bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gaze onsets during naturalistic infant-caregiver interaction associate with ‘sender’ but not ‘receiver’ neural responses, and do not lead to changes in inter-brain synchrony
Authors: Marriott Haresign I. , Phillips E.A.M , Whitehorn M. , Lamagna F. , Eliano M. , Goupil L. , Jones E.J.H. , Wass S.V. 
Published: May 2022

AbstractTemporal coordination during infant-caregiver social interaction is thought to be crucial for supporting early language acquisition and cognitive development. Despite a growing prevalence of theories suggesting that increased inter-brain synchrony associates with many key aspects of social interactions such as mutual gaze, little is known about how this arises during development. Here, we investigated the role of mutual gazeonsetsas a potential driver of inter-brain synchrony. We extracted dual EEG activity around naturally occurring gaze onsets during infant-caregiver social interactions in N=55 dyads (mean age 12 months). We differentiated between two types of gaze onset, depending on each partners’ role. ‘Sender’ gaze onsets were defined at a time when either the adult or the infant made a gaze shift towards their partner at a time when their partner was either already looking at them (mutual) or not looking at them (non-mutual). ‘Receiver’ gaze onsets were defined at a time when their partner made a gaze shift towards them at a time when either the adult or the infant was already looking at their partner (mutual) or not (non-mutual). Contrary to our hypothesis we found that, during a naturalistic interaction, both mutual and non-mutual gaze onsets were associated with changes in the sender, but not the receiver’s brain activity and were not associated with increases in inter-brain synchrony above baseline. Further, we found that mutual, compared to non-mutual gaze onsets were not associated with increased inter brain synchrony. Overall, our results suggest that the effects of mutual gaze are strongest at the intra-brain level, in the ‘sender’ but not the ‘receiver’ of the mutual gaze.
Nanoneedles for targeted siRNA silencing of p16 in the Human Corneal Endothelium
Authors: Maurizi Eleonora , Martella Davide Alessandro , Schiroli Davide , Merra Alessia , Mustfa Salman Ahmad , Pellegrini Graziella , Macaluso Claudio , Chiappini Ciro 
Published: May 2022

AbstractNanoneedles can target nucleic acid transfection to primary cells at tissue interfaces with high efficiency and minimal perturbation. The corneal endothelium is an ideal target for nanoneedle-mediated RNAi aimed at enhancing its proliferative capacity, necessary for tissue regeneration. Here we develop a strategy for siRNA nanoninjection of the human corneal endothelium. We show that nanoneedles can deliver p16-targeting siRNA to primary human corneal endothelial cells in vitro without toxicity. The nanoinjection of siRNA induces p16 silencing and increases cell proliferation, as monitored by ki67 expression. Furthermore, siRNA nanoinjection targeting the human corneal endothelium is non-toxic ex vivo and silences p16 in transfected cells. These data indicate that nanoinjection can support targeted RNAi therapy for the treatment of endothelial corneal dysfunction.
G1-Cyclin2 (Cln2) promotes chromosome hypercondensation in eco1/ctf7 rad61 null cells during hyperthermic stress in Saccharomyces cerevisiae
Authors: Buskirk Sean , Skibbens Robert V. 
Published: May 2022

ABSTRACTEco1/Ctf7 is a highly conserved acetyltransferase that activates cohesin complexes and is critical for sister chromatid cohesion, chromosome condensation, DNA damage repair, nucleolar integrity, and gene transcription. Mutations in the human homolog of ECO1 (ESCO2/EFO2), or in genes that encode cohesin subunits, result in severe developmental abnormalities and intellectual disabilities referred to as Roberts Syndrome (RBS) and Cornelia de Lange Syndrome (CdLS), respectively. In yeast, deletion of ECO1 results in cell inviability. Co-deletion of RAD61 (WAPL in humans), however, produces viable yeast cells. These eco1 rad61 double mutants, however, exhibit a severe temperature-sensitive growth defect, suggesting that Eco1 or cohesins respond to hyperthermic stress through a mechanism that occurs independent of Rad61. Here, we report that deletion of the G1 cyclin CLN2 rescues the temperature sensitive lethality otherwise exhibited by eco1 rad61 mutant cells, such that the triple mutant cells exhibit robust growth over a broad range of temperatures. While Cln1, Cln2 and Cln3 are functionally redundant G1 cyclins, neither CLN1 nor CLN3 deletions rescue the temperature-sensitive growth defects otherwise exhibited by eco1 rad61 double mutants. We further provide evidence that CLN2 deletion rescues hyperthermic growth defects independent of START and impacts the state of chromosome condensation. These findings reveal novel roles for Cln2 that are unique among the G1 cyclin family and appear critical for cohesin regulation during hyperthermic stress.
An Empirical Bayes Method for Differential Expression Analysis of Single Cells with Deep Generative Models
Authors: Boyeau Pierre , Regier Jeffrey , Gayoso Adam , Jordan Michael I. , Lopez Romain , Yosef Nir 
Published: May 2022

