bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computer vision, causal inference and public health modelling approaches to generate evidence on the impacts of urban planning in non-communicable disease and health inequalities in UK and Australian cities: A proposed collaborative approach
Authors: Hunter Ruth F. , Garcia Leandro , Stevenson Mark , Nice Kerry , Wijnands Jasper S. , Kee Frank , Ellis Geraint , Anderson Neil , Seneviratne Sachith , Moeinaddini Mehdi , Godic Branislava , Akaraci Selin , Thompson Jason 
Published: April 2023

ABSTRACTBackgroundGiven that the majority of the world’s population live in cities, it is essential to global health efforts that we design them in ways that both reduce non-communicable diseases (NCDs) risk and that facilitate adoption and maintenance of healthy lifestyles. Current approaches tend to focus on the relationship between urban design-related factors that affect health at the local or neighbourhood level but few studies have explored this relationship both within and across entire cities, nor explored the causal pathways between urban-designed related factors and NCDs. The aim of this research program is to use computer vision, causal inference, and public health modelling methods for understanding the causal relationship between urban design and health at the neighbourhood level, and to explore intervention approaches at the city scale.MethodsPhase 1 will use machine learning and computer vision techniques to analyse gridded, local-level aerial images (with an optical resolution of <20cm), of all UK and Australian cities with populations over 100,000. It will identify a variety of urban features within these images and derive associations between them and NCD incidence and risk factors identified through location-based health surveys. Phase 2, using data from prospective health cohorts and linked objective built environment data, will apply Bayesian networks to investigate the possible causal pathways between built environment, lifestyle factors, and NCD incidence. Phase 3 will estimate the health impacts of actionable changes in urban design. Using health impact assessment modelling, we will calculate the NCD burden that could be prevented if cities were to adopt urban features of healthier counterparts. A similar approach will be applied on finer-grained scale within all case study cities, enabling assessment of health impacts of changes in individual locations. Phase 4 will develop an interactive web-based toolkit to enable urban designers, planners and policymakers to inform the decision-making cycle, co-designed with intended users involving participatory workshops.DiscussionWe use state-of-the-art approaches to: (i) generate evidence on the impacts of urban planning and design in NCDs and health inequalities in UK and Australian cities, and (ii) provide stakeholders with tools for advocacy and designing healthier cities.Trial registrationNot applicable.
How AlphaFold shaped the structural coverage of the human transmembrane proteome
Authors: Jambrich Márton A. , Tusnady Gabor E. , Dobson Laszlo 
Published: April 2023

AbstractAlphaFold2 (AF2) provides structures for every protein, opening up prospects for virtually every field in structural biology. However, transmembrane proteins pose a challenge for experimental scientists, resulting in a limited number of solved structures. Consequently, algorithms trained on this finite training set also face difficulties. To address this issue, we recently launched the TmAlphaFold database, where predicted AlphaFold2 structures are embedded into the membrane and a quality assessment is provided for each prediction using geometrical evaluation. In this paper, we analyze how AF2 has changed the structural coverage of membrane proteins compared to earlier years when only experimental structures were available, and high-throughput structure prediction was greatly limited. We also evaluate how AF2 can be used to search for (distant) homologs in highly diverse protein families. By combining quality assessment and homology search, we can pinpoint protein families where AF2 accuracy is limited, and experimental approaches are still desired.
Single-cell and spatial transcriptomics identify a macrophage population associated with skeletal muscle fibrosis
Authors: Coulis Gerald , Jaime Diego , Guerrero-Juarez Christian , Kastenschmidt Jenna M. , Farahat Philip K. , Nguyen Quy , Pervolarakis Nicholas , McLinden Katherine , Thurlow Lauren , Movahedi Saba , Duarte Jorge , Sorn Andrew , Montoya Elizabeth , Mozaffar Izza , Dragan Morgan , Othy Shivashankar , Joshi Trupti , Hans Chetan P. , Kimonis Virginia , MacLean Adam L. , Nie Qing , Wallace Lindsay M. , Harper Scott Q. , Mozaffar Tahseen , Hogarth Marshall W. , Bhattacharya Surajit , Jaiswal Jyoti K. , Golann David R. , Su Qi , Kessenbrock Kai , Stec Michael , Spencer Melissa J. , Zamudio Jesse R. , Villalta S. Armando 
Published: April 2023

