bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Highly-Efficient, Scalable Pipeline for Fixed Feature Extraction from Large-Scale High-Content Imaging Screens
Authors: Comolet Gabriel , Bose Neeloy , Winchell Jeff , Duren-Lubanski Alyssa , Rusielewicz Tom , Goldberg Jordan , Horn Grayson , Paull Daniel , Migliori Bianca 
Published: July 2023

AbstractLeveraging artificial intelligence (AI) in image-based morphological profiling of cell populations is proving increasingly valuable for identifying diseased states and drug responses in high-content imaging (HCI) screens. When the differences between populations (such as a healthy and diseased) are completely unknown and undistinguishable by the human eye, it is crucial that HCI screens are large in scale, allowing numerous replicates for developing reliable models, as well as accounting for confounding factors such as individual (donor) and intra-experimental variation. However, as screen sizes increase, challenges arise including the lack of scalable solutions for analyzing high-dimensional datasets and processing the results in a timely manner. For this purpose, many tools have been developed to reduce images into a set of features using unbiased methods, such as embedding vectors extracted from pre-trained neural networks or autoencoders. While these methods preserve most of the predictive power contained in each image despite reducing the dimensionality significantly, they do not provide easily interpretable information. Alternatively, techniques to extract specific cellular features from data are typically slow, difficult to scale, and often produce redundant outputs, which can lead to the model learning from irrelevant data, which might distort future predictions. Here we present ScaleFEx℠, a memory efficient and scalable open-source Python pipeline that extracts biologically meaningful features from large high-content imaging datasets. It requires only modest computational resources but can also be deployed on high-powered cloud computing infrastructure. ScaleFEx℠ can be used in conjunction with AI models to cluster data and subsequently explore, identify, and rank features to provide insights into the morphological hallmarks of the phenotypic categories. We demonstrate the performance of this tool on a dataset consisting of control and drug-treated cells from a cohort of 20 donors, benchmarking it against the state-of-the-art tool, CellProfiler, and analyze the features underlying the phenotypic shift induced by chemical compounds. In addition, the tools generalizability and utility is shown in the analysis of publicly available datasets. Overall, ScaleFEx℠ constitutes a robust and compact pipeline for identifying the effects of drugs on morphological phenotypes and defining interpretable features that can be leveraged in disease profiling and drug discovery.
Prolonged T cell – DC macro-clustering within lymph node microenvironments initiates Th2 cell differentiation in a site-specific manner
Authors: Lyons-Cohen Miranda R. , Shamskhou Elya A. , Gerner Michael Y. 
Published: July 2023

SummaryFormation of T helper 2 (Th2) responses has been attributed to low-grade T cell stimulation, yet how large-scale polyclonal Th2 responses are generatedin vivoremains unclear. Here, we used quantitative imaging to investigate early Th2 differentiation within lymph nodes (LNs) following cutaneous allergen administration. Contrary to current models, Th2 differentiation was associated with enhanced T cell activation and extensive integrin-dependent ‘macro-clustering’ at the T-B border, which also contrasted clustering behavior seen during Th1 differentiation. Unexpectedly, formation of Th2 macro-clusters within LNs was highly dependent on the site of skin sensitization. Differences between sites were driven by divergent activation states of migratory cDC2 from different dermal tissues, with enhanced costimulatory molecule expression by cDC2 in Th2-generating LNs promoting T cell macro-clustering and cytokine sensing. Thus, generation of dedicated priming micro-environments through enhanced costimulatory molecule signaling initiates the generation of Th2 responsesin vivoand occurs in a skin site-specific manner.
Efficient High-Quality Metagenome Assembly from Long Accurate Reads using Minimizer-space de Bruijn Graphs
Authors: Benoit Gaëtan , Raguideau Sébastien , James Robert , Phillippy Adam M. , Chikhi Rayan , Quince Christopher 
Published: July 2023

