bluuebunny/crossref_metadata_2025_split huggingface dataset:
TATTOO-seq delineates spatial and cell type-specific regulatory programs during limb patterning
Authors: Bastide Sébastien , Chomsky Elad , Saudemont Baptiste , Loe-Mie Yann , Schmutz Sandrine , Novault Sophie , Marlow Heather , Tanay Amos , Spitz François 
Published: March 2022

AbstractThe coordinated differentiation of progenitor cells into specialized cell types and their spatial organization into distinct domains is central to embryogenesis. Here, we applied a new unbiased spatially resolved single-cell transcriptomics method to identify the genetic programs that underlie the emergence of specialized cell types during limb development and their integration in space. We uncovered combinations of transcription factors whose expression patterns are predominantly associated with cell type specification or spatial position, enabling the deconvolution of cell fate and position identity. We demonstrate that the embryonic limb undergoes a complex multi-scale re-organization upon perturbation of one of its spatial organizing centers, including the loss of specific cell populations, specific alterations in the molecular identities of other pre-existing cell states and changes in their relative spatial distribution. Altogether, our study shows how multi-dimensional single-cell and spatially resolved molecular atlases could reveal the interconnected genetic networks that regulate the intricacies of organogenesis and its reorganization upon genetic alterations.
The dynamics of speciation in the gall-forming aphidGeoicaspp. within and amongPistaciahost tree species
Authors: Ben-Shlomo Rachel , Talal Stav , Inbar Moshe 
Published: March 2022

ABSTRACTTrees of the genusPistaciaserve as obligate hosts for gall-forming aphids (Hemiptera, Aphididae, Fordini). Each aphid species induces a characteristic gall on a singlePistaciahost species. The genusGeoica(Fordini) induce similar spherical closed galls on the lower side of the leaflet’s midvein, on differentPistaciaspecies. Two species ofPistaciatrees that harborGeoicagalls grow naturally in Israel:P.palaestinaandP. atlantica.We analyzed the phylogeny and the genetic structure of theGeoicaspecies complex in Israel, and assessed the genetic differentiation and the level of host plant specificity of the aphids betweenP.atlanticaandP. palaestina. We found that the splitting of the genus betweenP. atlanticaandP. palaestinais estimated to have occurred 24–25 Ma (the Oligocene/Miocene boundary). Five different haplotypes suggesting five different species have been further speciating amongGeoicaspp., galling onP. atlantica, and an additional three species, onP. palaestina.Accession Numbers (COI sequences):MW452548 - Pp-Q-7d-Gamla - Haplotype-VIMW452549 - Pp-Q-10b-Gamla - Haplotype-VIIMW452550 - Pp-A-1a-Mezar - Haplotype-VIIMW452551 - Pp-S-6c-Sasa - Haplotype-VIMW452552 - Pp-New Hermon-2-5 - Haplotype-VIIIMW452553 - Pa-Q-10a-II Gamla - Haplotype-IVMW452554 - Pa-Q-5d Gamla - Haplotype-IIMW452555 - Pa-A-2f Mezar - Haplotype-IVMW452556 - Pa-E-13 Anafa - Haplotype-IIIMW452557 - Pa-K-10a Adolam - Haplotype-IVMW452558 - Pa-K-3a Adolam - Haplotype-IIMW452559 - Pa-N-2a Nizana - Haplotype-IMW452560 - Pa-Z-1-3 Hazeva - Haplotype-IMW452561 - Pa-SL-3-3 Jordan-Sela - Haplotype-V
Stroke disconnectome decodes reading networks
Authors: Forkel Stephanie J. , Labache Loïc , Nachev Parashkev , de Schotten Michel Thiebaut , Hesling Isabelle 
Published: March 2022

