bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biosynthesis of the Multifunctional Isopropylstilbene inPhotorhabdus laumondiiInvolves Cross-Talk between Specialized and Primary Metabolism
Authors: Kavakli Siyar , Grammbitter Gina L. C. , Bode Helge B. 
Published: October 2022

AbstractIsopropylstilbene (IPS) derived from the entomopathogenic bacteriumPhotorhabdusrepresents the only known stilbene which is not produced by a plant stilbene synthase but a bacterial PKS II synthase. While the exclusive cyclization reaction, responsible for the formation of the characteristic iso-branched side-chain of the molecule, was studied in the past, some parts of the biosynthetic route remained elusive. In this study, we revealed the role of StlB that is able to produce CoA-derivatives and demonstrated the elongation of cinnamoyl-CoA with enzymes from the bacterial fatty acid biosynthesis pathway. Thus, we deciphered cross-talk between the enzymes from primary and specialized metabolism. These insights led, for the first time, to the production of IPS in a heterologous host.
Categorising update mechanisms for graph-structured metapopulations
Authors: Yagoobi Sedigheh , Sharma Nikhil , Traulsen Arne 
Published: October 2022

AbstractThe structure of a population strongly influences its evolutionary dynamics. In various settings ranging from biology to social systems, individuals tend to interact more often with those present in their proximity and rarely with those far away. A common approach to model the structure of a population is Evolutionary Graph Theory. In this framework, each graph node is occupied by a reproducing individual. The links connect these individuals to their neighbours. The offspring can be placed on neighbouring nodes, replacing the neighbours – or the progeny of its neighbours can replace a node during the course of ongoing evolutionary dynamics. Extending this theory by replacing single individuals with subpopulations at nodes yields a graph-structured metapopulation. The dynamics between the different local subpopulations is set by an update mechanism. There are many such update mechanisms. Here, we classify update mechanisms for structured metapopulations, which allows to find commonalities between past work and illustrate directions for further research and current gaps of investigation.
Carboxylic acids that drive mosquito attraction to humans activate Ionotropic Receptors
Authors: Ray Garrett , Huff Robert M. , Castillo John S. , Bellantuono Anthony J. , DeGennaro Matthew , Pitts R. Jason 
Published: October 2022

AbstractFemale mosquitoes are attracted to sources of blood by responding to odor plumes that are emitted by their preferred hosts. Acidic volatile compounds, including carboxylic acids, represent particularly salient odors driving this attraction. Importantly, carboxylic acids are major constituents of human sweat and volatiles generated by skin microbes. As such, they are likely to impact human host preference, which is a dominant factor in disease transmission cycles. A more complete understanding of mosquito host attraction will necessitate the elucidation of molecular mechanisms of volatile odor detection that function in peripheral sensory neurons. Recent studies have shown that members of the variant ionotropic glutamate receptor gene family are necessary for physiological and behavioral responses to acidic volatiles inAedes. In this study, we have identified a subfamily of variant ionotropic receptors that share sequence homology across several important vector species and are likely to be activated by carboxylic acids. Moreover, we demonstrate that selected members of this subfamily are activated by short chain carboxylic acids in a heterologous cell expression system. Our results are consistent with the hypothesis that members of this receptor class underlie acidic volatile sensitivity in vector mosquitoes and provide a frame of reference for future development of novel mosquito attractant and repellent technologies.
PMI estimation through metabolomics and potassium analysis on animal vitreous humour
Authors: Locci Emanuela , Stocchero Matteo , Gottardo Rossella , Chighine Alberto , De-Giorgio Fabio , Ferino Giulio , Nioi Matteo , Demontis Roberto , Tagliaro Franco , d’Aloja Ernesto 
Published: October 2022