ABSTRACTThe monocytic/macrophage system is essential for skeletal muscle homeostasis, but its dysregulation contributes to the pathogenesis of muscle degenerative disorders. Despite our increasing knowledge of the role of macrophages in degenerative disease, it still remains unclear how macrophages contribute to muscle fibrosis. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six novel clusters. Unexpectedly, none corresponded to traditional definitions of M1 or M2 macrophage activation. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 and spp1. Spatial transcriptomics and computational inferences of intercellular communication indicated that spp1 regulates stromal progenitor and macrophage interactions during muscular dystrophy. Galectin-3+macrophages were chronically activated in dystrophic muscle and adoptive transfer assays showed that the galectin-3+phenotype was the dominant molecular program induced within the dystrophic milieu. Histological examination of human muscle biopsies revealed that galectin-3+macrophages were also elevated in multiple myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining the transcriptional programs induced in muscle macrophages, and reveal spp1 as a major regulator of macrophage and stromal progenitor interactions.
Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies
Authors: Erdogan Remziye R , Dolatshahi Sepideh 
Published: April 2023

AbstractTransplacental antibody transfer is crucially important in shaping neonatal immunity. Recently, prenatal maternal immunization has been employed to boost pathogen-specific immunoglobulin G (IgG) transfer to the fetus. Multiple factors have been implicated in antibody transfer, but how these key dynamic regulators work together to elicit the observed selectivity is pertinent to engineering vaccines for mothers to optimally immunize their newborns. Here, we present the first quantitative mechanistic model to uncover the determinants of placental antibody transfer and inform personalized immunization approaches. We identified placental FcγRIIb expressed by endothelial cells as a limiting factor in receptor-mediated transfer, which plays a key role in promoting preferential transport of subclasses IgG1, IgG3, and IgG4, but not IgG2. Integrated computational modeling andin vitroexperiments reveal that IgG subclass abundance, Fc receptor (FcR) binding affinity, and FcR abundance in syncytiotrophoblasts and endothelial cells contribute to inter-subclass competition and potentially inter-and intra-patient antibody transfer heterogeneity. We developed anin silicoprenatal vaccine testbed by combining a computational model of maternal vaccination with this placental transfer model using the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine as a case study. Model simulations unveiled precision prenatal immunization opportunities that account for a patient’s anticipated gestational length, placental size, and FcR expression by modulating vaccine timing, dosage, and adjuvant. This computational approach provides new perspectives on the dynamics of maternal-fetal antibody transfer in humans and potential avenues to optimize prenatal vaccinations that promote neonatal immunity.
Development and calibration of the FSPM CPlantBox to represent the interactions between water and carbon fluxes in the soil-plant-atmosphere continuum
Authors: Giraud M. , Le Gall S. , Harings M. , Javaux M. , Leitner D. , Meunier F. , Rothfuss Y. , van Dusschoten D. , Vanderborght J. , Vereecken H. , Lobet G. , Schnepf A. 
Published: April 2023