AbstractWe introduce a novel metagenomics assembler for high-accuracy long reads. Our approach, implemented as metaMDBG, combines highly efficient de Bruijn graph assembly in minimizer space, with both a multi-k′ approach for dealing with variations in genome coverage depth and an abundance-based filtering strategy for simplifying strain complexity. The resulting algorithm is more efficient than the state-of-the-art but with better assembly results. metaMDBG was 1.5 to 12 times faster than competing assemblers and requires between one-tenth and one-thirtieth of the memory across a range of data sets. We obtained up to twice as many high-quality circularised prokaryotic metagenome assembled genomes (MAGs) on the most complex communities, and a better recovery of viruses and plasmids. metaMDBG performs particularly well for abundant organisms whilst being robust to the presence of strain diversity. The result is that for the first time it is possible to efficiently reconstruct the majority of complex communities by abundance as nearcomplete MAGs.
α-carboxysome size is controlled by the disordered scaffold protein CsoS2
Authors: Oltrogge Luke M. , Chen Allen W. , Chaijarasphong Thawatchai , Turnšek Julia B. , Savage David F. 
Published: July 2023

AbstractCarboxysomes are protein microcompartments that function in the bacterial CO2concentrating mechanism (CCM) to facilitate CO2assimilation. To do so, carboxysomes assemble from thousands of constituent proteins into an icosahedral shell which encapsulates the enzymes rubisco and carbonic anhydrase to form structures typically >100 nm and >300 megadaltons. Although many of the protein interactions driving the assembly process have been determined, it remains unknown how size and composition are precisely controlled. Here we show that the size of α-carboxysomes is controlled by the disordered scaffolding protein CsoS2. CsoS2 contains two classes of related peptide repeats which bind to the shell in a distinct fashion, and our data indicate that size is controlled by the relative number of these interactions. We propose an energetic and structural model wherein the two repeat classes bind at the junction of shell hexamers but differ in their preferences for the shell contact angles, and thus the local curvature. In total, this model suggests that a set of specific and repeated interactions between CsoS2 and shell proteins collectively achieve the large size and monodispersity of α-carboxysomes.
Diversity loss in microbial ecosystems undergoing gradual environmental changes
Authors: Berger Aviad , Harari Maya Gatt , Gross Avner , Erez Amir 
Published: July 2023

AbstractMicrobial ecosystems in soils, oceans, and other environments are essential for global ecological stability. Environmental shifts are anticipated to trigger destabilizing events across the planet. In this study, we model how gradual environmental changes impact ecosystems, specifically when leading to a loss of diversity. We investigate how an ecosystem, within a serial-dilution setup, relaxes to a stable steady state. Our results reveal that as an ecosystem approaches its loss of diversity transition, its dynamics slow down. Consequently, diverse ecosystems, such as tropical rainforest soils, gradually driven past their transition point may exhibit a significant response lag. This suggests that some ecosystems may be closer to a collapse in diversity than current observations indicate. Although our model does not capture the full complexity of real-world ecosystems, it highlights critical aspects underlying the loss of biodiversity in changing environments. This has potential implications for empirical studies and when planning interventions.
Structural basis for lipid transfer by the ATG2A-ATG9A complex
Authors: Wang Yang , Dahmane Selma , Ti Rujuan , Mai Xinyi , Zhu Lizhe , Carlson Lars-Anders , Stjepanovic Goran 
Published: July 2023

AbstractAutophagy is characterized by the formation of double-membrane vesicles called autophagosomes. ATG2A and ATG9A play an essential role in autophagy by mediating lipid transfer and re-equilibration between membranes for autophagosome formation. Here we report the cryo-EM structures of human ATG2A-WIPI4 complex at 3.2 Å, and ATG2A-WIPI4-ATG9A complex at 7 Å resolution. The ATG2A structure is characterized by a central hydrophobic cavity formed by a network of β-strands that facilitates lipid transfer, and highly flexible N- and C-terminal domains. Molecular dynamics simulations of the ATG2A N-terminal domain revealed the mechanism of lipid-extraction from the donor membranes while the ATG2A-ATG9A complex structure provides insights into the later stages of the lipid transfer reaction. ATG9A-ATG2A structural analysis revealed a 1:1 stoichiometry, directly aligning the ATG9A lateral pore with ATG2A lipid transfer cavity, hence allowing for a direct transfer of lipids from ATG2A. The ATG9A trimer can interact with both N- and C-terminal tip of rod-shaped ATG2A. Cryo-electron tomography of ATG2A-liposome binding states shows that ATG2A tethers lipid vesicles at different orientations. In summary, this study provides a molecular basis for the growth of the phagophore membrane, and lends structural insights into spatially coupled lipid transport and re-equilibration during autophagosome formation.
Disruption of outdoor activities caused by wildfire smoke shapes circulation of respiratory pathogens
Authors: Arregui García Beatriz , Ascione Claudio , Pera Arianna , Stocco Davide , Wang Boxuan , Valdano Eugenio , Pullano Giulia 
Published: July 2023