AbstractIntroductionThe estimation of post-mortem interval remains a major challenge in forensic science. Most of the proposed approaches lack the reliability required to meet the rigorous forensic standards.ObjectivesWe applied1H NMR metabolomics to estimate PMI on ovine vitreous humour comparing the results with the actual scientific gold standard, namely vitreous potassium concentrations.MethodsVitreous humour samples were collected in a time frame ranging from 6 to 86 hours after death. Experiments were performed by using1H NMR metabolomics and Ion Capillary Analysis. Data were submitted to multivariate statistical data analysis.ResultsA multivariate calibration model was built to estimate PMI based on 47 vitreous humour samples. The model was validated with an independent test set of 24 samples, obtaining a prediction error on the entire range of 6.9 h for PMI<24h, 7.4 h for PMI between 24 and 48h, and 10.3 h for PMI>48 h. Time-related modifications of the1H NMR vitreous metabolomic profile could predict PMI better than potassium up to 48 hours after death, while a combination of the two is better than the single approach for higher PMIs estimation.ConclusionThe present study, although in a proof-of-concept animal model, shows that vitreous metabolomics can be a powerful tool to predict PMI providing a more accurate estimation compared to the widely studied approach based on vitreous potassium concentrations.
RECIFS: a centralized geo-environmental database for coral reef research and conservation
Authors: Selmoni Oliver , Lecellier Gaël , Berteaux-Lecellier Véronique , Joost Stéphane 
Published: October 2022

AbstractHost to intricated networks of marine species, coral reefs are among the most biologically diverse ecosystems on Earth. Over the past decades, major degradations of coral reefs have been observed worldwide, which is largely attributed to the effects of climate change and local stressors related to human activities. Now more than ever, characterizing how the environment shapes the dynamics of the reef ecosystem is key to (1) uncovering the environmental drivers of reef degradation, and (2) enforcing efficient conservation strategies in response. To achieve these objectives, it is pivotal that environmental data characterizing such ecosystem dynamics, which occur across specific spatial and temporal scales, are easily accessible to coral reef researchers and conservation stakeholders alike.Here we present the Reef Environment Centralized Information System (RECIFS), an online repository of datasets describing reef environments worldwide over the past few decades.The data served through RECIFS originate from remote sensed datasets available in the public domain, and characterize various facets of the reef environment, including water chemistry and physics (e.g. temperature, pH, chlorophyll concentration), as well as anthropogenic local pressures (e.g. boat detection, distance from agricultural or urban areas). The datasets from RECIFS can be accessed at different spatial and temporal resolutions and are delivered through an intuitive web-application featuring an interactive map requiring no prior knowledge working with remote sensing or geographic information systems. The RECIFS web-application is available in complete open access athttps://recifs.epfl.ch.We describe two case studies showing possible implementations of RECIFS to 1) characterize coral diversity in the Caribbean and 2) investigate local adaptation of a reef fish population in Northwest Australia.
TORC1 is an essential regulator of nutrient-dependent differentiation inLeishmania
Authors: Myburgh Elmarie , Geoghegan Vincent , Alves-Ferreira Eliza V.C. , Nievas Y. Romina , Grewal Jaspreet S. , Brown Elaine , McLuskey Karen , Mottram Jeremy C. 
Published: October 2022

SUMMARYLeishmaniaparasites undergo differentiation between various proliferating and non-dividing forms to adapt to changing host environments. The mechanisms that link environmental cues with the parasite’s developmental changes remain elusive. Here, we report thatLeishmaniaTORC1 is a key environmental sensor for parasite differentiation in the sand fly-stage promastigotes and for replication of mammalian-stage amastigotes. We show thatLeishmaniaRPTOR1, interacts with TOR1 and LST8. We investigate TORC1 function by conditional deletion ofRPTOR1, where under nutrient rich conditions RPTOR1 depletion results in decreased protein synthesis and growth, G1 cell cycle arrest and premature differentiation from proliferative promastigotes to non-dividing mammalian-infective metacyclic forms. These parasites cannot develop into proliferative amastigotes in the mammalian host, or respond to nutrients to differentiate to proliferative retroleptomonads, which are required for their blood-meal induced amplification in sand flies and enhanced mammalian infectivity. RPTOR1-dependent TORC1 functionality represents a critical mechanism for driving parasite growth and proliferation.
Simulation of Gilbert Theory for Self-Association in Sedimentation Velocity Experiments: A Guide to Evaluate Best Fitting Models
Authors: Bishop GR , Correia JJ 
Published: October 2022

