bluuebunny/crossref_metadata_2025_split huggingface dataset:
JUMP Cell Painting dataset: morphological impact of 136,000 chemical and genetic perturbations
Authors: Chandrasekaran Srinivas Niranj , Ackerman Jeanelle , Alix Eric , Ando D. Michael , Arevalo John , Bennion Melissa , Boisseau Nicolas , Borowa Adriana , Boyd Justin D. , Brino Laurent , Byrne Patrick J. , Ceulemans Hugo , Ch’ng Carolyn , Cimini Beth A. , Clevert Djork-Arne , Deflaux Nicole , Doench John G , Dorval Thierry , Doyonnas Regis , Dragone Vincenza , Engkvist Ola , Faloon Patrick W. , Fritchman Briana , Fuchs Florian , Garg Sakshi , Gilbert Tamara J. , Glazer David , Gnutt David , Goodale Amy , Grignard Jeremy , Guenther Judith , Han Yu , Hanifehlou Zahra , Hariharan Santosh , Hernandez Desiree , Horman Shane R , Hormel Gisela , Huntley Michael , Icke Ilknur , Iida Makiyo , Jacob Christina B. , Jaensch Steffen , Khetan Jawahar , Kost-Alimova Maria , Krawiec Tomasz , Kuhn Daniel , Lardeau Charles-Hugues , Lembke Amanda , Lin Francis , Little Kevin D. , Lofstrom Kenneth R. , Lotfi Sofia , Logan David J. , Luo Yi , Madoux Franck , Marin Zapata Paula A. , Marion Brittany A. , Martin Glynn , McCarthy Nicola Jane , Mervin Lewis , Miller Lisa , Mohamed Haseeb , Monteverde Tiziana , Mouchet Elizabeth , Nicke Barbara , Ogier Arnaud , Ong Anne-Laure , Osterland Marc , Otrocka Magdalena , Peeters Pieter J. , Pilling James , Prechtl Stefan , Qian Chen , Rataj Krzysztof , Root David E , Sakata Sylvie K. , Scrace Simon , Shimizu Hajime , Simon David , Sommer Peter , Spruiell Craig , Sumia Iffat , Swalley Susanne E , Terauchi Hiroki , Thibaudeau Amandine , Unruh Amy , Van de Waeter Jelle , Van Dyck Michiel , van Staden Carlo , Warchoł Michał , Weisbart Erin , Weiss Amélie , Wiest-Daessle Nicolas , Williams Guy , Yu Shan , Zapiec Bolek , Żyła Marek , Singh Shantanu , Carpenter Anne E. 
Published: March 2023

AbstractImage-based profiling has emerged as a powerful technology for various steps in basic biological and pharmaceutical discovery, but the community has lacked a large, public reference set of data from chemical and genetic perturbations. Here we present data generated by the Joint Undertaking for Morphological Profiling (JUMP)-Cell Painting Consortium, a collaboration between 10 pharmaceutical companies, six supporting technology companies, and two non-profit partners. When completed, the dataset will contain images and profiles from the Cell Painting assay for over 116,750 unique compounds, over-expression of 12,602 genes, and knockout of 7,975 genes using CRISPR-Cas9, all in human osteosarcoma cells (U2OS). The dataset is estimated to be 115 TB in size and capturing 1.6 billion cells and their single-cell profiles. File quality control and upload is underway and will be completed over the coming months at the Cell Painting Gallery:https://registry.opendata.aws/cellpainting-gallery. A portal to visualize a subset of the data is available athttps://phenaid.ardigen.com/jumpcpexplorer/.
Three Species of Axenic Mosquito Larvae Recruit a Shared Core of Bacteria in a Common Garden Experiment
Authors: Hyde Josephine , Brackney Doug E , Steven Blaire 
Published: March 2023