AbstractThe consequences of wildfires on public health extend beyond injury. Smoke can traverse vast distances, compromising air quality in unaffected areas and exacerbating chronic respiratory conditions. But smoke may affect the circulation and burden of communicable diseases, too. The disruption in air quality and adherence to safety guidelines can impact the time people spend indoors, and this in turns may increase exposure to airborne pathogens like influenza, SARS-CoV-2, RSV. However, the quantification of such disruptions and their implications for the transmission of respiratory diseases remain unclear. Here we study the effects of smoke generated by severe wildfires in the U.S. states of California, Oregon, Washington in September 2020. We assess the impact on human behavior and the potential consequences for the emergence of respiratory diseases. Our findings reveal a significant shift towards indoor activities in counties within Oregon and Washington during wildfires. However, a discernible change in mobility patterns is not evident in California. This discrepancy may arise from the familiarity of Californian residents with wildfires and air quality index alerts, which have become integrated into their daily routines. Consequently, their mobility patterns may be less affected during such incidents compared to individuals in other regions. We then use a deterministic compartmental model of epidemic spread to quantify the impact of the describe behavioral changes on epidemic circulation. We found that counties with disrupted air exhibited higher cumulated and peak incidence of cases compared to unaffected counties, with the exception of California. Additionally, we found that flu-like epidemics – low reproduction ratio and short generation time – are most affected by the behavioral changes under study. Our findings may help improve public health response in a context of larger, more frequent wildfires triggered by climate change.
Real-time targeted illumination in widefield microscopy achieves confocal quality neuronal images
Authors: Wang Yao L. , Fan Jia , Chung Samuel H. 
Published: July 2023

AbstractWidefield fluorescence imaging has significant challenges in visualizing neuronal fibers near cell bodies. Specifically, out-of-focus and scattered light from the bright cellbody often obscures nearby dim fibers and degrades their signal-to-background ratio. Scanning techniques can solve this problem but are limited by reduced imaging speed and increased cost. We greatly reduce stray light by modulating the illumination intensity to different structures. We use a digital micromirror device in the illumination channel of a common widefield microscope and use real-time image processing to pattern the illumination. With the setup, we illuminate bright cell bodies with minimal light intensity, and illuminate in focus fiber-like structures with high light intensity to reveal weak signals. Thus, we minimize the background and enhance the visibility of fibers in the final image. This targeted illumination significantly improves fiber contrast while maintaining a fast-imaging speed and low cost. Using a targeted illumination setup in a widefield microscope, we demonstrate confocal quality imaging of complex neurons in liveC. elegansand zebrafish larva, as well as inin vitromice brain slice.
Structure of the human Duffy antigen receptor
Authors: Saha Shirsha , Khanppnavar Basavraj , Maharana Jagannath , Kim Heeryung , Carino Carlo Marion C. , Daly Carole , Houston Shane , Kumari Poonam , Yadav Prem N. , Plouffe Bianca , Inoue Asuka , Chung Ka Young , Banerjee Ramanuj , Korkhov Volodymyr M. , Shukla Arun K. 
Published: July 2023

