bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenology and social status of the endemic Sable Island Sweat Bee,Lasioglossum sablense
Authors: Richards Miriam H , Lucas Zoe , Proulx Alex , Corbin Lyllian A-J , Jacks Frederica , Kehler Dan 
Published: May 2023

AbstractThe Sable Island Sweat Bee (Lasioglossum (Dialictus) sablenseGibbs, 2010) is endemic to Sable Island, an isolated sandbar located about 160 km east of Nova Scotia.L. sablenseis classified as Threatened due to its restricted geographic distribution, so promoting its conservation requires detailed information about nesting phenology and behaviour. We combined measurements and dissections of adult females collected in 2016 and 2017 with behavioural observations of nests and foragers on the grounds of the Sable Island Station in 2019 and 2022, to compile the first description of flight phenology and social status. Like many members of its subgenus,L. sablenseexhibits a diphasic life history. Phase 1 begins when large adult females emerge from hibernation, begin burrow and brood cell construction, and forage to provision Brood 1, which comprises both daughters and sons. Most, but not all, nests initiated during Phase 1, reactivate during Phase 2, as adult Brood 1 daughters emerge from their nests and initiate foraging to provision Brood 2. This suggests a mix of univoltine (single generation) and bivoltine (two generation) reproductive strategies. Behavioural observations at nest entrances demonstrated that during Phase 2, reactivated nests sometimes contained multiple adult females, suggesting the potential for colonies to become social. Comparisons of body size and ovarian status of Phase 1 and 2 females collected from flowers, showed Phase 2 foragers were significantly smaller than Phase 1 foragers and had somewhat lower levels of ovarian development, as expected if Phase 2 females were workers from eusocial nests. However, five large females collected during Phase 2, which had high levels of wear, likely were Phase 1 foundresses that resumed foraging during Phase 2. Taken together, these observations suggest a mix of phenological and social strategies, including both univoltine and bivoltine life histories, and a mix of solitary and social behaviour among reactivated colonies in Phase 2.
Dynamic PRC1-CBX8 stabilizes a porous structure of chromatin condensates
Authors: Uckelmann Michael , Levina Vita , Taveneau Cyntia , Ng Xiao Han , Pandey Varun , Martinez Jasmine , Mendiratta Shweta , Houx Justin , Boudes Marion , Venugopal Hari , Trépout Sylvain , Zhang Qi , Flanigan Sarena , Li Minrui , Sierecki Emma , Gambin Yann , Das Partha Pratim , Bell Oliver , de Marco Alex , Davidovich Chen 
Published: May 2023

AbstractThe compaction of chromatin is a prevalent paradigm in gene repression. Chromatin compaction is commonly thought to repress transcription by restricting chromatin accessibility. However, the spatial organisation and dynamics of chromatin compacted by gene-repressing factors are unknown. Using cryo-electron tomography, we solved the three-dimensional structure of chromatin condensed by the Polycomb Repressive Complex 1 (PRC1) in a complex with CBX8. PRC1-condensed chromatin is porous and stabilised through multivalent dynamic interactions of PRC1 with chromatin. Mechanistically, positively charged residues on the internally disordered regions (IDRs) of CBX8 mask negative charges on the DNA to stabilize the condensed state of chromatin. Within condensates, PRC1 remains dynamic while maintaining a static chromatin structure. In differentiated mouse embryonic stem cells, CBX8-bound chromatin remains accessible. These findings challenge the idea of rigidly compacted polycomb domains and instead provides a mechanistic framework for dynamic and accessible PRC1-chromatin condensates.
The genomic landscape of transposable elements in yeast hybrids is shaped by structural variation and genotype-specific modulation of transposition rate
Authors: Hénault Mathieu , Marsit Souhir , Charron Guillaume , Landry Christian R. 
Published: May 2023