AbstractDetecting differentially expressed genes is important for characterizing subpopulations of cells. In scRNA-seq data, however, nuisance variation due to technical factors like sequencing depth and RNA capture efficiency obscures the underlying biological signal. Deep generative models have been extensively applied to scRNA-seq data, with a special focus on embedding cells into a low-dimensional latent space and correcting for batch effects. However, little attention has been given to the problem of utilizing the uncertainty from the deep generative model for differential expression. Furthermore, the existing approaches do not allow controlling for the effect size or the false discovery rate. Here, we present lvm-DE, a generic Bayesian approach for performing differential expression from using a fitted deep generative model, while controlling the false discovery rate. We apply the lvm-DE framework to scVI and scSphere, two deep generative models. The resulting approaches outperform the state-of-the-art methods at estimating the log fold change in gene expression levels, as well as detecting differentially expressed genes between subpopulations of cells.
Centris pallida(Hymenoptera: Apidae) male body size decreases across five decades
Authors: Barrett Meghan , Johnson Meredith G. 
Published: May 2022

AbstractHistorical data suggest that many bee species have declined in body size. Larger-bodied bees with narrow phenological and dietary breadth are most prone to declines in body size over time. This may be especially true in solitary, desert-adapted species that are vulnerable to climate change – such asCentris pallida(Hymenoptera: Apidae). In addition, body size changes in species with size-linked behaviors could threaten the prevalence of certain behavioral phenotypes long-term.C. pallidasolitary bees are found in the Sonoran Desert. Males use alternative reproductive tactics (ARTs) and are dimorphic in both morphology and behavior.C. pallidamale body size has been studied since the 1970s in the same population. We collected body size data in 2022 and combined it with published records from 1974-2022. We find a persistent decline in the mean head width of patrolling males, and shifts towards smaller body sizes in the populations of males found foraging and hovering. Both morphs declined in average body size, and the proportion of large-morph males in the population decreased by 8%. Mating males did not decline in mean body size over the last five decades. We discuss hypotheses related to the decline inC. pallidamale head width. Finally, we advocate forC. pallidaas an excellent study system for understanding the stability of ARTs with size-linked behavioral phenotypes.
Affinity-optimizing variants within cardiac enhancers disrupt heart development and contribute to cardiac traits
Authors: Jindal Granton A , Bantle Alexis T , Solvason Joe J , Grudzien Jessica L , D’Antonio-Chronowska Agnieszka , Lim Fabian , Le Sophia H , Larsen Reid O , Klie Adam , Frazer Kelly A , Farley Emma K 
Published: May 2022

SummaryEnhancers direct precise gene expression patterns during development and harbor the majority of variants associated with disease. We find that suboptimal affinity ETS transcription factor binding sites are prevalent within Ciona and human developmental heart enhancers. Here we demonstrate in two diverse systems, Ciona intestinalis and human iPSC-derived cardiomyocytes (iPSC-CMs), that single nucleotide changes can optimize the affinity of ETS binding sites, leading to gain-of-function gene expression associated with heart phenotypes. In Ciona, ETS affinity-optimizing SNVs lead to ectopic expression and phenotypic changes including two beating hearts. In human iPSC-CMs, an affinity-optimizing SNV associated with QRS duration occurs within an SCN5A enhancer and leads to increased enhancer activity. Our mechanistic approach provides a much-needed systematic framework that works across different enhancers, cell types and species to pinpoint causal enhancer variants contributing to enhanceropathies, phenotypic diversity and evolutionary changes.In BriefThe prevalent use of low-affinity ETS sites within developmental heart enhancers creates vulnerability within genomes whereby single nucleotide changes can dramatically increase binding affinity, causing gain-of-function enhancer activity that impacts heart development.HighlightsETS affinity-optimizing SNVs can lead to migration defects and a multi-chambered heart.An ETS affinity-optimizing human SNV within an SCN5A enhancer increases expression and is associated with QRS duration.Searching for ETS affinity-optimizing variants is a systematic and generalizable approach to pinpoint causal enhancer variants.
Lingyuanfructus: The First Gymno-angiosperm
Authors: Wang Xin 
Published: May 2022

