bluuebunny/crossref_metadata_2025 huggingface dataset:
Zebrafish use conserved CLR and TLR signaling pathways to respond to fungal PAMPs in zymosan
Authors: Glass Erin , Robinson Stephan L. , Rosowski Emily E.
Published: June 2024

Pattern recognition receptors (PRRs) such as C-type lectin receptors (CLRs) and Toll-like receptors (TLRs) are used by hosts to recognize pathogen-associated molecular patterns (PAMPs) in microorganisms and to initiate innate immune responses. While PRRs exist across invertebrate and vertebrate species, the functional homology of many of these receptors is still unclear. In this study, we investigate the innate immune response of zebrafish larvae to zymosan, a β-glucan-containing particle derived from fungal cell walls. Macrophages and neutrophils robustly respond to zymosan and are required for zymosan-induced activation of the NF-κB transcription factor. Full activation of NF-κB in response to zymosan depends on Card9/Syk and Myd88, conserved CLR and TLR adaptor proteins, respectively. Two putative CLRs, Clec4c and Sclra, are both required for maximal sensing of zymosan and NF-κB activation. Altogether, we identify conserved PRRs and PRR signaling pathways in larval zebrafish that promote recognition of fungal PAMPs. These results inform modeling of human fungal infections in zebrafish and increase our knowledge of the evolution and conservation of PRR pathways in vertebrates.
Estimates of molecular convergence reveal pleiotropic genes underlying adaptive variation across teleost fish
Authors: Barua Agneesh , Beinsteiner Brice , Laudet Vincent , Robinson-Rechavi Marc
Published: June 2024

Teleosts are the most diverse group of vertebrates on earth. Their diversity is a testament to the combined effects of genetic, developmental, and evolutionary forces. However, disentangling the interactions between these forces is challenging due to the complexity of the genotype-phenotype relationship and the masking of adaptive genetic signals by genetic noise. Estimates of molecular convergence where changes in the sequence of protein-coding genes lead to identical amino acid substitution across multiple lineages provide strong evidence of adaptive evolution. In this study, we estimated signals for molecular convergence in protein-coding genes across 143 teleost genomes to identify genes and processes that experienced adaptive changes. We find that genes with signals of molecular convergence are implicated in diverse processes ranging from embryonic development, tissue morphogenesis, metabolism, to hormone and heat response. Some convergent substitutions are located on functionally important sites on proteins potentially providing the molecular basis for adaptations to hypoxia, salinity fluctuations, and varying skeletal morphologies. Additionally, single-cell RNA sequencing data from zebrafish showed that the convergent genes have dynamic expression across various cell types during embryonic development. These results highlight the functional importance of the convergent genes as well as their pleiotropic nature. Although traditionally considered a source of genetic constraint, we argue that adaptation via changes in pleiotropic genes are particularly advantageous during periods of ecological shifts. We present the pleiotropic release model which describes how adaptive variation on pleiotropic genes can have large fitness effects, allowing organisms to overcome selective pressures during periods of ecological shifts.
Origin, Trophic Transfer And Recycling Of Particulate Organic Matter In The Waters Of Two Upwelling Bays Of Humboldt Current System: Insights From Compound-Specific Isotopic Compositions Of Amino Acids
Authors: Srain B.M , Valdés J , Camaño A
Published: June 2024