AbstractTransposable elements (TEs) are major contributors to structural genomic variation by creating interspersed duplications of themselves. In return, structural variants (SVs) can affect the genomic distribution of TE copies and shape their load. One long-standing hypothesis states that hybridization could trigger TE mobilization and thus increase TE load in hybrids. We previously tested this hypothesis by performing a large-scale evolution experiment by mutation accumulation (MA) on multiple hybrid genotypes within and between wild populations of the yeastsSaccharomyces paradoxusandSaccharomyces cerevisiae. Using aggregate measures of TE load with short-read sequencing, we found no evidence for TE load increase in hybrid MA lines. Here, we resolve the genomes of the hybrid MA lines with long-read phasing and assembly to precisely characterize the role of SVs in shaping the TE landscape. Highly contiguous phased assemblies of 127 MA lines revealed that SV types like polyploidy, aneuploidy and loss of heterozygosity have large impacts on the TE load. We characterized 18 de novo TE insertions, indicating that transposition only has a minor role in shaping the TE landscape in MA lines. Because the scarcity of TE mobilization in MA lines provided insufficient resolution to confidently dissect transposition rate variation in hybrids, we adapted an in vivo assay to measure transposition rates in variousS. paradoxushybrid backgrounds. We found that transposition rates are not increased by hybridization, but are modulated by many genotype-specific factors including initial TE load, TE sequence variants and mitochondrial DNA inheritance. Our results show the multiple scales at which TE load is shaped in hybrid genomes, being highly impacted by SV dynamics and finely modulated by genotype-specific variation in transposition rates.
World Health Organization Danger Signs to predict bacterial sepsis in newborns: A pragmatic prospective cohort study
Authors: Akinseye Omolabake , Popescu Constantin R. , Chiume-Kayuni Msandeni , Irvine Michael A. , Lufesi Norman , Mvalo Tisungane , Kissoon Niranjan , Wiens Matthew O. , Lavoie Pascal M. 
Published: May 2023

AbstractBackgroundThe World Health Organization (WHO) has developed danger signs (DS) to help front-line health workers triage interventions in children with severe illnesses. Our objective was to evaluate the extent to which DS predict bacterial sepsis in young infants presenting with acute illness.Methodology/Principal FindingsThis prospective study evaluated nine DS in infants younger than 3 months with suspected sepsis in a large regional hospital in Lilongwe, Malawi, between June 2018 and April 2020. The main outcomes were positive blood or cerebrospinal fluid (CSF) cultures and mortality. Blood (n=85/401) and CSF (n=2/204) cultures were positive in 21.2% and 1% of infants, respectively (N=401; gestational age mean ± SD: 37.1±3.3 weeks, birth weight 2865±785 grams). In-hospital deaths occurred in 9.7% (N=39/401) of infants (61.5% within 48h of admission). In univariate analyses, all DS were associated with mortality except for temperature instability and tachypnea, whereas “infant was unable to feed” was the only DS significantly associated with bacterial sepsis.After co-variable adjustments, number of DS predicted mortality (OR: 1.75; 95%CI: 1.43–2.16; p<0.001; AUC-ROC: 0.756) but not positive cultures (OR 1.08; 95%CI: 0.92–1.30; p=0.336). Whether potential bacterial contaminants were included or not did not change results meaningfully.Conclusion/SignificanceDS predicted fatal outcomes but not positive cultures in a large regional hospital setting. These data imply that the incidence of bacterial sepsis and attributable mortality are unlikely to be accurate based on clinical signs alone, in infants in LMIC settings.
Integration of leaf spectral reflectance variability facilitates identification of plant leaves at different taxonomic levels
Authors: Quinteros Casaverde Natalia L. , Serbin Shawn P. , Daly Douglas C. 
Published: May 2023

