bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aging modulates the effects of scene complexity on visual search and target selection in virtual environments
Authors: Lachica Isaiah J. , Kalkar Aniruddha , Finley James M. 
Published: May 2023

AbstractProcessing task-relevant visual information is important for successfully completing many everyday tasks. Prior work demonstrated that older adults are more susceptible to distraction by salient stimuli, leading to less efficient visual search. However, these studies often relied on simple stimuli, and little is known about how aging influences visual attention in environments more representative of real-world complexity. Here, we test the hypothesis that aging impacts how the visual complexity of the environment influences visual search. We asked young and older adults to complete a virtual reality-based visual search task with three levels of increasing visual complexity. As visual complexity increased, all participants took longer to complete the task. This increase in time to completion resulted from two factors: an increased time required to transfer gaze from one target to the next as participants re-fixated task-relevant objects and longer lags between when correct targets were fixated and selected. We also found that these changes in gaze trajectory were greater in older adults. In addition, we found that short-term and working memory capacities were positively associated with multiple performance measures in the visual search task. This suggests that visual search performance could be integrated into assessments of working memory in dynamic environments.
De novoassembly of the whole genome of Moth bean (Vigna aconitifolia), an underutilizedVignaspecies of India
Authors: Suranjika Sandhya , Pradhan Seema , Kalia Rajwant K. , Dey Nrisingha 
Published: May 2023

AbstractAs a fast-growing legume species, moth bean (Vigna aconitifolia)has a unique habit of sustaining in conditions of higher temperatures and drought. This grain legume is also valued for it seeds which have one of the highest contents of proteins amongst all grain legumes. This plant can be a rich source of genomic resources, which can be applied to improve abiotic stress response in allied grain legumes and also help understand the biological processes governing their overall development. Here we generate ade novogenome assembly ofVigna aconitifoliausing PacBio High-Fidelity reads and Hi-C sequencing data, with a total size of 409 Mb and contig N50 of more than 30Mb. We also annotated the genome for repeat sequences, found that the moth bean genome comprises of about 54% of repetitive sequences, and predicted 36950 protein-coding genes. Using the available RNA-Seq data for moth bean, we have developed a differential expression profile for various tissues of moth bean using the whole genome as a reference and identified simple sequence repeats that could be developed into viable molecular markers. This nascent study will provide insight into the identification of agronomically important genes and accelerate the genetic improvement of moth bean as well as other legume crops.
Virtual reality empowered deep learning analysis of brain activity
Authors: Kaltenecker Doris , Al-Maskari Rami , Negwer Moritz , Hoeher Luciano , Kofler Florian , Zhao Shan , Todorov Mihail , Paetzold Johannes Christian , Wiestler Benedikt , Geppert Julia , Morigny Pauline , Rohm Maria , Menze Bjoern H. , Herzig Stephan , Berriel Diaz Mauricio , Ertürk Ali 
Published: May 2023

ABSTRACTTissue clearing and fluorescent microscopy are powerful tools for unbiased organ-scale protein expression studies. Critical for interpreting expression patterns of large imaged volumes are reliable quantification methods. Here, we present DELiVR a deep learning pipeline that uses virtual reality (VR)-generated training data to train deep neural networks, and quantify c-Fos as marker for neuronal activity in cleared mouse brains and map its expression at cellular resolution. VR annotation significantly accelerated the speed of generating training data compared to conventional 2D slice based annotation. DELiVR detects cells with much higher precision than current threshold-based pipelines, and provides an extensive toolbox for data visualization, inspection and comparison. We applied DELiVR to profile cancer-related mouse brain activity, and discovered a novel activation pattern that distinguishes between weight-stable cancer and cancer-associated weight loss. Thus, DELiVR provides a robust mouse brain analysis pipeline at cellular scale that can be used to study brain activity patterns in health and disease.The DELiVR software, Fiji plugin and documentation can be found athttps://www.DISCOtechnologies.org/DELiVR/.Graphical AbstractHighlightsDELiVR detects labelled cells in cleared brains with deep learningDELiVR is trained by annotating ground-truth data in virtual reality (VR)DELiVR is launched via a FIJI plugin anywhere from PCs to clustersUsing DELiVR, we found new brain activity patterns in weight-stable vs. cachectic cancerSupplementary Videos can be seen at:https://www.DISCOtechnologies.org/DELiVR/
Severe enamel defects in wild Japanese macaques
Authors: Towle Ian , Loch Carolina , Martínez de Pinillos Marina , Modesto-Mata Mario , Hlusko Leslea J. 
Published: May 2023