Particulate organic matter (POM) is considered the primary source of N and C in the ocean. In pelagic marine environments, POM consists of algae and detrital nitrogen, with amino acids representing the largest chemical fraction. Currently, measurements of the isotopic distributions of N atoms in amino acids are considered powerful tools for exploring and determining the metabolic sources involved in the synthesis and degradation of organic matter. In this study, we measured the δ15N of amino acid signatures (δ15N-AA) in suspended and sinking POM collected from two upwelling bays in northern Chile, to examine isotopic enrichment patterns and gain insights into the origins, trophic transfer, and heterotrophic reworking of this organic fraction. At Mejillones Bay, the δ15N-AA values of suspended POM ranged from 5 ‰ to 27 ‰, while at Antofagasta Bay, these values oscillated between 9 ‰ and 24 ‰. The sinking POM collected from sediment traps exhibited values and isotopic fractionation patterns similar to those observed in the deeper layers of the water columns in both bays. The enrichment patterns of δ15N-phenylalanine and δ15N-NO-demonstrated the autochthonous character of the POM and its predominantly marine origin at both bays. The parameters trophic transfer (ΔTr) and heterotrophic reworking (ΣV) indicated that the heterotrophic recycling of POM occurs more intensively at through the oxyclines. Furthermore, these parameters revealed an enhanced trophic transfer magnitude and higher heterotrophic re-synthesis of POM in the waters of Mejillones Bay, resulting in a lower flux of exported POM than that observed in Antofagasta Bay. These differences highlight the spatial heterogeneous nature of organic matter transfer and reworking processes in this upwelling system.
Spatial fingerprint of consumer body size and habitat preference on resource distribution
Authors: Little Chelsea J. , Banville Pierre Etienne , Ford Adam T. , Germain Rachel M.
Published: June 2024

Consumers shape spatial patterns on landscapes by amplifying or dampening environmental heterogeneity through feeding, excretion, and movement of resources. The degree to which the environment is modified by consumers depends on species’ traits, including body mass, movement behavior, sociality, and habitat specialization. Global change is altering the size and traits of consumer populations, but our understanding of how this may impact resource heterogeneity is limited. Here, we developed an individual-based model of habitat specialists’ and generalists’ movement and activity in a patchy landscape and investigated the impact of changes in population and mean body sizes on landscape-scale resource heterogeneity. We found that consumers specializing on low-resource habitats (a common risk avoidance strategy) increased spatial resource heterogeneity regardless of their population and body size. By contrast, generalists eroded differences among habitats, and we further found that resource heterogeneity decreased with the average body size of generalist consumers, even while controlling for total consumer biomass. These nuanced spatial outcomes of consumer-resource interactions emerge from the unique metabolic demands of specialists vs. generalists, which scale nonlinearly with body size. Since global change disproportionately impacts larger species and specialists, indirect consequences on ecosystems may arise via biotic processes, affecting spatial heterogeneity of future landscapes.
Survey-Based Analysis of a Science of Science Communication Scientific Interest Group: Member Feedback and Perspectives on Science Communication
Authors: Hilliard Anna J. , Sugden Nicola , Bass Kristin M. , Gunter Chris
Published: June 2024

Coordinated attempts to promote systematic approaches to the design and evaluation of science communication efforts have generally lagged behind the proliferation and diversification of those efforts. To address this, we founded the US National Institutes of Health (NIH) Science of Science Communication Scientific Interest Group (SciOSciComm-SIG) and undertook a mixed-methods survey-based evaluation of the group one year after its founding. Respondents indicated ongoing interest and some participation in public-facing science communication while identifying specific barriers, and praised the role of the SIG in expanding access to information about evidence-based practices.
Therapeutic liver cell transplantation to treat a genetic liver defect
Authors: Willimann Melanie , Grisch-Chan Hiu Man , Rimann Nicole , Rothgangl Tanja , Hruzova Martina , Schwank Gerald , Thöny Beat
Published: June 2024

For gene therapy of the liver,in vivoapplications based on adeno-associated virus are the most advanced vectors despite limitations, including low efficacy and episomal loss, potential integration and safety issues, and high production costs. Alternative vectors and/or delivery routes are of high interest. The regenerative ability of the liver bears the potential forex vivotherapy using liver cell transplantation for disease correction if provided with a selective advantage to expand and replace the existing cell mass. Here we present such treatment of a mouse model of human of phenylketonuria (PKU). Primary hepatocytes from wild-type mice were gene modifiedin vitro(with a lentiviral vector) that carries a gene editing system (CRISPR) to inhibitCypor.Cyporinactivation confers paracetamol (or acetaminophen) resistance to hepatocytes and thus a growth advantage to eliminate the pre-existing liver cells upon grafting (via the spleen) and exposure to repeated treatment with paracetamol. GraftingCypor-inactivated wild-type hepatocytes into inbred young adultenu2(PKU) mice, followed by selective expansion by paracetamol dosing resulted in replacing up to 5% of cell mass, normalization of blood phenylalanine and permanent correction of PKU. Hepatocyte transplantation offers thus an armamentarium of novel therapy options for genetic liver defects.
Does COVID-19 Increase the Risk of Subsequent Kidney Diseases More Than Influenza? A Retrospective Cohort Study Using Real-World Data In the United States
Authors: Zhang Yue , Ghahramani Nasrollah , Chinchilli Vernon M. , Ba Djibril M.
Published: June 2024

