. However, while the modulation of autophagic flux affected bacterial culturability, this modulation did not affect viable bacterial DNA levels.ConclusionsAutophagy was shown to be a factor in the host-pathogen relationship in this model, as its modulation affected the growth state of intracellularS. aureuswith respect to both their culturability and propensity to escape the intracellular niche. Whilst rifampicin and vancomycin treatments moderately suppressed autophagic flux acutely, this did not explain the paradoxical response of antibiotic treatment in decreasingS. aureusculturability while failing to clear bacterial DNA and hence intracellular bacterial load. Thus, whilst rifampicin and vancomycin exhibited off-target effects that modulated autophagy in osteocyte-like cells, this could not explain the persistent infection observed forS. aureus.
Validation of body surface colonic mapping against high resolution colonic manometry: a novel non-invasive tool for evaluation of colonic motility
Authors: Seo Sean HB , Wells Cameron I , Dickson Tully , Rowbotham David , Gharibans Armen , Calder Stefan , Bissett Ian , O’Grady Greg , Erickson Jonathan C 
Published: October 2023

ABSTRACTAbnormal cyclic motor pattern (CMP) activity is implicated in colonic dysfunction, but the only tool to evaluate CMP activity, high-resolution colonic manometry (HRCM), remains expensive and not widely accessible. This study aimed to validate body surface colonic mapping (BSCM) through direct correlation with HRCM. Synchronous meal-test recordings were performed in asymptomatic participants with intact colons. A signal processing method for BSCM was developed to detect CMPs. Quantitative temporal analysis was performed comparing the meal responses and motility indices (MI). Spatial heat maps were also compared. Post-study questionnaire evaluated participants’ preference and comfort/distress experienced from either test. 11 participants were recruited and 7 had successful synchronous recordings (5 females/2 males; median age: 50 years [range: 38-63]). The best-correlating MI temporal analyses achieved a high degree of agreement (median Pearson correlation coefficient (Rp) value: 0.69; range: 0.47 - 0.77). HRCM and BSCM meal response start and end times (Rp= 0.998 and 0.83; bothp <0.05) and durations (Rp= 0.85;p= 0.03) were similar. Heat maps demonstrated good spatial agreement. BSCM is the first non-invasive method to be validated by demonstrating a direct spatio-temporal correlation to manometry in evaluating colonic motility.
Co-transcriptional capping using an RNA capping enzyme-T7 RNA polymerase fusion protein
Authors: Chan S. Hong , Tirole Louise , Kneller Daniel , Kelley Theresa M. , Dai Nan , Robb G. Brett 
Published: October 2023

AbstractmRNA vaccines and therapeutics are highly effective and can be developed and manufactured with a relatively short lead time. Here we report an all-enzyme platform to generate capped synthetic RNA in a one-step process based on an RNA capping enzyme-T7 RNA polymerase fusion protein. Under standard in vitro transcription reaction conditions, the fusion protein, in conjunction with an RNA cap 2′-O-methyltransferase, can generate synthetic mRNA with up to 95% of Cap-1 incorporation, greatly simplifying mRNA manufacturing workflows.