AbstractCognitive functional neuroimaging has been around for over 30 years and has shed light on the brain areas relevant for reading. However, new methodological developments enable mapping the interaction between functional imaging and the underlying white matter networks. In this study, we used such a novel method, called the disconnectome, to decode the reading circuitry in the brain. We used the resulting disconnection patterns to predict the typical lesion that would lead to reading deficits after brain damage. Our results suggest that white matter connections critical for reading include fronto-parietal U-shaped fibres and the vertical occipital fasciculus (VOF). The lesion most predictive of a reading deficit would impinge on the left temporal, occipital, and inferior parietal gyri. This novel framework can systematically be applied to bridge the gap between the neuropathology of language and cognitive neuroscience.
The effects of explicit and implicit information on modulation of corticospinal excitability during hand-object interactions
Authors: Rens Guy , Davare Marco , van Polanen Vonne 
Published: March 2022

AbstractFingertip force scaling during hand-object interactions typically relies on visual information about the object and sensorimotor memories from previous object interactions. Here, we investigated whether contextual information, that is not explicitly linked to the intrinsic object properties (e.g., size or weight) but is informative for motor control requirements, can mediate force scaling. For this, we relied on two separate behavioral tasks during which we applied transcranial magnetic stimulation (TMS) to probe corticospinal excitability (CSE), as a window onto the primary motor cortex role in controlling fingertip forces. In experiment 1, participants performed a force tracking task, where we manipulated available implicit and explicit visual information. That is, either the force target was fully visible, or only the force error was displayed as a deviation from a horizontal line. We found that participants’ performance was better when the former condition, in which they had explicit access to predictive information. However, we did not find differences in CSE modulation based on the type of visual information. On the other hand, CSE was modulated by the change in muscle contraction, i.e., contraction vs. relaxation and fast vs. slow changes. In sum, these findings indicate that CSE only reflects the ongoing motor command. In experiment 2, other participants performed a sequential object lifting task of visually identical objects that were differently weighted, in a seemingly random order. Within this task, we hid short series of incrementally increasing object weights. This allowed us to investigate whether participants would scale their forces for specific object weights based on the previously lifted object (i.e., sensorimotor effect) or based on the implicit information about the hidden series of incrementally increasing weights (i.e., extrapolation beyond sensorimotor effects). Results showed that participants did not extrapolate fingertip forces based on the hidden series but scaled their forces solely on the previously lifted object. Unsurprisingly, CSE was not modulated differently when lifting series of random weights versus series of increasing weights. Altogether, these results in two different grasping tasks suggest that CSE encodes ongoing motor components but not sensorimotor cues that are hidden within contextual information.HighlightsExplicit visual cues and sensorimotor experience are key for object graspingInvestigating influence of implicit, contextual information on object graspingExplicit but not implicit cues improve motor performance during object graspingExplicit but not implicit cues modulate corticospinal excitability
slendr: a framework for spatio-temporal population genomic simulations on geographic landscapes
Authors: Petr Martin , Haller Benjamin C. , Ralph Peter L. , Racimo Fernando 
Published: March 2022

AbstractOne of the goals of population genetics is to understand how evolutionary forces shape patterns of genetic variation over time. However, because populations evolve across both time and space, most evolutionary processes also have an important spatial component, acting through phenomena such as isolation by distance, local mate choice, or uneven distribution of resources. This spatial dimension is often neglected, partly due to the lack of tools specifically designed for building and evaluating complex spatio-temporal population genetic models. To address this methodological gap, we present a new framework for simulating spatially-explicit genomic data, implemented in a new R package calledslendr(www.slendr.net), which leverages a SLiM simulation back-end script bundled with the package. With this framework, the users can programmatically and visually encode spatial population ranges and their temporal dynamics (i.e., population displacements, expansions, and contractions) either on real Earth landscapes or on abstract custom maps, and schedule splits and gene-flow events between populations using a straightforward declarative language. Additionally,slendrcan simulate data from traditional, non-spatial models, either with SLiM or using an alternative built-in coalescentmsprimeback end. Together with its R-idiomatic interface to thetskitlibrary for tree-sequence processing and analysis,slendropens up the possibility of performing efficient, reproducible simulations of spatio-temporal genomic data entirely within the R environment, leveraging its wealth of libraries for geospatial data analysis, statistics, and visualization. Here, we present the design of theslendrR package and demonstrate its features on several practical example workflows.
A novel method for reliably measuring miniature and spontaneous postsynaptic potentials/currents in whole-cell patch clamp recordings in the central nervous system
Authors: Dervinis Martynas , Major Guy 
Published: March 2022