Background

Although case reports and observational studies suggest Coronavirus disease 2019 (COVID-19) increases the risk of kidney diseases, definitive real-world evidence, especially in comparison with influenza, is lacking. Our study aims to assess the association between COVID-19 infections and subsequent kidney diseases, using influenza as a positive control and incorporating a negative control to establish clearer associations.

Methods

A large retrospective cohort study with strata matching was conducted using the MarketScan database with records from Jan. 2020 to Dec. 2021. We used the international classification of 10th revision (ICD-10) codes to identify individuals and build three cohorts, (1) COVID-19 group, with index dates as the diagnosis dates of COVID-19; (2) Influenza but no COVID-19 (positive control) group, with index dates as the diagnosis dates of Influenza; and (3) no COVID-19 / Influenza (negative control) group, with randomly assigned index dates between Jan. 2020 to Dec. 2021. The main outcomes were acute kidney injury (AKI), chronic kidney disease (CKD), and end-stage renal disease (ESRD). To evaluate the association between COVID-19 and the new onset of kidney diseases relative to both control groups, we employed multivariable stratified Cox proportional hazards regression analysis.

Results

The study included 939,241 individuals with COVID-19, 1,878,482 individuals in the negative control group, and 199,071 individuals with influenza. After adjusting for demographics, comorbidities, and medication histories, COVID-19 was significantly associated with increased risks of AKI (adjusted hazards ratio, aHR: 2.74, 2.61-2.87), CKD (aHR: 1.38, 1.32-1.45), and ESRD (aHR, 3.22; 95% CI, 2.67-3.88), while influenza was associated with a modestly increased risk of AKI (aHR: 1.24, 1.11-1.38) and had no impact on CKD (aHR: 1.03, 0.92-1.14), and ESRD (aHR, 0.84; 95% CI, 0.55-1.29). Time-specific analyses indicated that while the HR for AKI declined from 0-180 days to 0-540 days, the HR for CKD and ESRD remained stable, with COVID-19’s risk surpassing influenza’s risk throughout follow-up. Exploratory analysis also found significant impacts of COVID-19 on glomerular diseases (aHR 1.28, 95% CI 1.09-1.50).

Conclusion

In this large real-world study, COVID-19 infections were associated with a 2.3-fold risk of developing AKI, a 1.4-fold risk of CKD, and a 4.7-fold risk of ESRD compared to influenza. Greater attention needs to be paid to kidney diseases in individuals after contracting COVID-19 to prevent future adverse health outcomes.
Understanding the implementation of antimicrobial resistance policies in Vietnam: a multilayer analysis of the veterinary drug value chain
Authors: Bâtie Chloé , Duy Nguyen Van , Minh Khue Nguyen Thi , Peyre Marisa , Bordier Marion , Dien Nguyen Thi , Ton Vu Dinh , Goutard Flavie
Published: June 2024