AbstractDistinct from gymnosperms with naked ovules, angiosperms are defined and characterized by their enclosed ovules. According to Darwinism, angiosperms should be derived from their ancestors that have exposed ovules. Theoretically and precisely, such a plant is expected to have started but not yet completed enclosing its ovules. This expectation is hitherto never met by fossil evidence. Here I report a fossil plant,Lingyuanfructus hibridagen. et sp. nov, from the Yixian Formation (Lower Cretaceous) of Liaoning, China meeting this expectation. With ovules naked and enclosed in a single specimen,Lingyuanfructusblurs the former distinct boundary between angiosperms and gymnosperms.
Genomic analyses of theLinumdistyly supergene reveal convergent evolution at the molecular level
Authors: Gutiérrez-Valencia Juanita , Fracassetti Marco , Berdan Emma L. , Bunikis Ignas , Soler Lucile , Dainat Jacques , Kutschera Verena E. , Losvik Aleksandra , Désamoré Aurélie , Hughes P. William , Foroozani Alireza , Laenen Benjamin , Pesquet Edouard , Abdelaziz Mohamed , Pettersson Olga Vinnere , Nystedt Björn , Brennan Adrian , Arroyo Juan , Slotte Tanja 
Published: May 2022

AbstractSupergenes govern balanced polymorphisms in a wide range of systems. The reciprocal placement of stigmas and anthers in pin and thrum floral morphs of distylous species constitutes an iconic example of a balanced polymorphism governed by a supergene, the distylyS-locus. Recent studies have shown that thePrimulaandTurneradistyly supergenes are both hemizygous in thrums, but it remains unknown if hemizygosity is pervasive among distylyS-loci. Here we have characterized the genetic architecture and evolution of the distyly supergene inLinumby generating a chromosome-level genome assembly ofLinum tenue, followed by the identification of theS-locus using population genomic data. We show that hemizygosity and thrum-specific expression ofS-linked genes, including a pistil-expressed candidate gene for style length, are major features of theLinum S-locus. Structural variation is likely instrumental for recombination suppression, and although the non-recombining dominant haplotype has accumulated transposable elements,S-linked genes are not under relaxed purifying selection. Our findings reveal remarkable convergence in the genetic architecture and evolution of independently derived distyly supergenes. The chromosome-level genome assembly and detailed characterization of the distylyS-locus inL. tenuewill facilitate elucidation of molecular mechanisms underlying the different forms of flowers described by Darwin.
Orchestration of alternative splicing regulates bone marrow mesenchymal stem cells fate during aging
Authors: Xiao Ye , Cai Guang-Ping , Feng Xu , Guo Qi , Huang Yan , Su Tian , Li Chang-Jun , Luo Xiang-Hang , Zheng Yong-Jun , Yang Mi 
Published: May 2022

AbstractSenescence and change of differentiation direction in bone marrow stromal cells (BMSCs) are two of the most important causes of age-related bone loss. As an important post-transcriptional regulatory pathway, alternative splicing (AS) regulates diversity of gene expression. However, the role of AS in BMSCs during aging remains poorly defined. Here we identify AS in specific genes disrupt gene expression pattern and result in age-related debility of BMSCs. We demonstrate the deficiency of splicing factor Y-box protein 1 (YBX1) result in mis-splicing in genes such as Fn1, Taz, Sirt2 and Sp7, further contributing to senescence and shift in differentiation direction of BMSCs during aging. Deletion or over-expression of YBX1 in BMSCs accelerate bone loss or stimulate bone formation in mice. Notably, we identify a small compound sciadopitysin which attenuate the degradation of YBX1 and attenuate bone loss in old mice. Our study demonstrates elaborately controlled RNA splicing governs cell fate of BMSCs and provides a potential therapeutic target for age-related osteoporosis.SummaryThis study demonstrates that YBX1 deficiency induces pre-mRNA mis-splicing and causes senescence and shift in differentiation direction of BMSCs and further accelerates aging-related bone loss. This study identifies Sciadopitysin could reverse this process by targeting YBX1.
Deciphering Hierarchical Chromatin Domains and Preference of Genomic Position Forming Boundaries in Single Mouse Embryonic Stem Cells
Authors: Ye Yusen , Zhang Shihua , Gao Lin , Zhu Yuqing , Zhang Jin 
Published: May 2022