AbstractPlane-form enamel hypoplasia (PFEH) is a severe dental defect in which large areas of the crown are devoid of enamel. This condition is rare in humans and rarer in wild primates. The etiology of PFEH has been linked to exposure to severe disease, malnutrition, environmental toxins, and other systemic conditions. Similar defects have also been associated with genetic conditions such as amelogenesis imperfecta. In this study, we examined the prevalence of all types of enamel hypoplasia in several populations of wild Japanese macaques (Macaca fuscata) with the aim of providing context for the severe defects found in macaques from Yakushima Island. We found that macaques from other islands and from the mainland of Japan have low prevalence of the more common types of enamel hypoplasia and none exhibit PFEH. In contrast, 10 of the 21 individuals (48%) from Yakushima Island displayed uniform and significant PFEH, with all 10 living in two adjacent locations in the south of the island. All permanent teeth were affected to varying degrees except for first molars, and the mineral content of the remaining enamel in teeth with PFEH is normal (i.e., no hypo- or hyper mineralization). Given that the affected individuals have smaller first molars compared to non-affected macaques, and that they all underwent dental development during a period of substantial human-related habitat change, we conclude that the PFEH likely resulted from environmental stress. Extreme weather events on the island may also have influenced the formation of these defects. Additionally, it is plausible that a documented recent population bottleneck could have heightened the susceptibility of these macaques to PFEH. Further research on living primate populations is needed to better understand the causes of PFEH in wild primates and to evaluate whether such features can be used to assess the impact of human-related disturbance.
Opening a can of worms: a test of the coinfection facilitation hypothesis
Authors: Rodgers Maria L. , Bolnick Daniel I. 
Published: May 2023

ABSTRACTParasitic infections are a global occurrence and impact the health of many species. Coinfections, where two or more species of parasite are present in a host, are a common phenomenon across species. Coinfecting parasites can interact directly, or indirectly via their manipulation of (and susceptibility to) the immune system of their shared host. Helminths, such as the cestodeSchistocephalus solidus, are well known to suppress immunity of their host (threespine stickleback,Gasterosteus aculeatus), potentially facilitating other parasite species. Yet, hosts can evolve a more robust immune response (as seen in some stickleback populations), potentially turning facilitation into inhibition. Using wild-caught stickleback from 21 populations with non-zeroS. solidusprevalence, we tested ana priorihypothesis thatS. solidusinfection facilitates infection by other parasites. Consistent with this hypothesis, individuals withS. solidusinfections have 18.6% higher richness of other parasites, compared toS. solidus-uninfected individuals from the same lakes. This facilitation-like trend is stronger in lakes whereS. solidusis particularly successful but is reversed in lakes with sparse and smaller cestodes (indicative of stronger host immunity). These results suggest that a geographic mosaic of host-parasite coevolution might lead to a mosaic of between-parasite facilitation/inhibition effects.
Reconstructing cell type evolution across species through cell phylogenies of single-cell RNAseq data
Authors: Mah Jasmine L. , Dunn Casey W. 
Published: May 2023

AbstractThe origin and evolution of cell types has emerged as a key topic in evolutionary biology. Driven by rapidly accumulating single-cell datasets, recent attempts to infer cell type evolution have largely been limited to pairwise comparisons because we lack approaches to build cell phylogenies using model-based approaches. Here we approach the challenges of applying explicit phylogenetic methods to single-cell data by using principal components as phylogenetic characters. We infer a cell phylogeny from a large, comparative single-cell data set of eye cells from five distantly-related mammals. Robust cell type clades enable us to provide a phylogenetic, rather than phenetic, definition of cell type, allowing us to forgo marker genes and phylogenetically classify cells by topology. We further observe evolutionary relationships between diverse vessel endothelia and identify the myelinating and non-myelinating Schwann cells as sister cell types. Finally, we examine principal component loadings and describe the gene expression dynamics underlying the function and identity of cell type clades that have been conserved across the five species. A cell phylogeny provides a rigorous framework towards investigating the evolutionary history of cells and will be critical to interpret comparative single-cell datasets that aim to ask fundamental evolutionary questions.
GGAssembler: precise and economical design and synthesis of combinatorial mutation libraries
Authors: Hoch Shlomo Yakir , Netzer Ravit , Weinstein Jonathan Yaacov , Krauss Lucas , Hakeny Karen , Fleishman Sarel Jacob 
Published: May 2023