ABSTRACTIn this study we describe the generation of two new species of axenic mosquito,Aedes albopictusandAedes triseriatus.Along withAedes aegypti, axenic larvae of these three species were exposed to an environmental water source to document the assembly of the microbiome in a common garden experiment. Additionally, the larvae were reared either individually or combinatorially with the other species to characterize the effects of co-rearing on the composition of the microbiome. We found that the microbiome of the larvae was composed of a relatively low diversity collection of bacteria from the colonizing water. The abundance of bacteria in the water was a poor predictor for their abundance in the larvae, suggesting the larval microbiome is made up of a subset of relatively rare aquatic bacteria. We found eleven bacterial 16S rRNA gene amplicon sequence variants (ASVs) that were conserved amongst>90% of the mosquitoes sampled, including two found in 100% of the larvae, pointing to a conserved core of bacteria capable of colonizing all three species of mosquito. Yet, the abundance of these ASVs varied widely between larvae suggesting individuals harbored largely unique microbiome structures, even if they overlapped in membership. Finally, larvae reared in a tripartite mix of the host species consistently showed a convergence in the structure of their microbiome, indicating that multi-species interactions between hosts potentially lead to shifts in the composition of their respective microbiomes.IMPORTANCEThis study is the first report of the axenic (free of external microbes) rearing of two species of mosquito,Aedes albopictusandAedes triseriatus. With our previous report of axenicAedes aegypti, brings the number of axenic species to three. We designed a method to perform a common garden experiment to characterize the bacteria the three species of axenic larvae assemble from their surroundings. Furthermore, species could be reared in isolation or in multi-species combinations to assess how host species interactions influence the composition of the microbiome. We found all three species recruited a common core of bacteria from their rearing water, with a large contingent of rare and sporadically detected bacteria. Finally, we also show that co-rearing of mosquito larvae leads to a coalescence in the composition of their microbiome, indicating that host species interactions potentially influence the composition of the microbiome.
Seventy Years of Mortality Transition in India: 1950-2021
Authors: Chaurasia Aalok Ranjan 
Published: March 2023

AbstractMortality in India remains high by international standards. This paper analyses mortality transition in India during the 70 years since 1950 based on the annual estimates of age-specific probabilities of death prepared by the United Nations Population Division for the period 1950-2021. The analysis reveals that characterisation of mortality transition is sensitive to the summary index of mortality used. Mortality transition in India based on the geometric mean of the age-specific probabilities of death is found to be different from that based on the life expectancy at birth. The transition in mortality based on the geometric mean of age-specific probabilities of death accelerated during 2008-2019 but decelerated when based on the life expectancy at birth. The reason is that mortality transition in younger ages has been faster than mortality transition in older ages. The analysis also reveals that there were around 4.3 excess deaths associated with the COVID-19 epidemic in the country leading to a loss of around 3.7 years in the life expectancy at birth between 2019 and 2021.
High-resolution functional description of vaginal microbiomes in health and disease
Authors: Holm Johanna B. , France Michael T. , Gajer Pawel , Ma Bing , Brotman Rebecca M. , Shardell Michelle , Forney Larry , Ravel Jacques 
Published: March 2023

ABSTRACTBackgroundALactobacillus-dominated vaginal microbiome provides the first line of defense against numerous adverse genital tract health outcomes. However, there is limited understanding of the mechanisms by which the vaginal microbiome modulates protection, as prior work mostly described its composition through morphologic assessment and marker gene sequencing methods that do not capture functional information. To address this limitation, we developed metagenomic community state types (mgCSTs) which uses metagenomic sequences to describe and define vaginal microbiomes based on both composition and function.ResultsMgCSTs are categories of microbiomes classified using taxonomy and the functional potential encoded in their metagenomes. MgCSTs reflect unique combinations of metagenomic subspecies (mgSs), which are assemblages of bacterial strains of the same species, within a microbiome. We demonstrate that mgCSTs are associated with demographics such as age and race, as well as vaginal pH and Gram stain assessment of vaginal smears. Importantly, these associations varied between mgCSTs predominated by the same bacterial species. A subset of mgCSTs, including three of the six predominated byGardnerellamgSs, as well as a mgSs ofL. iners, were associated with a greater likelihood of Amsel bacterial vaginosis diagnosis. ThisL. inersmgSs, among other functional features, encoded enhanced genetic capabilities for epithelial cell attachment that could facilitate cytotoxin-mediated cell lysis. Finally, we report a mgSs and mgCST classifier as an easily applied, standardized method for use by the microbiome research community.ConclusionsMgCSTs are a novel and easily implemented approach to reducing the dimension of complex metagenomic datasets, while maintaining their functional uniqueness. MgCSTs enable investigation of multiple strains of the same species and the functional diversity in that species. Future investigations of functional diversity may be key to unraveling the pathways by which the vaginal microbiome modulates protection to the genital tract. Importantly, our findings support the hypothesis that functional differences between vaginal microbiomes, including those that may look compositionally similar, are critical considerations in vaginal health. Ultimately, mgCSTs may lead to novel hypotheses concerning the role of the vaginal microbiome in promoting health and disease, and identify targets for novel prognostic, diagnostic, and therapeutic strategies to improve women’s genital health.
Natural mutations of humanXDHpromote the nitrite (NO2-)-reductase capacity of xanthine oxidoreductase: a novel mechanism to promote redox health?
Authors: Massimo G. , Khambata R. S. , Chapman T. , Birchall K. , Shabbir A. , Dyson Nicki , Rathod K. , Borghi C. , Ahluwalia A. 
Published: March 2023

