bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying malaria acquired during travel and its role in malaria elimination on Bioko Island
Authors: Citron Daniel T , Guerra Carlos A , García Guillermo A , Wu Sean L , Battle Katherine E , Gibson Harry S , Smith David L 
Published: April 2021

AbstractBackgroundMalaria elimination is the goal for Bioko Island, Equatorial Guinea. Intensive interventions implemented since 2004 have reduced prevalence, but progress has stalled in recent years. A challenge for elimination has been malaria infections in residents acquired during travel to mainland Equatorial Guinea. We quantify how off-island contributes to remaining malaria prevalence on Bioko Island, and investigate the potential role of a pre-erythrocytic vaccine in making further progress towards elimination.MethodsWe simulated malaria transmission on Bioko Island using a model calibrated based on data from the Malaria Indicator Surveys (MIS) from 2015-2018, including detailed travel histories and malaria positivity by rapid-diagnostic tests (RDTs), as well as geospatial estimates of malaria prevalence. Mosquito population density was adjusted to fit local transmission, conditional on importation rates under current levels of control and within-island mobility. We evaluated the impact of two pre-erythrocytic vaccine distribution strategies: mass treat and vaccinate, and prophylactic vaccination for off-island travelers. We propagated uncertainty through the model through an ensemble of simulations fit to the Bayesian joint posterior probability distribution of the geospatial prevalence estimates.ResultsThe simulations suggest that in Malabo, an urban city containing 80% of the population, there are some pockets of residual transmission, but a large proportion of prevalence is attributable to malaria importation by travelers. Outside of Malabo, prevalence was mainly attributable to local transmission. We assess the uncertainty in the local transmission vs. importation to be lowest within Malabo and highest outside. Using a pre-erythrocytic vaccine to protect travelers would have larger benefits than using the vaccine to protect residents of Bioko Island from local transmission. In simulations, mass treatment and vaccination had short-lived benefits, as malaria prevalence returned to current levels as the vaccine’s efficacy waned. Prophylactic vaccination of travelers resulted in longer-lasting reductions in prevalence. These projections were robust to underlying uncertainty in prevalence estimates.ConclusionsThe modeled outcomes suggest that the volume of malaria cases imported from the mainland is a partial driver of continued endemic malaria on Bioko Island, and that continued elimination efforts on must account for human travel activity.
Direct fast estimator for recombination frequency in the F2cross
Authors: Lorieux Mathias 
Published: April 2021

AbstractIn this short note, a new unbiased maximum-likelihood estimator is proposed for the recombination frequency in the F2cross. The estimator is much faster to calculate than its EM algorithm equivalent, yet as efficient. Simulation studies are carried to illustrate the gain over another simple estimate proposed by Benito & Gallego (2004).
Bacterial bioconvection confers context-dependent growth benefits and is robust under varying metabolic and genetic conditions
Authors: Shoup Daniel , Ursell Tristan 
Published: April 2021

AbstractMicrobial communities often respond to environmental cues by adopting collective behaviors—like biofilms or swarming—that benefit the population. Bioconvection is a distinct and robust collective behavior wherein microbes locally gather into dense groups and subsequently plume downward through fluid environments, driving flow and mixing on scales thousands of times larger than an individual cell. Though bioconvection was observed more than 100 years ago, effects of differing physical and chemical inputs, as well as its potential selective advantages to different species of microbes, remain largely unexplored. In the canonical microbial bioconvectorBacillus subtilis, density inversions that drive this flow are setup by vertically oriented oxygen gradients that originate from an air-liquid interface. In this work, we developEscherichia colias a complementary model organism for the study of bioconvection. We show that forE. coliandB. subtilis, bioconvection confers a context-dependent growth benefit with clear genetic correlates to motility and chemotaxis. We found that fluid depth, cell concentration, and carbon availability have complimentary effects on the emergence and timing of bioconvective patterns, and whereas oxygen gradients are required forB. subtilisbioconvection, we found thatE. colideficient in aerotaxis (Δaer) or energy-taxis (Δtsr) still bioconvect, as do cultures that lack an air-liquid interface. Thus, in two distantly related microbes, bioconvection confers context-dependent growth benefits, andE. colibioconvection is robustly elicited by multiple types of chemotaxis. These results greatly expand the set of physical and metabolic conditions in which this striking collective behavior can be expected and demonstrate its potential to be a generic force for behavioral selection across ecological contexts.
Optogenetic control of apical constriction induces synthetic morphogenesis in mammalian tissues
Authors: Martínez-Ara Guillermo , Taberner Núria , Takayama Mami , Sandaltzopoulou Elissavet , Villava Casandra E. , Takata Nozomu , Eiraku Mototsugu , Ebisuya Miki 
Published: April 2021