AbstractThere is a long tradition in the Biophysics community of using simulations as a means to understand macromolecular behavior in various physicochemical methods. This allows a rigorous means to interpret observations in terms of fundamental principles, including chemical equilibrium, reaction kinetics, transport processes and thermodynamics. Here we simulate data for the Gilbert Theory for self-association, a fundamental analytical ultracentrifuge (AUC) technique to understand the shape of sedimentation velocity reaction boundaries that involve reversible monomer-Nmer interactions. Simulating monomer-dimer through monomer-hexamer systems as a function of concentration about the equilibrium constant allows a visual means to differentiate reaction stoichiometry by determining end points and inflexion positions. Including intermediates (eg A1-A2-A3-A4-A5-A6) in the simulations reveals the smoothing of the reaction boundary and the removal of sharp inflexions between monomers and polymers. The addition of cooperativity restores sharp boundaries or peaks to the observation and allows more discrimination in the selection of possible fitting models. Thermodynamic nonideality adds additional features when applied across wide ranges of concentration that might be appropriate for high concentration therapeutic monoclonal antibody (mAb) solutions. This presentation serves as a tutorial for using modern AUC analysis software like SEDANAL for selecting potential fitting models.
ROCK2 Knockout Improves Proliferation Rate in a Cellular Model of Down Syndrome
Authors: LeBlanc-Straceski Janine , Williams Riley , Ward Kylie , Bates Autumn , Duran Catherine , Anderson Lordina , Murray Morgan , Pereira-Badji Jennifer , Shoushani Christina , Thibault Jacob 
Published: October 2022

ABSTRACTIn a cellular model of Down Syndrome, hTERT immortalized RPE-1 (human retinal pigment epithelial-1) cells carrying an extra copy of chromosome 21 exhibit reduced fitness, in part, as an increase in doubling time (or a reduction in cell proliferation rate) in culture. ROCK2 (Rho associated coiled-coil containing kinase 2) was identified in a whole genome CRISPR knockout (KO) screen designed to identify genes and pathways that could be therapeutically targeted to improve cell proliferation (Replogle JM, et al. manuscript in preparation). ROCK2 KO cell lines of both RPE-1 euploid and trisomy 21 aneuploid cells were created using CRISPR. Trisomy 21 ROCK2 KO cell lines showed a modest increase in cell proliferation rate compared to the parental aneuploid cells, similar to the relative effect that ROCK2 knockout had in the whole genome CRISPR screen. Euploid ROCK2 KO cell lines showed no difference in growth rate vs their ROCK2 expressing counterparts. Changes in doubling time in response to two pharmaceutical ROCK inhibitors, Fasudil and Y27632, also showed the same modest increase in cell proliferation rate in the trisomy 21 cells. The actin cytoskeleton, a target of ROCK2 regulation, exhibited long stress fibers that aligned across multiple contiguous cells in confluent trisomy 21 ROCK2 KO cells compared to the disorganized stress fibers of the parental trisomy 21 cells with normal ROCK2 expression.
Dynamics of BMP signaling in the earlyDrosophilaembryo
Authors: Al Asafen Hadel Y. , Beseli Aydin , Hiremath Sharva , Williams Cranos M. , Reeves Gregory T. 
Published: October 2022