AbstractSeveral rare genetic variations of humanXDHhave been shown to alter xanthine oxidoreductase (XOR) activity leading to impaired purine catabolism. However, XOR is a multi-functional enzyme that depending upon the environmental conditions also expresses oxidase activity leading to both O·-and H O and nitrite (·NO-) reductase activity leading to NO. Since these products express important, and often diametrically opposite, biological activity consideration of the impact of XOR mutations in the context of each aspect of the biochemical activity of the enzyme is needed to determine the potential full impact of these variants. Herein, we show that known naturally occurringhXDHmutations do not have a uniform impact upon the biochemical activity of the enzyme in terms of uric acid (UA), reactive oxygen species (ROS) and nitric oxide (·NO) formation. We show that the His1221Arg mutant, in the presence of xanthine, increases UA, O2·-and NO generation compared to the WT, whilst the Ile703Val increases UA and ·NO formation, but not O2·-. We speculate that this change in the balance of activity of the enzyme is likely to endow those carrying these mutations with a harmful or protective influence over health that may explain the current equipoise underlying the perceived importance ofXDHmutations. We also suggest that targeting enzyme activity to enhance the NO2--reductase profile in those carrying such mutations may provide novel therapeutic options, particularly in cardiovascular disease.HighlightsMutations of xanthine oxidoreductase modulate both its expression and activityThe His1221Arg natural mutation increases xanthine oxidoreductase activityRaised xanthine oxidoreductase activity coupled with increased availability of nitrite substrate leads to increased NO provision
Mathematical models disentangle the role of IL-10 feedbacks in human monocytes upon proinflammatory activation
Authors: Nikaein Niloofar , Tuerxun Kedeye , Cedersund Gunnar , Eklund Daniel , Kruse Robert , Särndahl Eva , Nånberg Eewa , Thonig Antje , Repsilber Dirk , Persson Alexander , Nyman Elin 
Published: March 2023

AbstractInflammation is one of the vital mechanisms through which the immune system responds to harmful stimuli. During inflammation, pro and anti-inflammatory cytokines interplay to orchestrate fine-tuned, dynamic immune responses. The cytokine interplay governs switches in the inflammatory response and dictates the propagation of inflammation. Molecular pathways underlying the interplay are complex, and time-resolved monitoring of mediators and cytokines is necessary as a basis to study them in detail. Our understanding can be advanced byin silicomodels which enable to analyze the system of interactions and their dynamical interplay in detail. We, therefore, used a mathematical modeling approach to study the interplay between prominent pro and anti-inflammatory cytokines with a focus on Tumor Necrosis Factor (TNF) and Interleukin 10 (IL-10) in lipopolysaccharide (LPS)-primed primary human monocytes. Relevant time-resolved data were generated by experimentally adding or blocking IL-10 at different time points. The model was successfully trained and could predict independent validation data and was further used to performin silicoexperiments to disentangle the role of IL-10 feedbacks in acute inflammation. We used the insight to obtain a reduced predictive model including only the necessary IL-10-mediated feedbacks. Finally, the validated reduced model was used to predict early IL-10 – TNF switches in the inflammatory response. Overall, we gained detailed insights into fine-tuning of inflammatory responses in human monocytes and present a model for further use in studying the complex and dynamic process of cytokine-regulated acute inflammation.
Di-berberine conjugates as chemical probes ofPseudomonas aeruginosaMexXY-OprM efflux function and inhibition
Authors: Kavanaugh Logan G. , Mahoney Andrew R. , Dey Debayan , Wuest William M. , Conn Graeme L. 
Published: March 2023