ABSTRACTDuring embryonic development, cellular forces synchronize in space and time to generate functional tissue shapes. Apical constriction is one of these force-generating processes, and it is necessary to modulate epithelial curvature in fundamental morphogenetic events, such as neural tube folding. The emerging field of synthetic developmental biology proposes bottom-up approaches to examine the contribution of each cellular process to complex morphogenesis. However, the shortage of tools to manipulate three-dimensional (3D) shapes of mammalian tissues currently hinders the progress of the field. Here we report the development of “OptoShroom3”, a new optogenetic tool that achieves fast spatiotemporal control of apical constriction in mammalian epithelia. Activation of OptoShroom3 through illumination of individual cells in an epithelial cell sheet reduced their apical surface while illumination of groups of cells caused deformation in the adjacent regions. By using OptoShroom3, we further manipulated 3D tissue shapes. Light-induced apical constriction provoked the folding of epithelial cell colonies on soft gels. Its application to murine and human neural organoids led to thickening of neuroepithelia, apical lumen reduction in optic vesicles, and flattening in neuroectodermal tissues. These results show that spatiotemporal control of apical constriction can trigger several types of 3D deformation depending on the initial tissue context.
Whole Brain Correlates of Individual Differences in Skin Conductance Responses during Human Fear Conditioning
Authors: Vinberg Kevin , Rosén Jörgen , Kastrati Granit , Åhs Fredrik 
Published: April 2021

AbstractUnderstanding the neural basis for individual differences in the conditioned skin conductance response (SCR) may inform on autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in conditioned SCR and neural activity throughout the whole brain by using data from a large functional magnetic resonance imaging study (N= 285). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe and midbrain. A ROI analysis replicated a correlation between amygdala activity and conditioned SCR, but amygdala contribution to SCR was modest compared with other regions. We suggest that implicated neural regions belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.
Force field parameters for Fe2+4S2-4 clusters of dihydropyrimidine dehydrogenase, the 5-fluorouracil cancer drug deactivation protein: a step towards in silico pharmacogenomics studies
Authors: Tendwa Maureen Bilinga , Chebon-Bore Lorna , Lobb Kevin , Musyoka Thommas Mutemi , Bishop Özlem Tastan 
Published: April 2021