AbstractThe exploration of single-cell 3D genome maps reveals that chromatin domains are indeed physical structures presenting in single cells and domain boundaries vary from cell to cell. However, exhaustive analysis of regulatory factor binding or elements for preference of the formation of chromatin domains in single cells has not yet emerged. To this end, we first develop a hierarchical chromatin domain structure identification algorithm (named as HiCS) from individual single-cell Hi-C maps, with superior performance in both accuracy and efficiency. The results suggest that in addition to the known CTCF-cohesin complex, Polycomb, TrxG, pluripotent protein families and other multiple factors also contribute to shaping chromatin domain boundaries in single embryonic stem cells. Different cooperation patterns of regulatory factors decipher the preference of genomic position categories forming boundaries. And the most extensive six types of retrotransposons differentially distributed in these genomic position categories with preferential localization.
Skeletal muscle Nox4 knockout prevents and Nox2 knockout blunts loss of maximal diaphragm force in mice with heart failure with reduced ejection fraction
Authors: Kumar Ravi A. , Hahn Dongwoo , Kelley Rachel C. , Muscato Derek R. , Shamoun Alex , Curbelo-Bermudez Nuria , Butler W. Greyson , Yegorova Svetlana , Ryan Terence E. , Ferreira Leonardo F. 
Published: May 2022

AbstractPatients with heart failure with reduced ejection fraction (HFrEF) experience diaphragm weakness that contributes to the primary disease symptoms of fatigue, dyspnea, and exercise intolerance. Weakness in the diaphragm is related to excessive production of reactive oxygen species (ROS), but the exact source of ROS remains unknown. NAD(P)H Oxidases (Nox), particularly the Nox2 and 4 isoforms, are important sources of ROS within skeletal muscle that contribute to optimal cell function. There are reports of increased Nox activity in the diaphragm of patients and animal models of HFrEF, implicating these complexes as possible sources of diaphragm dysfunction in HFrEF. To investigate the role of these proteins on diaphragm weakness in HFrEF, we generated inducible skeletal muscle specific knockouts of Nox2 or Nox4 using the Cre-Lox system and assessed diaphragm function in a mouse model of HFrEF induced by myocardial infarction. Diaphragm maximal specific force measuredin vitrowas depressed by ~20% with HFrEF. Knockout of Nox4 provided full protection against the loss of maximal force (p< 0.01), while the knockout of Nox2 provided partial protection (7% depression,p< 0.01). Mitochondrial respiration measured in permeabilized diaphragm muscle bundles increased with HFrEF or the knockout of Nox4 from skeletal muscle fibers (p< 0.05). Knockout of Nox2 from skeletal myofibers improved survival from 50 to 80% following myocardial infarction (p= 0.026). Our findings show an important role for skeletal muscle NAD(P)H Oxidases contributing to loss of diaphragm maximal force in HFrEF, along with systemic pathophysiological responses following myocardial infarction.
Spatial differentiation of background matching strategies along a Late Pleistocene range expansion route
Authors: Spadavecchia Giada , Chiocchio Andrea , Costantini David , Liparoto Anita , Bisconti Roberta , Canestrelli Daniele 
Published: May 2022

AbstractLate Pleistocene climate changes have deeply impacted the range dynamics of temperate species. While the genetic legacy of these dynamics has been widely investigated, little is known about their phenotypic consequences. Anti-predatory strategies offer intriguing opportunities to study phenotypic evolution in response to dispersal dynamics since the ability to avoid predation can be pivotal for populations colonizing new environments. Here we investigated the spatial differentiation of background colour matching strategies along a Late Pleistocene range expansion route of a temperate species, the Tyrrhenian tree frogHyla sarda. Using common-garden experiments, we investigated whether individuals sampled in the source area (Sardinia) and individuals sampled in the newly founded area (Corsica) differ in two components of the camouflage strategy: colour change abilities and background choice behaviour. We found a remarkable spatial structure in both colour change abilities and background choice behaviour, across the expansion range. Tree frogs from the source area displayed higher colour change abilities and a more pronounced preference for a greener background, with respect to tree frogs from the newly colonized area. We discuss these results in the context of the spatial and demographic components of the expansion dynamics. Our results support the intriguing hypothesis that Late Pleistocene biogeographic history might be an overlooked major player in shaping current spatial patterns of phenotypic traits variation across animal populations.
Mapping the epitopes of the Human Leukocyte Antigen E antibodies 3D12 and 4D12
Authors: Brackenridge Simon , Borrow Persephone , McMichael Andrew J. 
Published: May 2022