AbstractPlant identification is crucial to the conservation and management of natural areas. The shortwave spectral reflectance of leaves is a promising tool for rapidly identifying species at different taxonomic ranks. However, the spectral reflectance of leaves changes in response to biotic and abiotic conditions. This investigation asked how this variability affects the accuracy of methods used to predict plant taxonomies and what factors most influence the spectral signature of leaves. To answer these questions, we measured the reflectance of leaves of 62 woody species from the living collection at the NYBG twice in two pairwise samplings. We found that PLS-DA accuracy improved when we used a larger sample of natural variance in the classification model. Finally, to evaluate whether there was an influence of the species’ relatedness or the growing environment on structural and biochemical traits predicted from the leaf reflectance, we ran a phylogenetic signal analysis and a series of mixed effects model analyses that showed no phylogenetic but an environmental influence. We found that the increase in temperature and relative humidity variability explained the increment of predicted carotene and the decrease of Nitrogen content for the first pairwise analysis. For the second pairwise analysis, we found that the reduction of relative humidity variability explained leaf water and Nitrogen content decrease, and relative humidity decrease combined with day length decrease explained a decline in LMA.
A deep catalog of protein-coding variation in 985,830 individuals
Authors: Sun Kathie Y. , Bai Xiaodong , Chen Siying , Bao Suying , Kapoor Manav , Zhang Chuanyi , Backman Joshua , Joseph Tyler , Maxwell Evan , Mitra George , Gorovits Alexander , Mansfield Adam , Boutkov Boris , Gokhale Sujit , Habegger Lukas , Marcketta Anthony , Locke Adam , Kessler Michael D. , Sharma Deepika , Staples Jeffrey , Bovijn Jonas , Gelfman Sahar , Gioia Alessandro Di , Rajagopal Veera , Lopez Alexander , Varela Jennifer Rico , Alegre Jesus , Berumen Jaime , Tapia-Conyer Roberto , Kuri-Morales Pablo , Torres Jason , Emberson Jonathan , Collins Rory ,   Regeneron Genetics Center,   RGC-ME Cohort Partners, Cantor Michael , Thornton Timothy , Kang Hyun Min , Overton John , Shuldiner Alan R. , Cremona M. Laura , Nafde Mona , Baras Aris , Abecasis Goncalo , Marchini Jonathan , Reid Jeffrey G. , Salerno William , Balasubramanian Suganthi 
Published: May 2023

ABSTRACTCoding variants that have significant impact on function can provide insights into the biology of a gene but are typically rare in the population. Identifying and ascertaining the frequency of such rare variants requires very large sample sizes. Here, we present the largest catalog of human protein-coding variation to date, derived from exome sequencing of 985,830 individuals of diverse ancestry to serve as a rich resource for studying rare coding variants. Individuals of African, Admixed American, East Asian, Middle Eastern, and South Asian ancestry account for 20% of this Exome dataset. Our catalog of variants includes approximately 10.5 million missense (54% novel) and 1.1 million predicted loss-of-function (pLOF) variants (65% novel, 53% observed only once). We identified individuals with rare homozygous pLOF variants in 4,874 genes, and for 1,838 of these this work is the first to document at least one pLOF homozygote. Additional insights from the RGC-ME dataset include 1) improved estimates of selection against heterozygous loss-of-function and identification of 3,459 genes intolerant to loss-of-function, 83 of which were previously assessed as tolerant to loss-of-function and 1,241 that lack disease annotations; 2) identification of regions depleted of missense variation in 457 genes that are tolerant to loss-of-function; 3) functional interpretation for 10,708 variants of unknown or conflicting significance reported in ClinVar as cryptic splice sites using splicing score thresholds based on empirical variant deleteriousness scores derived from RGC-ME; and 4) an observation that approximately 3% of sequenced individuals carry a clinically actionable genetic variant in the ACMG SF 3.1 list of genes. We make this important resource of coding variation available to the public through a variant allele frequency browser. We anticipate that this report and the RGC-ME dataset will serve as a valuable reference for understanding rare coding variation and help advance precision medicine efforts.
NGBO: Introducing -omics metadata to biobanking ontology
Authors: Alghamdi Dalia , Dooley Damion M. , Samman Mannar , Hsiao William W.L. 
Published: May 2023