AbstractThe Resistance-Nodulation-Division (RND) efflux pump superfamily is pervasive among Gram-negative pathogens and contributes extensively to clinical antibiotic resistance. The opportunistic pathogenPseudomonas aeruginosacontains 12 RND-type efflux systems, with four contributing to resistance including MexXY-OprM which is uniquely able to export aminoglycosides. At the site of initial substrate recognition, small molecule probes of the inner membrane transporter (e.g., MexY) have potential as important functional tools to understand substrate selectivity and a foundation for developing adjuvant efflux pump inhibitors (EPIs). Here, we optimized the scaffold of berberine, a known but weak MexY EPI, using anin-silicohigh-throughput screen to identify di-berberine conjugates with enhanced synergistic action with aminoglycosides. Further, docking and molecular dynamics simulations of di-berberine conjugates reveal unique contact residues and thus sensitivities of MexY from distinctP. aeruginosastrains. This work thereby reveals di-berberine conjugates to be useful probes of MexY transporter function and potential leads for EPI development.
split-intein Gal4 provides intersectional genetic labeling that is fully repressible by Gal80
Authors: Ewen-Campen Ben , Luan Haojiang , Xu Jun , Singh Rohit , Joshi Neha , Thakkar Tanuj , Berger Bonnie , White Benjamin H. , Perrimon Norbert 
Published: March 2023

AbstractThe split-Gal4 system allows for intersectional genetic labeling of highly specific cell-types and tissues inDrosophila. However, the existing split-Gal4 system, unlike the standard Gal4 system, cannot be repressed by Gal80, and therefore cannot be controlled temporally. This lack of temporal control precludes split-Gal4 experiments in which a genetic manipulation must be restricted to specific timepoints. Here, we describe a new split-Gal4 system based on a self-excising split-intein, which drives transgene expression as strongly as the current split-Gal4 system and Gal4 reagents, yet which is fully repressible by Gal80. We demonstrate the potent inducibility of “split-intein Gal4”in vivousing both fluorescent reporters and via reversible tumor induction in the gut. Further, we show that our split-intein Gal4 can be extended to the drug-inducible GeneSwitch system, providing an independent method for intersectional labeling with inducible control. We also show that the split-intein Gal4 system can be used to generate highly cell-type specific genetic drivers based onin silicopredictions generated by single cell RNAseq (scRNAseq) datasets, and we describe a new algorithm (“Two Against Background” or TAB) to predict cluster-specific gene pairs across multiple tissue-specific scRNA datasets. We provide a plasmid toolkit to efficiently create split-intein Gal4 drivers based on either CRISPR knock-ins to target genes or using enhancer fragments. Altogether, the split-intein Gal4 system allows for the creation of highly specific intersectional genetic drivers that are inducible/repressible.Significance statementThe split-Gal4 system allowsDrosophilaresearchers to drive transgene expression with extraordinary cell type specificity. However, the existing split-Gal4 system cannot be controlled temporally, and therefore cannot be applied to many important areas of research. Here, we present a new split-Gal4 system based on a self-excising split-intein, which is fully controllable by Gal80, as well as a related drug-inducible split GeneSwitch system. This approach can both leverage and inform single-cell RNAseq datasets, and we introduce an algorithm to identify pairs of genes that precisely and narrowly mark a desired cell cluster. Our split-intein Gal4 system will be of value to theDrosophilaresearch community, and allow for the creation of highly specific genetic drivers that are also inducible/repressible.
Microbiomes of blood feeding triatomines in the context of their predatory relatives and the environment
Authors: Tarabai Hassan , Floriano Anna Maria , Zima Jan , Filová Natalia , Brown Joel J. , Roachell Walter , Smith Robert L. , Beatty Norman L. , Vogel Kevin J. , Nováková Eva 
Published: March 2023