AbstractA plant’s development is strongly linked to the water and carbon flows in the soil-plant-atmosphere continuum. Expected climate shifts will alter the water and carbon cycles and will affect plant phenotypes. Comprehensive models which simulate mechanistically and dynamically the feedback loops between a plant’s three-dimensional development and the water and carbon flows are useful tools to evaluate the sustainability of genotype-environment-management combinations which do not yet exist. In this study, we present the latest version of the open-source three-dimensional Functional-Structural Plant Model CPlantBox with PiafMunch and DuMuxcoupling. We simulated semi-mechanistically the development of generic C3 monocots from 10 to 25 days after sowing and undergoing an atmospheric dry spell of one week (no precipitation). We compared the results for dry spells starting on different days (day 11 or 18) and with different climates (wetter and colder against drier and warmer atmospheric and initial soil conditions). Compared with the wetter and colder climate, the dry spell with the drier and warmer climate led to a lower instantaneous water use efficiency. Moreover, the lower symplasm turgor for the drier and warmer climate limited the growth, which made the sucrose available for other processes, such as maintenance respiration. Both of these effects were stronger for the later dry spell compared with the early dry spell under the drier and warmer climate. We could thus use CPlantBox to simulate diverging emerging processes (like carbon partitioning) defining the plants’ phenotypic plasticity response to their environment.
Anti-diarrheal drug loperamide induces dysbiosis in zebrafish microbiota via bacterial inhibition
Authors: Stevick Rebecca J. , Bedu Sébastien , Dray Nicolas , Ghigo Jean-Marc , Pérez-Pascual David 
Published: April 2023

AbstractBackgroundPerturbations of animal-associated microbiomes from chemical stress can affect host physiology and health. While dysbiosis induced by antibiotic treatments and disease are well known, chemical, non-antibiotic drugs have recently been shown to induce changes in microbiome composition, warranting further exploration. Loperamide is an opioid-receptor agonist drug widely prescribed drug for treating acute diarrhea in humans. Loperamide is also used as a tool to study the impact of bowel dysfunction in animal models by inducing constipation, but its effect on host-associated microbiota is poorly characterized.ResultsWe used conventional and gnotobiotic larval zebrafish models to show that in addition to host-specific effects, loperamide also has anti-bacterial activities that directly induce changes in microbiota diversity. This dysbiosis is due to changes in bacterial colonization, since germ-free zebrafish mono-reconventionalized with bacterial strains sensitive to loperamide are colonized up to 100-fold lower when treated with loperamide. Consistently, the bacterial diversity of gnotobiotic zebrafish colonized by a mix of representative bacterial strains is affected by loperamide treatment.ConclusionOur results demonstrate that loperamide, in addition to host effects, also induces dysbiosis in a vertebrate model, highlighting that established treatments can have underlooked secondary effects on microbiota structure and function. This study further provides a insights for future studies exploring how common medications directly induce changes in host-associated microbiota.Graphical Abstract
DMC1stabilizes synapsis and crossover at high and low temperatures during wheat meiosis
Authors: Draeger Tracie N. , Rey María-Dolores , Hayta Sadiye , Smedley Mark , Martín Azahara C. , Moore Graham 
Published: April 2023

AbstractEffective chromosome synapsis and crossover during meiosis are essential for fertility, especially in grain crops such as wheat. These processes function most efficiently in wheat at temperatures between 17-23 °C, although the genetic mechanisms for such temperature dependence are unknown. In a previously identified mutant of the hexaploid wheat reference variety ‘Chinese Spring’ lacking the long arm of chromosome 5D, exposure to low temperatures during meiosis resulted in asynapsis and crossover failure. In a second mutant (ttmei1), containing a 4 Mb deletion in chromosome 5DL, exposure to 13 °C led to similarly high levels of asynapsis and univalence. Moreover, exposure to 30 °C led to a significant, but less extreme effect on crossover. Previously, we proposed that, of 41 genes deleted in this 4 Mb region, the major meiotic geneTaDMC1-D1was the most likely candidate for preservation of synapsis and crossover at low (and possibly high) temperatures. In the current study, using RNA-guided Cas9, we developed a new Chinese Spring CRISPR mutant, containing a 39 bp deletion in the 5D copy ofDMC1, representing the first reported CRISPR-Cas9 targeted mutagenesis in Chinese Spring, and the first CRISPR mutant forDMC1in wheat. In controlled environment experiments, wild-type Chinese Spring, CRISPRdmc1-D1and backcrossedttmei1mutants were exposed to either high or low temperatures during the temperature-sensitive period from premeiotic interphase to early meiosis I. After 6-7 days at 13 °C, crossover decreased by over 95% in thedmc1-D1mutants, when compared with wild-type plants grown under the same conditions. After 24 hours at 30 °C,dmc1-D1mutants exhibited a reduced number of crossovers and increased univalence, although these differences were less marked than at 13 °C. Similar results were obtained forttmei1mutants, although their scores were more variable, possibly reflecting higher levels of background mutation. These experiments confirm our previous hypothesis thatDMC1-D1is responsible for preservation of normal synapsis and crossover at low and, to a certain extent, high temperatures. Given that reductions in crossover have significant effects on grain yield, these results have important implications for wheat breeding, particularly in the face of climate change.Key messageThe meiotic recombination geneDMC1on wheat chromosome 5D preserves normal chromosome synapsis and crossover during periods of high and low temperature.
Growth balance analysis models of cyanobacteria for understanding resource allocation strategies
Authors: Ghaffarinasab Sajjad , Lercher Martin J. , Dourado Hugo 
Published: April 2023