AbstractGolden Gate assembly (GGA) can seamlessly generate full-length genes from DNA fragments. In principle, GGA could be used to design combinatorial mutation libraries for protein engineering, but creating accurate, complex, and cost-effective libraries has been challenging. We present GGAssembler, a graph-theoretical method for economical design of DNA fragments that assemble a combinatorial library that encodes any desired diversity. We used GGAssembler for one-potin vitroassembly of camelid antibody libraries comprising >105variants with DNA costs <0.007$ per variant and dropping significantly with increased library complexity. >93% of the desired variants were present in the assembly product and >99% were represented within the expected order of magnitude as verified by deep sequencing. The GGAssembler workflow is, therefore, an accurate approach for generating complex variant libraries that may drastically reduce costs and accelerate discovery and optimization of antibodies, enzymes and other proteins. The workflow is accessible through a web interface athttps://github.com/Fleishman-Lab/GGAssembler/blob/master/example/colab_oligos_design.ipynb.
Benefit versus Risk of Endomyocardial Biopsy for Heart Transplant Patients in the Contemporary Era
Authors: Cusi Vincenzo , Vaida Florin , Wettersten Nicholas , Rodgers Nicholas , Tada Yuko , Gerding Bryn , Greenberg Barry , Urey Marcus Anthony , Adler Eric , Kim Paul J. 
Published: May 2023

AbstractBackgroundThe reference standard of detecting acute rejection (AR) in adult heart transplant (HTx) patients is an endomyocardial biopsy (EMB). The majority of EMBs are performed in asymptomatic patients. However, the benefit of diagnosing and treating AR compared to the risk of EMB complications has not been compared in the contemporary era (2010-current).MethodsThe authors retrospectively analyzed 2,769 EMB obtained in 326 consecutive HTx patients between August 2019 and August 2022. Variables included surveillance versus for cause indication, recipient and donor characteristics, EMB procedural data and pathologic grades, treatment for AR, and clinical outcomes.ResultsThe overall EMB complication rate was 1.6%. EMBs performed within 1 month after HTx compared to after 1 month from HTx showed significantly increased complications (OR = 12.74, p < 0.001). The treated AR rate was 14.2% in the for cause EMBs and 1.2% in the surveillance EMBs. We found the benefit/risk ratio was significantly lower in the surveillance compared to the for cause EMB group (OR = 0.05, p < 0.001). We also found the benefit to be lower than risk in surveillance EMBs.ConclusionsThe yield of surveillance EMBs has declined, while for cause EMBs continued to demonstrate a high benefit/risk ratio. The risk of EMB complications was highest within 1 month after HTx. Surveillance EMB protocols in the contemporary era may need to be re-evaluated.
libSBOLj3: A graph-based library for design and data exchange in synthetic biology
Authors: Mısırlı Göksel 
Published: May 2023

AbstractThe Synthetic Biology Open Language version 3 data standard provides a graph-based approach to exchange information about biological designs. The new data model has major updates and offers several features for software tools. Here, we present libSBOLj3 to facilitate data exchange and provide interoperability between computer-aided design and automation tools using this standard. The library adopts a graph-based approach. Tool developers can extend these graphs with application-specific information and use detailed validation reports to identify errors and interoperability issues and apply best practice rules. The libSBOLj3 library is implemented in Java and can be downloaded or used as a Maven dependency. The open-source project, examples and documentation about accessing and using the library are available via GitHub athttps://github.com/SynBioDex/libSBOLj3.
CaliAli, a tool for long-term tracking of neuronal population dynamics in calcium imaging
Authors: Vergara Pablo , Wang Yuteng , Srinivasan Sakthivel , Cherasse Yoan , Naoi Toshie , Sugaya Yuki , Sakurai Takeshi , Kano Masanobu , Sakaguchi Masanori 
Published: May 2023