Abstract

Reducing antibiotic use in livestock production has been a target for national action plans worldwide. The Vietnamese livestock plan issued in 2017 has, among other objectives, strengthened the regulatory framework for antibiotic use. While a progressive ban on prophylactic antibiotics in feed and the introduction of mandatory prescriptions have been introduced, the level of implementation of these measures remains unknown. This study explores the level of understanding, acceptance, and application of these regulations among veterinary drug value chain stakeholders. An iterative stakeholder mapping and analysis of the veterinary drug value chain was conducted in north and south Vietnam. We organized one focus group discussion in Hanoi with 12 participants and conducted 39 semi-structured interviews with governmental authorities, national research centers, foreign partners, and private stakeholders along the value chain. The discourses were analyzed to (1) map the veterinary drug value chain and interactions among stakeholders, (2) analyze stakeholder’s technical and social capital regarding regulations, and (3) identify factors influencing their implementation. From the map of the veterinary drug value chain, we identified 30 categories of stakeholders. Based on the map, the capital, and the analysis of the discourse, we identified 10 factors that could influence their implementation. These factors included stakeholder perception of the new regulations, their level of knowledge, the availability of technical guidance, conflict of economic interest between stakeholders, scale-related management discrepancies, the technical and financial barriers to the implementation of the regulations at the local level, the presence of an informal distribution channel, international influence, consumer demand for food safety, and the willingness to reduce the burden of antibiotic resistance. It was clearly identified that new regulations are a necessary step to reducing antibiotic usage in Vietnam, but that the lack of local stakeholder involvement combined with technical constraints were barriers to their implementation. The study underlined the need for greater involvement of local stakeholders in the development of regulations as well as the need to mainstream innovations developed by small producers.
A human-specific, concerted repression of microcephaly genes contributes to radiation-induced growth defects in forebrain organoids
Authors: Ribeiro Jessica Honorato , Etlioglu Emre , Buset Jasmine , Janssen Ann , Puype Hanne , Berden Lisa , Mbouombouo Mfossa André Claude , De Vos Winnok H. , Vermeirssen Vanessa , Baatout Sarah , Rajan Nicholas , Quintens Roel
Published: June 2024

Abstract

Prenatal radiation-induced DNA damage poses a significant threat to normal brain development, resulting in microcephaly which primarily affects the cerebral cortex. It is unclear which molecular mechanisms are at the basis of this defect in humans as the few mechanistic studies performed so far were done in animals. Here, we leveraged human embryonic stem cell- derived forebrain organoids as a model for human corticogenesis. Organoids were X-irradiated with a moderate and a high dose at different time points, representing very early and mid corticogenesis. Irradiation caused a dose- and developmental-timing-dependent reduction in organoid size, which was more prominent in developmentally younger organoids. This coincided with a dose-dependent canonical p53-DREAM-dependent DNA damage response (DDR), consisting of cell cycle arrest, DNA repair and apoptosis. The DDR was delayed and less pronounced in the older organoids. Besides the DDR, we observed radiation-induced premature differentiation of neural progenitors and changes in metabolism. Importantly, our transcriptomic analysis furthermore demonstrated a concerted p53-E2F4-dependent repression of primary microcephaly genes. We found that this was a human-specific feature, as it was not observed in mouse embryonic brains or primary mouse neural progenitor cells. Thus, human forebrain organoids are an excellent model to investigate prenatal DNA damage-induced microcephaly and to uncover potentially targetable human-specific pathways.
MicrosporidianNosema bombycissecretes serine protease inhibitor to suppress host cell apoptosisviacaspase BmICE
Authors: Ran Maoshuang , Bao Jialing , li Boning , Shi Yulian , Yang Wenxin , Meng Xianzhi , Chen Jie , Wei Junhong , Long Mengxian , Li Tian , Li Chunfeng , Pan Guoqing , Zhou Zeyang
Published: June 2024