AbstractCyanobacteria have emerged as attractive microbial cell factories, as they can convert atmospheric CO2and sunlight into valuable chemicals. To increase their growth and productivity, one should aim to optimize the allocation of limited cellular resources across different metabolic processes. Here, we developed two growth balance analysis (GBA) models for the cyanobacteriumSynechocystissp. PCC 6803. In its biological assumptions, the models closely related to an existing coarse-grained model, while its mathematical formulation is heavily streamlined. We show that the GBA models provide virtually identical predictions about cellular resource allocation among photosynthesis, carbon metabolism, and the protein translation machinery under different environmental conditions as the previous, mathematically more involved model. Our model also captures the effects of photodamage on proteome allocation and the resulting growth rates. We further show how the GBA model can be easily extended to include more reactions, leading to a second GBA model capable of new predictions about the cellular resource allocation. Balanced growth models of the type presented here can easily expanded to include more biological details, providing a useful toolbox for the understanding of the physiological capabilities of cyanobacteria, their allocation of cellular resources, and the potential of their bioengineering for optimized biomass production.
TDP-1 and FUST-1 co-inhibit exon inclusion and control fertility together with transcriptional regulation
Authors: Taylor Morgan , Marx Olivia , Norris Adam 
Published: April 2023

ABSTRACTGene expression is a multistep, carefully controlled process, and crosstalk between regulatory layers plays an important role in coordinating gene expression. To identify functionally relevant coordination between transcriptional and post-transcriptional gene regulation, we performed a systematic reverse-genetic interaction screen inC. elegans. We combined RNA binding protein (RBP) and transcription factor (TF) mutants, creating over 100 RBP; TF double mutants. This screen identified a variety of unexpected double mutant phenotypes, including two strong genetic interactions between the ALS-related RBPs,fust-1andtdp-1, and the homeodomain TFceh-14. Losing any one of these genes alone has no significant effect on the health of the organism. However,fust-1; ceh-14andtdp-1; ceh-14double mutants both exhibit strong temperature-sensitive fertility defects. Both double mutants exhibit defects in gonad morphology, sperm function, and oocyte function. RNA-seq analysis of double mutants identifiesceh-14as the main controller of transcript levels, whilefust-1andtdp-1control splicing through a shared role in exon inhibition. We identify a cassette exon in the polyglutamine-repeat proteinpqn-41whichtdp-1inhibits. Loss oftdp-1causes thepqn-41exon to be aberrantly included, and forced skipping of this exon intdp-1; ceh-14double mutants rescues fertility. Together our findings identify a novel shared physiological role forfust-1andtdp-1in promotingC. elegansfertility in aceh-14mutant background and reveal a shared molecular function offust-1andtdp-1in exon inhibition.
The small RNA component of Arabidopsis phloem sap and its response to iron deficiency
Authors: Bakirbas Ahmet , Castro-Rodriguez Rosario , Walker Elsbeth L. 
Published: April 2023