ABSTRACTBackgroundWith improvements in high throughput sequencing technologies and the constant generation of large biomedical datasets, biobanks increasingly take on the role of managing and delivering not just specimens but also data. However, re-using data from different biobanks is challenged by incompatible data representations. Contextual data describing biobank digital resources often contain unstructured textual information incompatible with computational processes such as automated data discovery and integration. Therefore, a consistent and comprehensive contextual data framework is needed to increase discovery, reusability, and integrability across data sources.MethodsBased on available genomics standards (e.g., Minimum information about a microarray experiment (MIAME)), the College of American Pathologists (CAP) laboratory accreditation requirements, and the Open Biological and Biomedical Ontologies Foundry principles, we developed the Next Generation Biobanking Ontology (NGBO). In addition, we created new terms and re-used concepts from the Ontology for Biomedical Investigations (OBI) and the Ontology for Biobanking (OBIB) to build NGBO.ResultsThe Next Generation Biobanking Ontologyhttps://www.ebi.ac.uk/ols4/ontologies/ngbois an open application ontology representing omics contextual data, licensed under the Apache License 2.0. The ontology focuses on capturing information about three main activities: wet bench analysis used to generate omics data, bioinformatics analysis used to process and interpret data, and data management. In this paper, we demonstrated the use of the NGBO to add semantic statements to real-life use cases and query data previously stored in unstructured textual format.
Molecular signatures associated with successful implantation of the human blastocyst
Authors: Chousal Jennifer N. , Srinivasan Srimeenakshi , Lee Katherine , To Cuong , Cho Kyucheol , Zhang Wei , Yeo Ana Lisa , Garzo V. Gabriel , Parast Mana M. , Laurent Louise C. , Cook-Andersen Heidi 
Published: May 2023

AbstractEmbryo implantation in humans is remarkably inefficient for reasons that remain largely unexplained, and high rates of implantation failure remain one of the greatest obstacles in treating infertility. The volume of gene expression data available from human embryos has rapidly accumulated in recent years. However, prioritization of these data to identify the subset of genes that determine successful implantation remains a challenge, in part, because comprehensive analyses cannot be performed on the same embryos that are transferred. Here, we leverage clinical morphologic grading—known for decades to correlate with implantation potential—and transcriptome analyses of matched embryonic and abembryonic samples to identify genes and cell-cell interactions enriched and depleted in human blastocysts of good and poor morphology, genome-wide. Unexpectedly, we discovered that the greatest molecular difference was in the state of the extraembryonic primitive endoderm (PrE), with relative deficiencies in PrE development in embryos of poor morphology at the time of embryo transfer. Together, our results support a model in which implantation success is most strongly reflected by factors and signals from the embryonic compartment and suggest that deficiencies in PrE development, in particular, are common among embryos with reduced implantation potential. Our study provides a valuable resource for those investigating the markers and mechanisms of human embryo implantation.
The Development of Resistance to an Inhibitor of a Cellular Protein Reveals a critical interaction between the enterovirus protein 2C and a small GTPase Arf1
Authors: Viktorova Ekaterina G. , Gabaglio Samuel , Moghimi Seyedehmahsa , Zimina Anna , Wynn Bridge G. , Sztul Elizabeth , Belov George A. 
Published: May 2023

AbstractThe cellular protein GBF1, an activator of Arf GTPases (ArfGEF: Arf guanine nucleotide exchange factor), is recruited to the replication organelles of enteroviruses through interaction with the viral protein 3A, and its ArfGEF activity is required for viral replication. Here, we investigated the development of resistance of poliovirus, a prototype enterovirus, to increasing concentrations of brefeldin A (BFA), an inhibitor of GBF1. High level of resistance required a gradual accumulation of multiple mutations in the viral protein 2C. The 2C mutations conferred BFA resistance even in the context of a 3A mutant previously shown to be defective in the recruitment of GBF1 to replication organelles, and in cells depleted of GBF1, suggesting a GBF1-independent replication mechanism. Still, activated Arfs accumulated on the replication organelles of this mutant even in the presence of BFA, its replication was inhibited by a pan-ArfGEF inhibitor LM11, and the BFA-resistant phenotype was compromised in Arf1-knockout cells. Importantly, the mutations strongly increased the interaction of 2C with the activated form of Arf1. Analysis of other enteroviruses revealed a particularly strong interaction of 2C of human rhinovirus 1A with activated Arf1. Accordingly, the replication of this virus was significantly less sensitive to BFA than that of poliovirus. Thus, our data demonstrate that enterovirus 2Cs may behave like Arf1 effector proteins and that GBF1 but not Arf activation can be dispensable for enterovirus replication. These findings have important implications for the development of host-targeted anti-viral therapeutics.
Dissecting the impact of somatic hypermutation on SARS-CoV-2 neutralization and viral escape
Authors: Korenkov Michael , Zehner Matthias , Cohen-Dvashi Hadas , Borenstein-Katz Aliza , Kottege Lisa , Janicki Hanna , Vanshylla Kanika , Weber Timm , Gruell Henning , Koch Manuel , Diskin Ron , Kreer Christoph , Klein Florian 
Published: May 2023