AbstractMeasurements of miniature postsynaptic currents (mPSCs) or potentials (mPSPs) in the soma of neurons of the central nervous system (CNS) provide a way of quantifying the synaptic function at the network level and, therefore, are routine in the neurophysiology literature. These miniature responses (or minis) are thought to be elicited by the spontaneous release of a single neurotransmitter vesicle, also called quantum. As such their measurement at the soma can potentially offer a technically straightforward way of estimating ‘quantal sizes’ of central synapses. However, popular methods for detecting minis in whole-cell recordings fall short of being able to reliably distinguish them from background physiological noise. This issue has received very limited attention in the literature and its scope as well as the relative performance of existing algorithms have not been quantified. As a result, solutions for reliably measuring the quantal size in somatic recordings also do not exist. As the first step in proposing and testing a potential solution, we developed and described a novel mPSP/mPSC detection algorithm as part of our quantal analysis software called ‘minis’. We tested its performance in detecting real and simulated minis in whole-cell recordings from pyramidal neurons in rat neocortical slices and compared it to two of the most-used mini detection algorithms. This benchmarking revealed superior detection by our algorithm. The release version of the algorithm also offers great flexibility via graphical and programming interfaces.
Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip
Authors: Mahajan Gautam , Doherty Erin , To Tania , Sutherland Arlene , Grant Jennifer , Junaid Abidemi , Gulati Aakanksha , LoGrande Nina Teresa , Izadifar Zohreh , Timilsina Sanjay Sharma , Horváth Viktor , Plebani Roberto , France Michael , Hood-Pishchany Indriati , Rakoff-Nahoum Seth , Kwon Douglas S. , Goyal Girija , Prantil-Baun Rachelle , Ravel Jacques , Ingber Donald E. 
Published: March 2022

ABSTRACTBackgroundA dominance of non-iners Lactobacillus species in the vaginal microbiome is optimal and strongly associated with gynecological and obstetric health, while the presence of diverse obligate or facultative anaerobic bacteria and a paucity in Lactobacillus species, similar to communities found in bacterial vaginosis (BV), is considered non-optimal and associated with adverse health outcomes. Various therapeutic strategies are being explored to modulate the composition of the vaginal microbiome; however, there is no human model that faithfully reproduces the vaginal epithelial microenvironment for preclinical validation of potential therapeutics or testing hypotheses about vaginal epithelium-microbiome interactions.ResultsHere, we describe an organ-on-a-chip (Organ Chip) microfluidic culture model of the human vaginal mucosa (Vagina Chip) that is lined by hormone-sensitive, primary vaginal epithelium interfaced with underlying stromal fibroblasts, which sustains a low physiological oxygen concentration in the epithelial lumen. We show that the Vagina Chip can be used to assess colonization by optimal L. crispatus consortia as well as non-optimal Gardnerella vaginalis-containing consortia, and to measure associated host innate immune responses. Co-culture of the L. crispatus consortia was accompanied by maintenance of epithelial cell viability, accumulation of D- and L-lactic acid, maintenance of a physiologically relevant low pH, and down regulation of proinflammatory cytokines. In contrast, co-culture of G. vaginalis-containing consortia in the Vagina Chip resulted in epithelial cell injury, a rise in pH, and upregulation of proinflammatory cytokines.ConclusionThis study demonstrates the potential of applying human Organ Chip technology to create a preclinical model of the human vaginal mucosa that can be used to better understand interactions between the vaginal microbiome and host tissues, as well as to evaluate the safety and efficacy of live biotherapeutics products.
Target-agnostic discovery of Rett Syndrome therapeutics by coupling computational network analysis and CRISPR-enabled in vivo disease modeling
Authors: Novak R. , Lin T. , Kaushal S. , Sperry M. , Vigneault F. , Gardner E. , Loomba S. , Shcherbina K. , Keshari V. , Dinis A. , Vasan A. , Chandrasekhar V. , Takeda T. , Turner J.R. , Levin M. , Ingber D.E. 
Published: March 2022