Microsporidia are a group of intracellular pathogens that actively manipulate host cell biological processes to facilitate their intracellular niche. Apoptosis is an important defense mechanism by which host cell control intracellular pathogens. Microsporidia modulating host cell apoptosis has been reported previously, however the molecular mechanism is not yet clear. In this report, we describe that the microsporidiaNosema bombycisinhibits apoptosis ofBombyx moricells through a secreted protein NbSPN14, which is a serine protease inhibitor (Serpin). An immunofluorescent assay demonstrated that upon infection withN. bombycis, NbSPN14 was initially found in theB. moricell cytoplasm and then became enriched in the host cell nucleus. Overexpression and RNA-interference (RNAi) of NbSPN14 inB. mori’embryo cells confirmed that NbSPN14 inhibited host cell apoptosis. Immunofluorescent and Co-IP assays verified the co-localization and interaction of NbSPN14 with the BmICE, the caspase 3 homolog inB. mori. Knocking out of BmICE or mutating the BmICE-interacting P1 site of NbSPN14, eliminated the localization of NbSPN14 into the host nucleus and prevented the apoptosis-inhibiting effect of NbSPN14, which also proved that the interaction between BmICE and NbSPN14 occurred in host cytoplasm and the NbSPN14 translocation into host cell nucleus is dependent on BmICE. These data elucidate thatN. bombycissecretory protein NbSPN14 inhibits host cell apoptosis by directly inhibiting the caspase protease BmICE, which provides an important insight for understanding pathogen-host interactions and a potential therapeutic target forN. bombycisproliferation.

Author Summary

Microsporidia constitute a class of eukaryotic pathogens that exclusively reside within host cells. The speciesNosema bombycisis the first microsporidian identified as the pathogen of silkworm Pébrine disease. In our research, we discovered howN. bombyciscleverly evades the host’s defenses. It has developed a strategy to survive inside host cells by manipulating host cell apoptosis, disarming the host cell’s self-destruct mechanism. In this study, we discovered that theN. bombycissecretes a serine protease inhibitor named NbSPN14, which infiltrates the cytoplasm of the host cell. The NbSPN14 interacts with the executioner Caspase protease BmICE within the silkworm’s apoptotic pathway, effectively neutralizing its apoptoic activity and thus curbing the apoptosis of the host cells.
Evidence of horizontal gene transfer and environmental selection impacting antibiotic resistance evolution in soil-dwellingListeria
Authors: Goh Ying-Xian , Balu Anupoju Sai Manohar , Nguyen Anthony , Zhang Hailong , Ponder Monica , Krometis Leigh-Anne , Pruden Amy , Liao Jingqiu
Published: June 2024

Soil has been identified as an important reservoir of antibiotic resistance genes (ARGs) and there is a need to understand how corresponding environmental changes influence their emergence, evolution, and spread. As a soil-dwelling bacterial genus containing important pathogens,Listeria,includingL. monocytogenes, the causative agent of listeriosis in humans, could serve as a key model for establishing this understanding. Notably, acquired antibiotic resistance amongL. monocytogenesisolated from foods and the environment has been observed in some regions over the past decade. Here we characterized ARGs using 594 genomes representing 19Listeriaspecies that we previously isolated from soils across the United States. Among the five putatively functional ARGs identified,lin, which confers resistance to lincomycin, was the most prevalent, followed bymprF, sul, fosX, andnorB. ARGs were found to be predominant inListeria sensu strictospecies and species more closely related toL. monocytogenestended to harbor more ARGs. Notably,lin, fosX,andnorBshowed evidence of recent horizontal gene transfer (HGT) across species, likely through transformation as opposed to conjugation and transduction, whilemprFandsulappear to have undergone positive selection. In addition, soil properties and surrounding land use were identified as the most important factors associated with ARG richness and genetic divergence, respectively. Using machine learning, we demonstrated that the presence of ARGs can be predicted from environmental variables with good accuracy (mean auROC of 0.76). Collectively, our data suggest that recent HGT and environmental selection played a vital role in the acquisition and diversification of ARGs in the soil environment.
The action mechanism of actinoporins revealed through the structure of pore-forming intermediates
Authors: Arranz Rocío , Santiago César , Masiulis Simonas , Rivera-de-Torre Esperanza , Palacios-Ortega Juan , Carlero Diego , Heras-Márquez Diego , Gavilanes José G. , Arias-Palomo Ernesto , Martínez-del-Pozo Álvaro , García-Linares Sara , Martín-Benito Jaime
Published: June 2024