AbstractNeuron-tracking algorithms exhibit suboptimal performance in calcium imaging when the same neurons are not consistently detected, as unmatched features hinder intersession alignment. CaliAli addresses this issue by employing an alignment-before-extraction strategy that incorporates vasculature information to improve the detectability of weak signals and maximize the number of trackable neurons. By excelling in neural remapping and high spatial overlap scenarios, CaliAli paves the way toward further understanding long-term neural network dynamics.
VirB, a transcriptional activator of virulence inShigella flexneri, uses CTP as a cofactor
Authors: Antar Hammam , Gruber Stephan 
Published: May 2023

AbstractVirB is a transcriptional activator of virulence in the gram-negative bacteriumShigella flexneri. It is encoded by the large invasion plasmid, pINV, and is thought to counteract the transcriptional silencing mediated by the nucleoid structuring protein, H-NS. Mutations invirBlead to loss of virulence. Studies suggest that VirB binds to specific DNA sequences, remodels the H-NS nucleoprotein complexes, and changes DNA supercoiling. VirB belongs to the superfamily of ParB proteins which are involved in plasmid and chromosome partitioning often as part of a ParABS system. Like ParB, VirB forms discrete foci inShigella flexnericells harbouring pINV. Our results reveal that purified preparations of VirB specifically bind the ribonucleotide CTP. We show that VirB slowly but detectably hydrolyses CTP, which is mildly stimulated by thevirStargeting sequences found on pINV. CTP and DNA binding promote VirB clamp closure. Curiously, DNA stimulation of clamp closure appears efficient even withoutvirSsequences. These findings suggest that VirB acts as a CTP-dependent DNA clamp and may indicate that so far elusive factors might prevent offsite DNA clampingin vivo.
Importin 13-dependent Axon Diameter Growth Regulates Conduction Speeds along Myelinated CNS Axons
Authors: Bin Jenea M , Suminaite Daumante , Benito-Kwiecinski Silvia K. , Kegel Linde , Rubio-Brotons Maria , Early Jason J , Soong Daniel , Livesey Matthew R , Poole Richard J , Lyons David A 
Published: May 2023

SummaryCentral nervous system neurons have axons that vary over 100-fold in diameter. This diversity contributes to the regulation of myelination and conduction velocity along axons, which is critical for proper nervous system function. Despite this importance, technical challenges have limited our understanding of mechanisms controlling axon diameter growth, preventing systematic dissection of how manipulating diameter affects conduction along individual axons. Here, we establish zebrafish as system to investigate the regulation of axon diameter and axonal conductionin vivo. We identify a role for importin 13b specifically in axon diameter growth, that is independent of axonal length and overall cell size. Impairment of diameter growth along individual myelinated axons reduced conduction velocity in proportion to the diameter, but had no effect on the precision of action potential propagation or ability to fire at high frequencies. This work highlights an axon diameter-specific mechanism of growth that regulates conduction speeds along myelinated axons.
DNA methylation-environment interactions in the human genome
Authors: Johnston Rachel A. , Aracena Katherine A. , Barreiro Luis B. , Lea Amanda J. , Tung Jenny 
Published: May 2023

AbstractPreviously we showed that a massively parallel reporter assay, mSTARR-seq, could be used to simultaneously test for both enhancer-like activity and DNA methylation-dependent enhancer activity for millions of loci in a single experiment (Leaet al., 2018). Here we apply mSTARR-seq to query nearly the entire human genome, including almost all CpG sites profiled either on the commonly used Illumina Infinium MethylationEPIC array or via reduced representation bisulfite sequencing. We show that fragments containing these sites are enriched for regulatory capacity, and that methylation-dependent regulatory activity is in turn sensitive to the cellular environment. In particular, regulatory responses to interferon alpha (IFNA) stimulation are strongly attenuated by methyl marks, indicating widespread DNA methylation-environment interactions. In agreement, methylation-dependent responses to IFNA identified via mSTARR-seq predict methylation-dependent transcriptional responses to challenge with influenza virus in human macrophages. Our observations support the idea that pre-existing DNA methylation patterns can influence the response to subsequent environmental exposures—one of the tenets of biological embedding. However, we also find that, on average, sites previously associated with early life adversity are not more likely to functionally influence gene regulation than expected by chance.
Genomic and metabolic plasticity drive alternative scenarios for adaptingPseudomonas putidato non-native substrate D-xylose
Authors: Dvořák Pavel , Burýšková Barbora , Popelářová Barbora , Ebert Birgitta , Botka Tibor , Bujdoš Dalimil , Sánchez-Pascuala Alberto , Schöttler Hannah , Hayen Heiko , Lorenzo Víctor de , Blank Lars M. , Benešík Martin 
Published: May 2023