ABSTRACTMany neurodevelopmental genetic disorders, such as Rett syndrome, are caused by a single gene mutation but trigger changes in expression and regulation of numerous other genes. This severely impair functions of multiple organs and organ systems beyond the central nervous system (CNS), adding to the challenge of developing broadly effective treatments based on a single drug target. This challenge is further complicated by the lack of sufficiently broad and biologically relevant drug screens, and the inherent complexity in identifying clinically relevant targets responsible for diverse phenotypes. Here, we combined human gene regulatory network-based computational drug prediction with in vivo screening in a population-level diversity, CRISPR-edited, Xenopus laevis tadpole model of Rett syndrome to carry out target-agnostic drug discovery, which rapidly led to the identification of the FDA-approved drug vorinostat as a potential repurposing candidate. Vorinostat broadly improved both CNS and non-CNS (e.g., gastrointestinal, respiratory, inflammatory) abnormalities in a pre-clinical mouse model of Rett syndrome. This is the first Rett syndrome treatment to demonstrate pre-clinical efficacy across multiple organ systems when dosed after the onset of symptoms, and network analysis revealed a putative therapeutic mechanism for its cross-organ normalizing effects based on its impact on acetylation metabolism and post-translational modifications of microtubules. Although traditionally considered an inhibitor of histone deacetylases (HDAC), vorinostat unexpectedly restored protein acetylation across both hypo- and hyperacetylated tissues, suggesting non-HDAC-mediated therapeutic mechanisms supported by proteomic analysis.
Computational exploration of bio-remediation solution for mixed plastic waste
Authors: Sunny  , Maurya Ankita , Vats Mohit Kumar , Khare Sunil Kumar , Srivastava Kinshuk Raj 
Published: March 2022

AbstractThe plastic materials are recalcitrant in the open environment, surviving longer without complete remediation. The current disposal methods of used plastic material are not efficient; consequently, plastic wastes are infiltrating the natural resources of the biosphere. A sustaining solution for plastic waste is either recycling or making it part of the earth’s biogeochemical cycle. We have collected, manually mined, and analyzed the previous reports on plastic biodegradation. Our results demonstrate that the biodegradation pattern of plastics follows the chemical classification of plastic types. Based on clustering analysis, the distant plastic types are grouped into two broad categories of plastic types, C-C (non-hydrolyzable) and C-X (hydrolyzable). The genus enrichment analysis suggests that Pseudomonas and Bacillus from bacteria and Aspergillus and Penicillium from fungal are potential genera for bioremediation of mixed plastic waste. Overall results have pointed towards a possible solution of mixed plastic waste either in a circular economy or open remediation. The meta-analysis of the reports revealed a historical inclination of biodegradation studies towards C-X type of plastic; however, the C-C class is dominated in overall plastic production. An interactive web portal of reports is hosted at plasticbiodegradation.com for easy access by other researchers for future studies
A reinforcement learning algorithm shapes maternal care in mice
Authors: Xie Yunyao , Huang Longwen , Corona Alberto , Pagliaro Alexa H. , Shea Stephen D. 
Published: March 2022