Pore-forming proteins exemplify the transformative potential of biological molecules. Initially produced in a monomeric, water-soluble form, they spontaneously assemble into multimeric integral membrane proteins in the presence of suitable target lipids. Their functions include roles in apoptosis, cell signaling, immunity, as well as attack and defense systems between different organisms. This latter group encompasses actinoporins, a family of pore-forming toxins from sea anemones that kill target cells by perforating their plasma membrane. Here, we have determined the structures of two such toxins, fragaceatoxin C and sticholysin II, in a membrane environment using cryogenic electron microscopy. The structures reveal how dozens of lipid molecules interact in an orderly manner, forming an intrinsic part of the pore. We have also isolated different pore-forming intermediates, where only a fraction of the constituent monomers is incorporated, exhibiting non-closed, arc-shaped structures. Based on these structures we propose a mechanism of action where the sequential assembly of toxin monomers onto the membrane, accompanied by conformational changes, triggers pore formation and membrane perforation. Our results contribute to a better understanding of the transforming capacity of these pore-forming proteins, which are becoming increasingly important for their diverse biotechnological applications.
Native mass spectrometry of membrane protein-lipid interactions in different detergent environments
Authors: Kumar Smriti , Stover Lauren , Wang Lie , Bahramimoghaddam Hanieh , Zhou Ming , Russell David H. , Laganowsky Arthur
Published: June 2024

Native mass spectrometry (MS) is revealing the role of specific lipids in modulating membrane protein structure and function. Membrane proteins solubilized in detergents are often introduced into the mass spectrometer; however, commonly used detergents for structural studies, such as dodecylmaltoside, tend to generate highly charged ions, leading to protein unfolding, thereby diminishing their utility for characterizing protein-lipid interactions. Thus, there is a critical need to develop approaches to investigate protein-lipid interactions in different detergents. Here, we demonstrate how charge-reducing molecules, such as spermine and trimethylamine-N-oxide, enable characterization of lipid binding to the bacterial water channel (AqpZ) and ammonia channel (AmtB) in complex with regulatory protein GlnK in different detergent environments. We find protein-lipid interactions are not only protein-dependent but can also be influenced by the detergent and type of charge-reducing molecule. AqpZ-lipid interactions are enhanced in LDAO (n-dodecyl-N,N-dimethylamine-N-oxide), whereas the interaction of AmtB-GlnK with lipids is comparable among different detergents. A fluorescent lipid binding assay also shows detergent dependence for AqpZ-lipid interactions, consistent with results from native MS. Taken together, native MS will play a pivotal role in establishing optimal experimental parameters that will be invaluable for various applications, such as drug discovery, as well as biochemical and structural investigations.
Misalignment between circadian preference and accelerometer-derived actual sleep-wake cycle is associated with increased risk of cardiometabolic diseases: a prospective cohort study in UK Biobank
Authors: Chen Yue , Geng Tingting , Xu Xinming , Zhang Zhicheng , Huang Lili , Dong Haiyang , Yu Huan , Gao Xiang , Sun Liang
Published: June 2024