AbstractD-Xylose, a major constituent of plant biomass and second most abundant sugar on Earth, holds a considerable potential as a substrate for sustainable bio-production. Pseudomonas putida KT2440 is an attractive bacterial host for valorizing biogenic feedstocks but lacks a xylose utilization pathway. While several attempts to engineer P. putida for growth on xylose have been reported, a comprehensive understanding of xylose metabolism in this bacterium is lacking, hindering its further improvement and rational tailoring for specific biotechnological purposes. In this study, we elucidated the xylose metabolism in the genome-reduced P. putida strain, EM42, endowed with xylose isomerase pathway (xylAB) and transporter (xylE) from Escherichia coli and used the obtained knowledge in combination with adaptive laboratory evolution to accelerate the bacterium’s growth on the pentose sugar. Carbon flux analyses, targeted gene knock-outs, and in vitro enzyme assays portrayed xylose assimilation in P. putida and confirmed a partially cyclic upper xylose metabolism. Deletion of the local transcriptional regulator gene hexR de-repressed genes of several key catabolic enzymes and reduced the lag phase on xylose. Guided by metabolic modeling, we augmented P. putida with additional heterologous pentose phosphate pathway genes and subjected rationally prepared strains to adaptive laboratory evolution (ALE) on xylose. The descendants showed accelerated growth and reduced growth lag. Genomic and proteomic analysis of engineered and evolved mutants revealed the importance of a large genomic re-arrangement, transaldolase overexpression, and balancing gene expression in the synthetic xylABE operon. Importantly, omics analyses found that similar growth characteristics of two superior mutants were achieved through distinct evolutionary paths. This work provides a unique insight into how cell metabolism adjusts to a non-native substrate; it highlights the remarkable genomic and metabolic plasticity of P. putida and demonstrates the power of combining knowledge-driven engineering with ALE in generating desirable microbial phenotypes.HighlightsElucidated xylose catabolism via exogenous isomerase pathway inP. putidaEM42.Deletion of transcriptional regulator HexR improved growth on xylose.Knowledge-guided interventions and adaptive evolution accelerated growth.Omics analyses of selected mutants highlighted the genomic and metabolic plasticity ofP. putida.Two mutants with superior characteristics emerged from distinct evolutionary paths.
Retinoblastoma protein activity revealed by CRISPRi study of divergent Rbf1 and Rbf2 paralogs
Authors: Raicu Ana-Maria , Castanheira Patricia , Arnosti David N. 
Published: May 2023

ABSTRACTRetinoblastoma tumor suppressor proteins regulate the key transition from G1 to S phase of the cell cycle. The mammalian Rb family comprises Rb, p107, and p130, with overlapping and unique roles in gene regulation. Drosophila experienced an independent gene duplication event, leading to the Rbf1 and Rbf2 paralogs. To uncover the significance of paralogy in the Rb family, we used CRISPRi. We engineered dCas9 fusions to Rbf1 and Rbf2, and deployed them to gene promoters in developing Drosophila tissue to study their relative impacts on gene expression. On some genes, both Rbf1 and Rbf2 mediate potent repression, in a highly distance-dependent manner. In other cases, the two proteins have different effects on phenotype and gene expression, indicating different functional potential. In a direct comparison of Rb activity on endogenous genes and transiently transfected reporters, we found that only qualitative, but not key quantitative aspects of repression were conserved, indicating that the native chromatin environment generates context-specific effects of Rb activity. Our study uncovers the complexity of Rb-mediated transcriptional regulation in a living organism, which is clearly impacted by the different promoter landscapes and the evolution of the Rb proteins themselves.