AbstractThe Duffy antigen receptor, also known as FY glycoprotein or CD234, is a seven transmembrane protein expressed primarily at the surface of red blood cells, which displays promiscuous binding to multiple chemokines. Not only does it serve as the basis of the Duffy blood group system but it also acts as the primary attachment site for malarial parasitePlasmodium vivaxon erythrocytes and as one of the nucleating receptors for the pore forming toxins secreted byStaphylococcus aureus. Despite a predicted 7TM architecture and efficient binding to a spectrum of chemokines, it fails to exhibit canonical second messenger response such as calcium release, likely due to a lack of G protein coupling. Unlike prototypical GPCRs and β-arrestin-biased atypical chemokine receptors, the Duffy antigen receptor also appears to lack β-arrestin binding, making it an enigmatic 7TM chemokine receptor. In order to decipher the molecular mechanism of this intriguing functional divergence exhibited by the Duffy antigen receptor, we have determined its cryo-EM structure in complex with a C-C type chemokine, CCL7. The structure reveals a relatively superficial binding mode of CCL7, with the N-terminus of the receptor serving as the key interaction interface, and a partially formed orthosteric binding pocket lacking the second site for chemokine recognition compared to prototypical chemokine receptors. The structural framework allows us to employ HDX-MS approach to uncover ligand-induced structural changes in the receptor and draw important insights into the promiscuous nature of chemokine binding. Interestingly, we also observe a dramatic shortening of TM5 and 6 on the intracellular side, compared to prototypical GPCRs, which precludes the coupling of canonical signal-transducers namely G proteins, GRKs and β-arrestins, as demonstrated through extensive cellular assays. Taken together, our study uncovers a previously unknown structural mechanism that imparts unique functional divergence on the 7TM fold encoded in the Duffy antigen receptor while maintaining its scavenging function and should facilitate the designing of novel therapeutics targeting this receptor.
Education and Later-life Mortality: Evidence from a School Reform in Japan
Authors: Masuda Kazuya , Shigeoka Hitoshi 
Published: July 2023

AbstractWe examine the mortality effects of a 1947 school reform in Japan, which extended compulsory schooling from primary to secondary school by as much as 3 years. The abolition of secondary school fees also indicates that those affected by the reform likely came from disadvantaged families who could have benefited the most from schooling. Even in this relatively favorable setting, we fail to find that the reform improved later-life mortality up to the age of 87 years, although it significantly increased years of schooling. This finding suggests limited health returns to schooling at the lower level of educational attainment.
“Putting the power back into community”: A mixed methods evaluation of a chronic hepatitis B training course for the Aboriginal health workforce of Australia’s Northern Territory
Authors: Hosking Kelly , De Santis Teresa , Vintour-Cesar Emily , Merrdi Wilson Phillip , Bunn Linda , Garambaka Gurruwiwi George , Wurrawilya Shiraline , Mariyalawuy Bukulatjpi Sarah , Nelson Sandra , Stuart-Carter Kelly-Anne , Ngurruwuthun Terese , Dhagapan Amanda , Binks Paula , Sullivan Richard , Ward Linda , Schroder Phoebe , Tate-Baker Jaclyn , Davis Joshua S , Connors Christine , Davies Jane 
Published: July 2023

BackgroundChronic hepatitis B (CHB) is endemic in the Aboriginal and Torres Strait Islander population of Australia’s Northern Territory. Progression to liver disease can be prevented if holistic care is provided. Low health literacy amongst health professionals is a known barrier to caring for people living with CHB. We co-designed and delivered a culturally safe “Managing hepatitis B” training course for the Aboriginal health workforce. Here we present an evaluation of the course.ObjectivesTo improve course participants CHB-related knowledge, attitudes, and clinical practice.To evaluate the “Managing hepatitis B” training course.To enable participants to have the skills and confidence to be part of the care team.MethodsWe used participatory action research and culturally safe principles. We used purpose-built quantitative and qualitative evaluation tools to evaluate our “Managing hepatitis B” training course. We integrated the two forms of data, deductively analysing codes, grouped into categories, and assessed pedagogical outcomes against Kirkpatrick’s training evaluation framework.ResultsEight courses were delivered between 2019 and 2023, with 130 participants from 32 communities. Pre- and post-course questionnaires demonstrated statistically significant improvements in all domains, p<0.001 on 93 matched pairs. Thematic network analysis demonstrated high levels of course acceptability and significant knowledge acquisition. Other themes identified include cultural safety, shame, previous misinformation, and misconceptions about transmission. Observations demonstrate improvements in post-course engagement, a deep understanding of CHB as well as increased participation in clinical care teams.ConclusionsThe “Managing hepatitis B” training course led to a sustained improvement in the knowledge and attitudes of the Aboriginal health workforce, resulting in improved care and treatment uptake for people living with CHB. Important non-clinical outcomes included strengthening teaching, and leadership skills, and empowerment.
Incorrect Versus Correct Mask Utilization in Public Places
Authors: Heston Thomas F 
Published: July 2023