SUMMARYSomatic hypermutation (SHM) drives affinity maturation and continues over months in SARS-CoV-2 neutralizing antibodies. Yet, several potent SARS-CoV-2 antibodies carry no or only few mutations, leaving the question of how ongoing SHM affects neutralization. Here, we reverted variable region mutations of 92 antibodies and tested their impact on SARS-CoV-2 binding and neutralization. Reverting higher numbers of mutations correlated with decreasing antibody functionality. However, some antibodies, including the public clonotype VH1-58, remained unaffected for Wu01 activity. Moreover, while mutations were dispensable for Wu01-induced VH1-58 antibodies to neutralize Alpha, Beta, and Delta variants, they were critical to neutralize Omicron BA.1/BA.2. Notably, we exploited this knowledge to convert the clinical antibody tixagevimab into a BA.1/BA.2-neutralizer. These findings substantially broaden our understanding of SHM as a mechanism that not only improves antibody responses during affinity maturation, but also counteracts antigenic imprinting through antibody diversification and thus increases the chances of neutralizing viral escape variants.
Phase-dependent stimulation response is shaped by the brain’s transient collective dynamics
Authors: Benitez Stulz Sophie , Gutkin Boris , Gilson Matthieu , Battaglia Demian 
Published: May 2023

AbstractExogenous stimulation is a promising tool for investigating and altering cognitive processes in the brain, with potential clinical applications. Following experimental observations, we hypothesise that the effect of stimulation crucially depends on the endogenous dynamics of the brain. Our study explores how local and global dynamical properties, like the stimulation phase of regional oscillatory activity and the transient network states, modulate the effect of single pulse stimulation in a large-scale network. Our findings demonstrate that the effect of stimulation strongly depends on the interplay between stimulated phase, transient network state, and brain region. Importantly, we show that stimulation is not only state-dependent but can also induce global state switching. Lastly, predicting the effect of stimulation by using machine learning shows that state-aware measures can increase the performance by up to 40%. Our results suggest that a fine characterisation of the complex brain dynamics in experimental setups is essential for improving the reliability of exogenous stimulation.
Deficits in neural encoding of speech in preterm infants
Authors: Novitskiy Nikolay , Chan Peggy H. Y. , Chan Mavis , Lai Chin Man , Leung Tak Yeung , Leung Ting Fan , Bornstein Marc H. , Lam Hugh S. , Wong Patrick C. M. 
Published: May 2023

AbstractPreterm children show developmental cognitive and language deficits that can be subtle and sometimes undetectable until later in life. Studies of brain development in children who are born preterm have largely focused on vascular and gross anatomical characteristics rather than pathophysiological processes that may contribute to these developmental deficits. Neural encoding of speech as reflected in EEG recordings is predictive of future language development and could provide insights into those pathophysiological processes. We recorded EEG from 45 preterm (≤ 34 weeks of gestation) and 45 full-term (≥ 38 weeks) Chinese-learning infants 0 to 12 months of (corrected) age during natural sleep. Each child listened to three speech stimuli that differed in lexically meaningful pitch (2 native and 1 non-native speech categories). EEG measures associated with synchronization and gross power of the frequency following response (FFR) were examined. ANCOVAs revealed no main effect of stimulus nativeness but main effects of age, consistent with earlier studies. A main effect of prematurity also emerged, with synchronization measures showing stronger group differences than power. By detailing differences in FFR measures related to synchronization and power, this study brings us closer to identifying the pathophysiological pathway to often subtle language problems experienced by preterm children.