AbstractThe neural substrates for processing classical rewards such as food or drugs of abuse are well-understood. In contrast, the mechanisms by which organisms perceive social contact as rewarding and subsequently modify their interactions are unclear. Here we tracked the gradual emergence of a repetitive and highly-stereotyped parental behavior and show that trial-by-trial performance correlates with the history of midbrain dopamine (DA) neuron activity. We used a novel behavior paradigm to manipulate the subject’s expectation of imminent pup contact and show that DA signals conform to reward prediction error, a fundamental component of reinforcement learning (RL). Finally, closed-loop optogenetic inactivation of DA neurons at the onset of pup contact dramatically slowed emergence of parental care. We conclude that this prosocial behavior is shaped by an RL mechanism in which social contact itself is the primary reward.One-Sentence SummaryMaternal interactions with offspring are shaped by a dopaminergic reinforcement learning mechanism.
Environmental orientation, relational capital and SMEs performance: do religious, cultural and mimetic orientations matter in a Sub-Saharan African economy?
Authors: Baah Charles , Afum Ebenezer , Agyabeng-Mensah Yaw , Dacosta Essel , Opoku-Agyeman Douglas , Nyame Collins 
Published: March 2022

PurposeUsing the institutional and natural resource-based view theories, the purpose of this study is to examine the influence of religious, cultural and mimetic orientations on proactive environmental strategy, corporate environmental responsibility and traditional environmental strategy. Relying on data collected from managers of small and medium-sized enterprises (SMEs), the study further examines how proactive environmental strategy, corporate environmental responsibility and traditional environmental strategy drive relational capital and firm performance of SMEs operating in Ghana.Design/methodology/approachThe study employed a survey research design, a quantitative approach and a partial least square structural equation modelling technique in making data analysis and interpretations due to its appropriateness for predictive research models.FindingsThe results suggest that mimetic orientation robustly and significantly influence the dimensions of environmental orientation. While religious orientation only had a robust and significant influence on proactive environmental strategy, cultural orientation robustly and significantly influences both proactive and traditional environmental strategies. Despite the positive and significant interactions that exist between proactive environmental strategy, corporate environmental responsibility, traditional environmental strategy, relational capital and firm performance, the findings particularly revealed that proactive and environmental strategies insignificantly correlated with relational capital contrary to past study findings.Originality/valueThe study is among the few to examine how religious, cultural and mimetic orientations interrelate with proactive and traditional environmental orientations, relational capital and firm performance in an emerging economy. Based on the findings, implications and directions for future research are discussed while also providing guidance for policymakers, regulatory bodies, scholars and practitioners.
Uncertainty quantification for correlated variables combining p-box with copula upon limited observed data
Authors: Shen Zhanpeng , Zang Chaoping , Chen Xueqian , Hu Shaoquan , Liu Xin-en 
Published: March 2022

PurposeFor fast calculation of complex structure in engineering, correlations among input variables are often ignored in uncertainty propagation, even though the effect of ignoring these correlations on the output uncertainty is unclear. This paper aims to quantify the inputs uncertainty and estimate the correlations among them acorrding to the collected observed data instead of questionable assumptions. Moreover, the small size of the experimental data should also be considered, as it is such a common engineering problem.Design/methodology/approachIn this paper, a novel method of combining p-box with copula function for both uncertainty quantification and correlation estimation is explored. Copula function is utilized to estimate correlations among uncertain inputs based upon the observed data. The p-box method is employed to quantify the input uncertainty as well as the epistemic uncertainty associated with the limited amount of the observed data. Nested Monte Carlo sampling technique is adopted herein to ensure that the propagation is always feasible. In addition, a Kriging model is built up to reduce the computational cost of uncertainty propagation.FindingsTo illustrate the application of this method, an engineering example of structural reliability assessment is performed. The results indicate that it may significantly affect output uncertainty whether to quantify the correlation among input variables. Furthermore, an additional advantage for risk management is obtained in this approach due to the separation of aleatory and epistemic uncertainties.Originality/valueThe proposed method takes advantage of p-box and copula function to deal with the correlations and limited amount of the observed data, which are two important issues of uncertainty quantification in engineering. Thus, it is practical and has the ability to predict accurate response uncertainty or system state.