Background: Evidence has linked several circadian disruption indicators to adverse health outcomes, however, associations of misalignment between circadian preference and actual sleep-wake cycle with cardiometabolic diseases (CMDs) remains unclear. We aimed to prospectively investigate the associations of the circadian misalignment with CMDs including type 2 diabetes (T2D), chronic heart diseases (CHD), and stroke, and to uncover potential mechanisms linking circadian misalignment and CMDs. Methods: A total of 60,965 participants from the UK Biobank study without baseline CMDs and followed-up for an average of 7.9 years were included in the current analysis. Circadian misalignment was defined as discrepancies between self-reported chronotype and accelerometer-derived midpoint of sleep. Incident CMDs were derived from multiple medical source of data. Cox proportional hazards regression models were used to compute the hazard ratio (HR) and confidence intervals (CIs) on the association between circadian misalignment and incident CMDs. Results: U-shaped associations were found of the circadian misalignment with incident T2D and CHD after adjusting the potential confounders. Compared to individuals with aligned midsleep and circadian preferences, those with advanced and delayed circadian misalignment had higher risks of T2D [HRs (95%CI)s 1.22 (1.03, 1.45) and 1.39 (1.18, 1.62)]. However, only delayed circadian misalignment was significantly associated with an increased risk of CHD [HR (95%CI) 1.16 (1.02, 1.33)]. Liver function, lipid and glucose metabolism, and inflammatory markers partially explained the observed circadian misalignment and CMDs association (mediation proportion 12.3-44.6% for T2D, 8.8-20.5% for CHD). Additionally, early chronotype [HR (95%CI): 1.19 (1.06, 1.34)] rather than late chronotype was associated with an increased risk of incident T2D. Conclusion: Both advanced and delayed circadian misalignment were associated with increased risks of CMDs, suggesting potential benefits of aligning actual sleep-wake cycles with individual circadian preferences.
Healthiness of Foods and Beverages in Outdoor Advertisements in Xela, Guatemala: A Commercial Determinants of Health Interpretation
Authors: Chuvileva Yulia E. , Chew Aiken , Cassidy Omni , Dávila Sophía , Manangan Arie , Rutherford George , Barnoya Joaquin , Ulin Brigette
Published: July 2024

This study measured the spatial exposure to outdoor advertising of foods and beverages (and their healthiness) in central Xela, a Western Guatemalan city that is home to 181,000 people, 65% of whom are indigenous. We geotagged outdoor advertisements (ads) for foods and beverages in a square mile of Xela, coding for the modality of the advertisement, the types of items marketed, and their healthiness: “most healthy,” “middle healthy,” or “least healthy.” We observed 92 commercial-grade outdoor food and beverage ads across eight modalities, with vehicles (52%, 48/92), branded storefronts (25%, 23/92), and bus stops (13%, 12/92) the most prevalent. While all kinds of food and beverage businesses promoted their products on vehicles, branded storefronts were a modality almost exclusively used by soda companies, while bus stops were disproportionately used by fast food restaurants. We also identified 21 home-based ads, 86% (18/21) of which denoted households selling items they produce or make. Commercial-grade ads promoted largely least healthy foods and beverages, while home-based ads largely exposed people to most and middle healthy items. We interpret the results through the Commercial Determinants of Health Framework.
Glycerol Metabolism Contributes to Competition by Oral Streptococci through Production of Hydrogen Peroxide
Authors: Taylor Zachary A. , Chen Ping , Noeparvar Payam , Pham Danniel N. , Walker Alejandro R. , Kitten Todd , Zeng Lin
Published: June 2024

As a biological byproduct from both humans and microbes, glycerol’s contribution to microbial homeostasis in the oral cavity remains understudied. Here we examined glycerol metabolism byStreptococcus sanguinis,a commensal associated with oral health. Genetic mutants of glucose-PTS enzyme II (manL), glycerol metabolism (glpanddhapathways), and transcriptional regulators were characterized with regard to glycerol catabolism, growth, production of hydrogen peroxide (H2O2), transcription, and competition withStreptococcus mutans. Biochemical assays identified theglppathway as a novel source of H2O2production byS. sanguinisthat is independent of pyruvate oxidase (SpxB). Genetic analysis indicated that theglppathway requires glycerol and a transcriptional regulator, GlpR, for expression and is negatively regulated by PTS, but not the catabolite control protein, CcpA. Conversely, deletion of eithermanLorccpAincreased expression ofspxBand a second, H2O2-non-producing glycerol metabolic pathway (dha), indicative of a mode of regulation consistent with conventional carbon catabolite repression (CCR). In a plate-based antagonism assay and competition assays performed with planktonic and biofilm-grown cells, glycerol greatly benefited the competitive fitness ofS. sanguinisagainstS. mutans.Theglppathway appears to be conserved in several commensal streptococci and actively expressed in caries-free plaque samples. Our study suggests that glycerol metabolism plays a more significant role in the ecology of the oral cavity than previously understood. Commensal streptococci, though not able to use glycerol as a sole carbohydrate for growth, benefit from catabolism of glycerol through production of both ATP and H2O2.