AbstractIn developing tissues, morphogen gradients are thought to initialize gene expression patterns. However, the relationship between the dynamics of morphogen-encoded signals and gene expression decisions are largely unknown. Here we examine the dynamics of the Bone Morphogenetic Protein (BMP) pathway inDrosophilablastoderm-stage embryos. In this tissue, the BMP pathway is highly dynamic: it begins as a broad and weak signal on the dorsal half of the embryo, then 20-30 min later refines into a narrow, intense peak centered on the dorsal midline. This dynamical progression of the BMP signal raises questions of how it stably activates target genes. Therefore, we performed live imaging of the BMP signal and found that dorsal-lateral cells experience only a short transient in BMP signaling, after which the signal is lost completely. Moreover, we measured the transcriptional response of the BMP target genepannierin live embryos and found it to remain activated in dorsal-lateral cells, even after the BMP signal is lost. Our findings may suggest that the BMP pathway activates a memory, or “ratchet” mechanism that may sustain gene expression.
Insights into H2O2-induced signaling in Jurkat cells from analysis of gene expression
Authors: Taylor Megan F. , Black Michael A. , Hampton Mark B. , Ledgerwood Elizabeth C. 
Published: October 2022

AbstractHydrogen peroxide (H2O2) is a ubiquitous oxidant produced in a regulated manner by various enzymes in mammalian cells. H2O2reversibly oxidises thiol groups of cysteine residues to mediate intracellular signalling. Whilst examples of H2O2dependent signalling have been reported, the exact molecular mechanism(s) of signalling and the pathways affected are not well understood. Here, the transcriptomic response of Jurkat T cells to H2O2was investigated to determine global effects on gene expression. With a low H2O2concentration (10 μM) that did not induced an oxidative stress response or cell death, extensive changes in gene expression occurred after 4 hours (6803 differentially expressed genes). Of the genes with greater then 2-fold change in expression, 85% were upregulated suggesting that in a physiological setting H2O2predominantly activates gene expression. Pathway analysis identified gene expression signatures associated with FOXO and NTRK signalling. These signatures were associated with an overlapping set of transcriptional regulators. Overall, our results provide a snapshot of gene expression changes in response to H2O2, which, along with further studies, will lead to new insights into the specific pathways that are activated in response to endogenous production of H2O2, and the molecular mechanisms of H2O2signalling.
Mitotic chromosomes scale to nucleo-cytoplasmic ratio and cell size inXenopus
Authors: Zhou Coral Y. , Dekker Bastiaan , Liu Ziyuan , Cabrera Hilda , Ryan Joel , Dekker Job , Heald Rebecca 
Published: October 2022

AbstractDuring the rapid and reductive cleavage divisions of early embryogenesis, subcellular structures such as the nucleus and mitotic spindle scale to decreasing cell size. Mitotic chromosomes also decrease in size during development, presumably to coordinately scale with mitotic spindles, but underlying mechanisms are unclear. Here we combinein vivoandin vitroapproaches using eggs and embryos from the frogXenopus laevisto show that mitotic chromosome scaling is mechanistically distinct from other forms of subcellular scaling. We found that mitotic chromosomes scale continuously with cell, spindle and nuclear sizein vivo. However, unlike for spindles and nuclei, mitotic chromosome size cannot be re-set by cytoplasmic factors from earlier developmental stages.In vitro, increasing nucleo-cytoplasmic (N/C) ratio is sufficient to recapitulate mitotic chromosome scaling, but not nuclear or spindle scaling, through differential loading of maternal factors during interphase. An additional pathway involving importin α scales mitotic chromosomes to cell surface area/volume (SA/V) during metaphase. Finally, single-chromosome immunofluorescence and analysis of Hi-C data suggest that mitotic chromosomes scale through decreased recruitment of condensin I, resulting in major rearrangements of DNA loop architecture to accommodate the same amount of DNA on a shorter axis. Together, our findings demonstrate how mitotic chromosome size is set by spatially and temporally distinct developmental cues in the early embryo.
Neural predictors of subjective fear depend on the situation
Authors: Wang Yiyu , Kragel Philip A. , Satpute Ajay B. 
Published: October 2022