AbstractThe dimeric dihydropyrimidine dehydrogenase (DPD) metalloenzyme, an adjunct anti-cancer drug target contains highly specialized 4 × Fe2+4S2-4 clusters per chain. These clusters facilitate the catalysis of the rate-limiting step in the pyrimidine degradation pathway through a harmonized electron transfer cascade that triggers a redox catabolic reaction. In the process, majority of administered 5-fluorouracil (5-FU) cancer drug is inactivated while a small proportion is activated to nucleic acid antimetabolites. The occurrence of missense mutations in DPD protein within the general population, including those of African descent, has adverse toxicity effects due to altered 5-FU metabolism. Thus, deciphering mutation effects on protein structure and function is vital, especially for precision medicine purposes. We previously proposed combined molecular dynamics (MD) and dynamic residue network (DRN) analysis to decipher the molecular mechanisms of missense mutations in other proteins. However, the presence of Fe2+4S2-4 clusters in DPD poses a challenge for such in silico studies. The existing AMBER force field parameters cannot accurately describe the Fe2+ center coordination exhibited by this enzyme. Therefore, this study aimed to derive AMBER force field parameters for DPD enzyme Fe2+ centers, using the original Seminario method and collation features Visual Force Field Derivation Toolkit as a supportive approach. All-atom MD simulations were performed to validate the results. Both approaches generated similar force field parameters which accurately described the human DPD protein Fe2+4S2-4 clusters architecture. This information is crucial and opens new avenues for in silico cancer pharmacogenomics and drug discovery related research on 5-FU drug efficacy and toxicity issues.
Normal development of the brain: a survey of joint structural-functional brain studies
Authors: Namiranian Roxana , Malakshan Sahar Rahimi , Moghaddam Hamid Abrishami , Khadem Ali , Jafari Reza 
Published: April 2021

AbstractJoint structural-functional (S-F) developmental studies present a novel approach to address the complex neuroscience questions on how the human brain works and how it matures. Joint S-F biomarkers have the inherent potential to model effectively the brain’s maturation, fill the information gap in temporal brain atlases, and demonstrate how the brain’s performance matures during the lifespan. This review presents the current state of knowledge on heterochronous and heterogeneous development of S-F links during the maturation period. The S-F relationship has been investigated in early-matured unimodal and prolonged-matured transmodal regions of the brain using a variety of structural and functional biomarkers and data acquisition modalities. Joint S-F unimodal studies have employed auditory and visual stimuli, while the main focus of joint S-F transmodal studies has been resting-state networks and working memory. However, non-significant associations between some structural and functional biomarkers and their maturation show that designing and developing effective S-F biomarkers is still a challenge in the field. Maturational characteristics of brain asymmetries have been poorly investigated by the joint S-F studies, and the results were inconsistent with previous non-joint ones. The inherent complexity of the brain performance can be modeled using multifactorial and nonlinear techniques as promising methods to simulate the impact of age on S-F relations considering their analysis challenges.
Humans postural sways: non-Gauss, variability, and aging aspects of a data set mining
Authors: Chuiko Gennady P. , Darnapuk Yevhen S. , Dvornik Olga V. , Krainyk Yaroslav M. , Yaremchuk Olga M. 
Published: April 2021

AbstractThis report presents the results of data mining of a sample with two focus-groups. They have the same sizes: seven people into each one, random-wise picked up from the same data set. The trials of groups were idem. The postural swings, that is, the move of the center-of-pressure (COP), were recorded. Maple, a computer math system, has allowed us to apply the Principal Components Analysis, Statistical analysis, Kernel Density Estimations (KDE) for the probabilities. Poincare and Recurrence Plots were other tools for modern data mining. The non-Gauss features of the real distributions are not that to be neglect. They exist not only as outliers but as sharp kurtosis and skewness. Still, they are so far not enow to grave doubts to the Fractional Brownian model. We found some subtle aging hallmarks for focus-groups. First, the trend of variability descriptors to be bi-modal is sheerer for the older group. Second, the coefficients of correlations of the short-time variability index with other descriptors are clear age-related.2012 ACM Subject ClassificationApplied computing → Life and medical sciences → Health informatics
ipmr: Flexibly implement Integral Projection Models in R
Authors: Levin Sam C. , Childs Dylan Z. , Compagnoni Aldo , Evers Sanne , Knight Tiffany M. , Salguero-Gómez Roberto 
Published: April 2021