AbstractThe importance of gut microbiomes has become generally recognized in vector biology. This study addresses microbiome signatures in North AmericanTriatomaspecies of public health significance (vectors ofTrypanosoma cruzi) linked to their blood feeding strategy and the natural habitat. To place theTriatomaassociated microbiomes within a complex evolutionary and ecological context, we sampled sympatricTriatomapopulations, related predatory reduviids, unrelated ticks, and environmental material from vertebrate nests where these arthropods reside. Along with fiveTriatomaspecies, we have characterized microbiomes of five reduviids (Stenolemoides arizonensis,Ploiaria hirticornis,Zelus longipes, and twoReduviusspecies), a single soft tick species,Ornithodoros turicata,and environmental microbiomes from selected sites in Arizona, Texas, Florida and Georgia. The microbiomes of predatory reduviids lack a shared core microbiota. Like in triatomines, microbiome dissimilarities among species corelate with dominance of a single bacterial taxa. These includeRickettsia,Lactobacillus, CandidatusMidichloria, andZymobacter, which are often accompanied by known symbiotic genera, i.e.,Wolbachia,CandidatusLariskella,Asaia,Gilliamella, andBurkholderia.We have further identified compositional convergence of analyzed microbiomes in respect to the host phylogenetic distance in both blood feeding and predatory reduviids. While microbiomes of two reduviid species from Emesinae family reflect their close relationship, the microbiomes of allTriatomaspecies repeatedly form a distinct monophyletic cluster highlighting their phylosymbiosis. Furthermore, based on environmental microbiome profiles and blood meal analysis, we propose three epidemiologically relevant and mutually interrelated bacterial sources forTriatomamicrobiomes, i.e., host abiotic environment, host skin microbiome, and pathogens circulating in host blood.ImportanceThis study places microbiomes of blood feeding North AmericanTriatomavectors (Reduviidae) into a broader evolutionary and ecological context provided by related predatory assassin bugs (Reduviidae), another unrelated vector species (soft tickOrnithodor turicata), and the environment these arthropods cohabit. For both vectors, microbiome analyses suggest three interrelated sources of bacteria, i.e., microbiome of vertebrate nests as their natural habitat, vertebrate skin microbiome, and pathobiome circulating in vertebrate blood. Despite an apparent influx of environment-associated bacteria into the arthropod microbiomes,Triatomamicrobiomes retain their specificity, forming a distinct cluster that significantly differ from both predatory relatives and ecologically comparable ticks. Similarly, within the related predatory Reduviidae, we found the host phylogenetic distance to underlie microbiome similarities.
Efficient Visual Heuristics in the Perception of Physical Object Properties
Authors: Paulun Vivian C. , Bayer Florian S. , Tenenbaum Joshua B. , Fleming Roland W. 
Published: March 2023

AbstractVision is more than object recognition: In order to interact with the physical world, we estimate object properties such as mass, fragility, or elasticity by sight. The computational basis of this ability is poorly understood. Here, we propose a model based on the statistical appearance of objects, i.e., how they typically move, flow, or fold. We test this idea using a particularly challenging example: estimating the elasticity of bouncing objects. Their complex movements depend on many factors, e.g., elasticity, initial speed, and direction, and thus every object can produce an infinite number of different trajectories. By simulating and analyzing the trajectories of 100k bouncing cubes, we identified and evaluated 23 motion features that could individually or in combination be used to estimate elasticity. Experimentally teasing apart these competing but highly correlated hypotheses, we found that humans represent bouncing objects in terms of several different motion features but rely on just a single one when asked to estimate elasticity. Which feature this is, is determined by the stimulus itself: Humans rely on the duration of motion if the complete trajectory is visible, but on the maximal bounce height if the motion duration is artificially cut short. Our results suggest that observers take into account the computational costs when asked to judge elasticity and thus rely on a robust and efficient heuristic. Our study provides evidence for how such a heuristic can be derived—in an unsupervised manner—from observing the natural variations in many exemplars.Significance StatementHow do we perceive the physical properties of objects? Our findings suggest that when tasked with reporting the elasticity of bouncing cubes, observers rely on simple heuristics. Although there are many potential visual cues, surprisingly, humans tend to switch between just a handful of them depending on the characteristics of the stimulus. The heuristics predict not only the broad successes of human elasticity perception but also the striking pattern of errors observers make when we decouple the cues from ground truth. Using a big data approach, we show how the brain could derive such heuristics by observation alone. The findings are likely an example of ‘computational rationality’, in which the brain trades off task demands and relative computational costs.