AbstractMask usage was mandated by public health authorities globally to decrease the spread of COVID-19. These recommendations were based on data showing that N95 masks and possibly surgical masks, when worn tight against the face, help slow the transmission of the SARS-CoV-2 virus. However, cloth and loose-fitting surgical masks are greatly inferior.MethodsMask use by a random observation of 100 people in public indoor facilities was recorded and statistically analyzed.ResultsOut of 100 people wearing a mask, 37 wore a cloth mask. Another 36 people wore a loosely applied surgical mask. Only 27 people wore a surgical mask that covered the nose and mouth and was applied firmly against the face at its margins. There were no people seen wearing an N95 mask. Overall, people were about 70% more likely to wear a surgical mask than a cloth mask (63 vs 37, p < 0.05). Of those wearing a surgical mask, more people wore it loosely than properly (36 to 27, p=0.17). Overall, people were more likely to wear a cloth mask or improperly applied surgical mask than a properly fitted one (73 vs 27, p < 0.001).ConclusionIn public settings, using cloth or loose-fitting surgical masks was almost 3 times more common than adequately using a tight-fitting surgical mask. Out of the 100 people observed, none wore an N95 respirator mask.
Genome-Wide Association Study for Yield and Yield related traits reveals Marker–Trait Associations in Germplasm lines of Rice
Authors: Shivani Darmagaru , Rahaman Abdul Fiyaz , Jabeen Farzana , Kumar Jukanti Aravind , Kasarla Chaithanya , Dhananjaya Dileep Kumar Gowdru , Subba Rao Lella Venkata , Supriya  , Venkatanagappa Shoba , Sundaram Raman Meenakshi 
Published: July 2023

AbstractRice germplasm has abundant genetic diversity, which provides a feasible solution for mapping loci of multiple traits simultaneously. In this study, a set of 72 rice germplasm lines were evaluated for yield and yield-related traits, and significant phenotypic variation was observed among the lines. Three accessions with high yield performance were identified. The germplasm set comprised five sub-populations and genome-wide association study (GWAS) identified a total of 6 marker-trait associations (MTAs) for the studied traits. These MTAs were located on rice chromosomes 1, 3, 7, 9, and 12 and explained the trait phenotypic variances ranging from 17.8 to 26.3%. Six novel MTAs were identified for yield and yield-related traits. A total of 28 putative annotated candidate genes were identified in a genomic region spanning ∼200 kb around the MTAs respectively. Among the important genes underlying the novel MTAs wereOsFBK12, bHLH, WRKY, HVA22,andZmEBE-1, which are known to be associated with the identified novel QTLs. These MTAs provide a pathway for improving high yield in rice genotypes through molecular breeding.
3-hydroxykynurenine is a ROS-inducing cytotoxic tryptophan metabolite that disrupts the TCA cycle
Authors: Buchanan Jane L. , Rauckhorst Adam J. , Taylor Eric B. 
Published: July 2023

AbstractTryptophan is an essential amino acid that is extensively characterized as a regulator of cellular function through its metabolism by indoleamine 2,3-deoxygenase (IDO) into the kynurenine pathway. However, despite decades of research on tryptophan metabolism, the metabolic regulatory roles of it and its metabolites are not well understood. To address this, we performed an activity metabolomics screen of tryptophan and most of its known metabolites in cell culture. We discovered that treatment of human colon cancer cells (HCT116) with 3-hydroxykynurenine (3-HK), a metabolite of kynurenine, potently disrupted TCA cycle function. Citrate and aconitate levels were increased, while isocitrate and all downstream TCA metabolites were decreased, suggesting decreased aconitase function. We hypothesized that 3HK or one of its metabolites increased reactive oxygen species (ROS) and inhibited aconitase activity. Accordingly, we observed almost complete depletion of reduced glutathione and a decrease in total glutathione levels. We observed a dose-dependent decrease in cell viability after 48 hours of 3HK treatment. These data suggest that raising the intracellular levels of 3HK could be sufficient to induce ROS-mediated apoptosis. We modulated the intracellular levels of 3HK by combined induction of IDO and knockdown of kynureninase (KYNU) in HCT116 cells. Cell viability decreased significantly after 48 hours of KYNU knockdown compared to controls, which was accompanied by increased ROS production and Annexin V staining revealing apoptosis. Finally, we identify xanthommatin production from 3-HK as a candidate radical-producing, cytotoxic mechanism. Our work indicates that KYNU may be a target for disrupting tryptophan metabolism. Interestingly, many cancers exhibit overexpression of IDO, providing a cancer-specific metabolic vulnerability that could be exploited by KYNU inhibition.