AbstractIntegral projection models (IPMs) are an important tool for studying the dynamics of populations structured by one or more continuous traits (e.g.size, height, color). Researchers use IPMs to investigate questions ranging from linking drivers to plant population dynamics, planning conservation and management strategies, and quantifying selective pressures in natural populations. The popularity of stage-structured population models has been supported byRscripts and packages (e.g.IPMpack, popbio, popdemo, lefko3) aimed at ecologists, which have introduced a broad repertoire of functionality and outputs. However, pressing ecological, evolutionary, and conservation biology topics require developing more complex IPMs, and considerably more expertise to implement them. Here, we introduceipmr, a flexibleRpackage for building, analyzing, and interpreting IPMs.Theipmrframework relies on the mathematical notation of the models to express them in code format. Additionally, this package decouples the model parameterization step from the model implementation step. The latter point substantially increasesipmr’s flexibility to model complex life cycles and demographic processes.ipmrcan handle a wide variety of models, including density dependence, discretely and continuously varying stochastic environments, and multiple continuous and/or discrete traits.ipmrcan accommodate models with individuals cross-classified by age and size. Furthermore, the package provides methods for demographic analyses (e.g.asymptotic and stochastic growth rates) and visualization (e.g.kernel plotting).ipmris a flexibleRpackage for integral projection models. The package substantially reduces the amount of time required to implement general IPMs. We also provide extensive documentation with six vignettes and help files, accessible from anRsession and online.
Repeated strand invasion and extensive branch migration are hallmarks of meiotic recombination
Authors: Ahuja Jasvinder S. , Harvey Catherine S. , Wheeler David L. , Lichten Michael 
Published: April 2021

AbstractCurrently favored models for meiotic recombination posit that both noncrossover and crossover recombination are initiated by DNA double strand breaks but form by different mechanisms, noncrossovers by synthesis dependent strand annealing, and crossovers by formation and resolution of double Holliday junctions centered around the break. This dual mechanism hypothesis predicts different hybrid DNA patterns in noncrossover and crossover recombinants. We show that these predictions are not upheld, by mapping with unprecedented resolution, parental strand contributions to recombinants at a model locus. Instead, break repair in both noncrossovers and crossovers involves synthesis-dependent strand annealing, often with multiple rounds of strand invasion. Crossover-specific double Holliday junction formation occurs via processes that involve branch migration as an integral feature and that can be separated from break repair itself. These findings reveal meiotic recombination to be a highly dynamic process and prompt a new view of the relationship between crossover and noncrossover recombination.
Differences between apoplastic and cytosolic reactive oxygen species production inArabidopsisduring pattern-triggered immunity
Authors: Arnaud Dominique , Deeks Michael J. , Smirnoff Nicholas 
Published: April 2021

AbstractDespite an ever-increasing interest in reactive oxygen species (ROS) signalling during plant-microbe interactions, very little information exists, mainly for technical reasons, on the molecular mechanisms regulating intracellular hydrogen peroxide (H2O2) signalling during PAMP-triggered immunity. Here, we used a sensitive fluorimetry method and the H2O2sensor roGFP2-Orp1, which revealed unsuspected features on the regulation of cytoplasmic H2O2and thiol redox dynamics upon pathogen-associated molecular patterns (PAMPs) perception byArabidopsis thaliana. Extended PAMP-induced cytosolic roGFP2-Orp1 oxidation was distinct from the transient oxidative burst in the apoplast measured by luminol oxidation. Pharmacological and genetic analyses indicate that the prolonged PAMP-induced H2O2increase in the cytoplasm was largely independent on NADPH oxidases and apoplastic peroxidases. By contrast, the NADPH oxidase mutantrbohFwas hyper-sensitive to roGFP2-Orp1 oxidation by H2O2and PAMP indicating a lower antioxidant capacity. Unlike previous reports, therbohFmutant, but notrbohD, was impaired in PAMP-triggered stomatal closure and ROS production measured by a fluorescein-based probe in guard cells resulting in defects in stomatal defences against bacteria. However, stomatal closure was not correlated with an increase in roGFP2-Orp1 oxidation in guard cells. Interestingly, RBOHF also participated in PAMP-induced apoplastic alkalinisation. Altogether, our results provide novel insights on the interplay between apoplastic and cytosolic ROS dynamics and highlight the importance of RBOHF in plant immunity.Significance statementPlants mount defence responses to pathogens by detecting pathogen-associated molecular patterns (PAMPs). One response is a rapid and transient burst of reactive oxygen species (ROS, e.g. superoxide and hydrogen peroxide) in the cell wall (apoplast) produced by NADPH oxidases and cell wall peroxidases. Using a genetically-encoded hydrogen peroxide sensor roGFP2-Orp1, we found that, in contrast to the transient apoplastic ROS burst, there is also prolonged hydrogen peroxide production in the cytosol upon PAMP perception which is independent of NADPH oxidase and cell wall peroxidases. Our results suggest that apoplastic ROS rather than intracellular hydrogen peroxide is a signal triggering stomatal closure during PAMP-triggered immunity. Additionally, we re-address the relative contribution of the NADPH oxidases D and F in stomatal immunity.
Highly task-specific and distributed neural connectivity in working memory revealed by single-trial decoding in mice and humans
Authors: Strahnen Daniel , Kapanaiah Sampath K.T. , Bygrave Alexei M. , Liss Birgit , Bannerman David M. , Akam Thomas , Grewe Benjamin F. , Johnson Elizabeth L. , Kätzel Dennis 
Published: April 2021