AbstractIn order to discover sRNA that might function during iron deficiency stress, RNA was prepared from phloem exudates ofArabidopsis thaliana. Bioanalyzer results indicate that abundant RNA from phloem is small in size—less than 200 nt. Moreover, typical rRNA bands were not observed. Sequencing of eight independent phloem RNA samples indicated that that tRNA-derived fragments, specifically 5’ tRFs and 5’ tRNA halves, are highly abundant in phloem sap, comprising about 46% of all reads. In addition, a set of miRNAs that are present in phloem sap was defined, and several miRNA and sRNAs were identified that are differentially expressed during iron deficiency.HighlightPreparation of RNA from Arabidopsis phloem sap revealed thatmost of the RNA is small (less than 200 nt)tRNA fragments (tRFs) are highly abundanta set of miRNAs present in phloem sap can be defined
Uncovering protein-protein interactions of the human sodium channel Nav1.7
Authors: Zhou Xuelong , Zhao Jing 
Published: April 2023

AbstractThe voltage-gated sodium channel Nav1.7 plays a crucial role in the initiation and propagation of pain signals. Our previous study has successfully identified the interacting proteins of mouse Nav1.7 (mNav1.7). In this study, we aimed to further elucidate the protein-protein interactions associated with human Nav1.7 (hNav1.7). Stable epitope (TAP)-tagged HEK293 cells expressing hNaV1.7 were utilized for the identification of hNav1.7-interacting proteins. The hNaV1.7-associated complexes were isolated through tandem affinity purification and further characterized by mass spectrometry.Bioinformatics analysis was carried out using the PANTHER classification system. Electrophysiological recording was performed to assess Nav1.7 current. Tap-tagged hNav1.7 was expressed effectively in HEK293 cells, exhibiting normal functional Nav1.7 currents. A total of 261 proteins were identified as interactors of hNav1.7, mainly located across the cell membrane and cytoplasm, and primarily involved in biological processes related to protein translation and expression. Comparison between human and mouse Nav1.7-interacting proteins revealed shared proteins (such as Eef1a1, Eef2, Tcp1, Cct2, Cct3, Cct5, Cct6a, and Cct7) as well as protein families (such as kinesin and Rab GTPases family). Knockdown of two of the shared interacting proteins, CCT5 and TMED10, resulted in reduced Nav1.7 current density. In conclusion, the protein interactions of hNaV1.7 were successfully mapped in the current work. These novel findings offer essential insights into the regulatory mechanisms that govern Nav1.7 function.Significance statementChronic pain affects approximately 20% of the world’s population and is a global major public health problem. Nav1.7 has been recognized as a promising target for novel analgesics. However, the drug development process for Nav1.7 is challenging. A thorough understanding of the regulatory mechanism of Nav1.7 would greatly assist in the development of its analgesic drugs. Our previous work successfully mapped the mNav1.7 protein interactions. In the current study, the interacting proteins of hNav1.7 were further defined. Our findings provide important implications for the development of Nav1.7-based analgesics for human use.
Deep imaging revealed dynamics and signaling in one-to-one pollen tube guidance
Authors: Mizuta Yoko , Sakakibara Daigo , Nagahara Shiori , Kaneshiro Ikuma , Nagae Takuya T. , Kurihara Daisuke , Higashiyama Tetsuya 
Published: April 2023

ABSTRACTIn angiosperms, pollen tube guidance allows sperm cell delivery to the female gametes within the ovule, which are deeply embedded in a flower. However, when an ovary includes multiple pollen tubes and ovules, it is unclear how each ovule is fertilized one-to-one by a pollen tube. Here, our two-photon imaging revealed the pollen tube dynamics in living ovaries. The number of pollen tubes and ovule maturity affected the target selection among multiple ovules. On the inner surface of the septum epidermis within the transmitting tract, pollen tube behavior and emergence were regulated by the ovular sporophytic signals. In funicular guidance, the second pollen tube was strictly repelled by the FERONIA and LORELEI-dependent gametophytic signal, especially more than 45 minutes after the first pollen tube had passed. Such highly spatiotemporal regulation mechanisms in the one-to-one pollen tube guidance may allow angiosperms to produce more offspring in nature.