ABSTRSCTThe extent to which neural representations of fear experience depend on or generalize across the situational context has remained unclear. We systematically manipulated variation within and across three distinct fearevocative situations including fear of heights, spiders, and social threats. Participants (n=21, 10 females and 11 males) viewed 20 second clips depicting spiders, heights, or social encounters, and rated fear after each video. Searchlight multivoxel pattern analysis (MVPA) was used to identify whether and which brain regions carry information that predicts fear experience, and the degree to which the fear-predictive neural codes in these areas depend upon or generalize across the situations. The overwhelming majority of brain regions carrying information about fear did so in a situation dependent manner. These findings suggest that local neural representations of fear experience are unlikely to involve a singular pattern, but rather a collection of multiple heterogeneous brain states
MdrDB: Mutation-induced drug resistance DataBase
Authors: Yang Ziyi , Ye Zhaofeng , Qiu Jiezhong , Feng Rongjun , Li Danyu , Hsieh Changyu , Allcock Jonathan , Zhang Sheng-Yu 
Published: October 2022

AbstractMutation-induced drug resistance – where the efficacy of drugs is diminished by structural changes in proteins – presents a significant challenge to drug development and the clinical treatment of disease. Understanding the effects of mutation on protein-ligand binding affinities is a key step in developing more effective drugs and therapies, but as a research community we are currently hindered by the lack of a comprehensive database of relevant information. To address this issue, we have developed MdrDB, a database of information related to changes in protein-ligand affinity caused by mutations in protein structure. MdrDB combines data from seven publicly available datasets with calculated biochemical features, as well as 3D structures computed with PyMOL and AlphaFold 2.0, to form the largest database of its kind. With 3D structural information provided for all samples, MdrDB was specifically created to have the size, breadth, and complexity to be useful for practical protein mutation studies and drug resistance modeling. The database brings together wild type and mutant protein-ligand complexes, binding affinity changes upon mutation (ΔΔG), and biochemical features calculated from complexes to advance our understanding of mutation-induced drug resistance, the development of combination therapies, and the discovery of novel chemicals. In total, MdrDB contains 100,537 samples generated from 240 proteins (5,119 total PDB structures), 2,503 mutations, and 440 drugs. Of the total samples, 95,971 are based on available PDB structures, with the remaining 4,566 based on AlphaFold 2.0 predicted structures.
Perceptions of COVID-19 risk, vaccine access, and confidence: a qualitative analysis of South Asians in Canada
Authors: Kandasamy Sujane , Manoharan Baanu , Khan Zainab , Stennett Rosain , Desai Dipika , Nocos Rochelle , Wahi Gita , Banner Davina , de Souza Russell J. , Lear Scott A. , Anand Sonia S. 
Published: October 2022

AbstractVISUAL ABSTRACT CAN BE FOUNDHEREObjectivesIn the first full year of the COVID-19 pandemic (2020), South Asians living in the Greater Toronto Hamilton and Vancouver Areas experienced specific barriers to accessing SARS-CoV-2 testing and receiving reliable health information. However, between June 2021 and February 2022, the proportion of people having received at least 1 dose of a COVID-19 vaccine was higher among this group (96%) than among individuals who were not visible minorities (93%). A better understanding of successful approaches and the challenges experienced by those who remain unvaccinated among this highly vaccinated group may improve public health outreach in subsequent waves of the current pandemic or for future pandemic planning. Using qualitative methods, we sought to explore the perceptions of COVID-19 risk, vaccine access, uptake, and confidence among South Asians living in Canada.MethodsIn this qualitative study, we interviewed 25 participants between July 2021 and January 2022 in the Greater Toronto Hamilton and Greater Vancouver Areas (10 community members, 9 advocacy group leaders, 6 public health staff). We conducted initial and focused coding in duplicate and developed salient themes. Throughout this process, we held frequent discussions with members of the study’s advisory group to guide data collection as it relates to community engagement, recruitment, and data analysis.ResultsAccess to and confidence in the COVID-19 vaccine was impacted by individual risk perceptions; sources of trusted information (ethnic and non-ethnic); impact of COVID-19 and the pandemic on individuals, families, and society; and experiences with COVID-19 mandates and policies (including temporal and generational differences). Approaches that include community-level awareness and tailored outreach as it relates to language and cultural context were considered successful.ConclusionUnderstanding factors and developing strategies that build vaccine confidence can guide our approach to increase vaccine acceptance in the current and future pandemics.