AbstractWorking memory (WM), the capacity to briefly and intentionally maintain mental items, is key to successful goal-directed behaviour and impaired in a range of psychiatric disorders. To date, several brain regions, connections, and types of neural activity have been correlatively associated with WM performance. However, no unifying framework to integrate these findings exits, as the degree of their species- and task-specificity remains unclear. Here, we investigate WM correlates in three task paradigms each in mice and humans, with simultaneous multi-site electrophysiological recordings. We developed a machine learning-based approach to decode WM-mediated choices in individual trials across subjects from hundreds of electrophysiological measures of neural connectivity with up to 90% prediction accuracy. Relying on predictive power as indicator of correlates of psychological functions, we unveiled a large number of task phase-specific WM-related connectivity from analysis of predictor weights in an unbiased manner. Only a few common connectivity patterns emerged across tasks. In rodents, these were thalamus-prefrontal cortex delta- and beta-frequency connectivity during memory encoding and maintenance, respectively, and hippocampal-prefrontal delta- and theta-range coupling during retrieval, in rodents. In humans, task-independent WM correlates were exclusively in the gamma-band. Mostly, however, the predictive activity patterns were unexpectedly specific to each task and always widely distributed across brain regions. Our results suggest that individual tasks cannot be used to uncover generic physiological correlates of the psychological construct termed WM and call for a new conceptualization of this cognitive domain in translational psychiatry.
Stitching and registering highly multiplexed whole slide images of tissues and tumors using ASHLAR
Authors: Muhlich Jeremy L. , Chen Yu-An , Yapp Clarence , Russell Douglas , Santagata Sandro , Sorger Peter K 
Published: April 2021

ABSTRACTMotivationStitching microscope images into a mosaic is an essential step in the analysis and visualization of large biological specimens, particularly human and animal tissues. Recent approaches to highly-multiplexed imaging generate high-plex data from sequential rounds of lower-plex imaging. These multiplexed imaging methods promise to yield precise molecular single-cell data and information on cellular neighborhoods and tissue architecture. However, attaining mosaic images with single-cell accuracy requires robust image stitching and image registration capabilities that are not met by existing methods.ResultsWe describe the development and testing of ASHLAR, a Python tool for coordinated stitching and registration of 103or more individual multiplexed images to generate accurate whole-slide mosaics. ASHLAR reads image formats from most commercial microscopes and slide scanners, and we show that it performs better than existing open source and commercial software. ASHLAR outputs standard OME-TIFF images that are ready for analysis by other open-source tools and recently developed image analysis pipelines.Availability and implementationASHLAR is written in Python and available under an MIT license athttps://github.com/labsyspharm/ashlar. An informational website with user guides and test data is available athttps://labsyspharm.github.io/ashlar/.