ABSTRACTThe commonly used commercially available antibodies 3D12 and 4D12 recognise the human leukocyte antigen E (HLA-E) protein. 3D12 is known to exhibit minimal cross-reactivity with classical HLA-Ia allotypes and we confirm that this is also the case for 4D12. These antibodies bind different epitopes on HLA-E, and differ in their ability to recognise alleles of the major histocompatibility complex E (MHC-E) proteins of rhesus and cynomolgus macaques. Using hybrids of different MHC-E alleles, we have mapped the regions that are critical for the binding of these two antibodies. 3D12 recognises a region on the alpha 3 domain that is unique to HLA-E, on the opposite side to that bound by β2-microglobulin, while 4D12 recognises the start of the alpha 2 domain, adjacent to the C terminus of the presented peptide. Knowledge of the binding sites of these two antibodies will facilitate selection of the best antibody for a given application, and inform interpretation of the resulting data.
OntoContext, a new python package for gene contextualization based on the annotation of biomedical texts
Authors: Bedhiafi Walid , Thomas-Vaslin Véronique , Benammar Elgaaied Amel , Six Adrien 
Published: May 2022

AbstractMotivationThe automatic mining for bibliography exploitation in given contexts is a challenge according to the increasing number of scientific publications and new concepts. Several indexing systems were developed for biomedical literature. However, such systems have failed to produce contextualised research of genes and proteins and automatically group texts according to shared concepts. In this paper, we present OntoContext, a contextualization system crossing the use of biomedical ontologies to annotate texts containing terms related to cell populations, anatomical locations and diseases and to extract gene, RNA or protein names in these contexts.ResultsOntoContext, a new python package contains two modules. The “annot” module for “annotation” function, is based on combination of morphosyntactic labelling and exact matching and on dictionaries derived from the Cell Ontology, the UBERON Ontology (anatomical context), the Human Disease Ontology and geniatagger, (which contains particular tags for gene-related names). The “annot” output is used as input for the second module “crisscross” generating lists of gene-related names obtained by crossing annotations from the three mentioned ontologies. OntoContext showed better performances than NCBO Annotator after evaluation on two text corpuses. OntoContext is freely available in the pypi.Availabilityhttps://pypi.python.org/pypi/OntoContext and https://github.com/walidbedhiafi/OntoContext1.Contactadrien.six@sorbonne-universite.fr
Neurologically healthy humans’ ability to make saccades toward unseen targets
Authors: Olkoniemi Henri , Hurme Mikko , Railo Henry 
Published: May 2022

AbstractSome patients with a visual field loss due to a lesion in the primary visual cortex (V1) can shift their gaze to stimuli presented in their blind visual field. The extent to which a similar “blindsight” capacity is present in neurologically healthy individuals remains unknown. Using retinotopically navigated transcranial magnetic stimulation (TMS) of V1 (Experiment 1) and metacontrast masking (Experiment 2) to suppress conscious vision, we examined neurologically healthy humans’ ability to make saccadic eye movements toward visual targets that they reported not seeing. In the TMS experiment, the participants were more likely to initiate a saccade when a stimulus was presented, and they reported not seeing it, than in trials which no stimulus was presented. However, this happened only in a very small proportion (~8%) of unseen trials, suggesting that saccadic reactions were largely based on conscious perception. In both experiments, saccade landing location was influenced by unconscious information: When the participants denied seeing the target but made a saccade, the saccade was made toward the correct location (TMS: 68%, metacontrast: 63%) more often than predicted by chance. Signal detection theoretic measures suggested that in the TMS experiment, saccades toward unseen targets may have been based on weak conscious experiences. In both experiments, reduced visibility of the target stimulus was associated with slower and less precise gaze shifts. These results suggest that saccades made by neurologically healthy humans may be influenced by unconscious information, although the initiation of saccades is largely based on conscious vision.