Importance

Glycerol is an abundant carbohydrate found in oral cavity, both due to biological activities of humans and microbes, and as a common ingredient of foods and health care products. However, very little is understood regarding the metabolism of glycerol by some of the most abundant oral bacteria, commensal streptococci. This was in part because most streptococci cannot grow on glycerol as the sole carbon source. Here we show thatStreptococcus sanguinis, an oral commensal associated with dental health, can degrade glycerol for persistence and competition through two independent pathways, one of which generates hydrogen peroxide at levels capable of inhibiting a dental pathobiont,Streptococcus mutans. Preliminary studies suggest that several other commensal streptococci are also able to catabolize glycerol, and glycerol-related genes are being actively expressed in human dental plaque samples. Our findings reveal the potential of glycerol to significantly impact microbial homeostasis which warrants further exploration.
A multi-phenotype approach implicatesSH2B3in the genetics of chronic kidney disease
Authors: Tran Kim N. , Sutherland Heidi G. , Mallett Andrew J. , Griffiths Lyn R. , Lea Rodney A.
Published: July 2024

Chronic kidney disease (CKD) is a complex condition with diverse underlying causes that lead to a progressive decline in kidney function. Genome-wide association studies (GWASs) have identified numerous genetic loci associated with CKD, yet much of the genetic basis remains unexplained. Part of the reason is that most GWASs have only assessed kidney function via single biomarkers such as estimated glomerular filtration rate (eGFR). This study employs a novel multi-phenotype approach, combinatorial Principal Component Analysis (cPCA), to better understand the genetic architecture of CKD. Utilizing a discovery cohort of white British individuals from the UK Biobank (n=337,112), we analyzed 21 CKD-related phenotypes using cPCA to generate over 2 million composite phenotypes (CPs). More than 46,000 CPs demonstrated superior performance in classifying clinical CKD compared to any single biomarker, and those CPs were most frequently comprised of eGFR, cystatin C, HbA1c, microalbuminuria, albumin, and LDL. GWASs of the top 1,000 CPs revealed seven novel genetic loci, withCST3andSH2B3successfully replicated in an independent Irish cohort (n=11,106). Notably, the index SNP of theSH2B3gene, which encodes a regulator in immune responses and cytokine signaling, is a loss-of-function variant with a combined beta of −0.046 and a p-value of 3.1E-56. These results highlight the effectiveness of a multi-phenotype approach in GWASs and implicate a novel functional variant in SH2B3 in CKD phenotypes.

TRANSLATIONAL STATEMENT

The application of combinatorial Principal Component Analysis (cPCA) in our study has identifiedSH2B3as a novel genetic locus associated with chronic kidney disease (CKD). This discovery advances our understanding of CKD’s genetic architecture beyond single biomarker analyses, potentially leading to more precise diagnostic tools and personalized treatment strategies. Future research should focus on validating these findings in diverse populations and integrating cPCA-derived biomarkers into clinical practice to enhance CKD prediction and management, ultimately improving patient outcomes.
Moving frame theory of zero-bias photocurrent on the surface of topological insulators
Authors: Jafari S. A.
Published: July 2024

The recent observation of zero-biased photocurrent on the surface of topological insulators allows to spin-orbit-coupled two-dimensional Dirac cones as ideal platforms for the manipulation of the tilt of Dirac cone. We show that the in-plane effective magnetic field B̃ implements a moving frame transformation on the topological insulators' helical surface states. As a result, photo-excited electrons on the surface undergo a Galilean boost proportional to the effective in-plane magnetic field B̃. The boost velocity is transversely proportional to B̃. This explains why the experimentally observed photocurrent depends linearly on B̃. Our theory, while consistent with the observation that at leading order the effect does not depend on the polarization of the incident radiation, at next leading order in B̃ predicts a polarization dependence in both parallel and transverse directions to the polarization. We also predict two induced Fermi-surface effects that can serve as further confirmation of our moving frame theory. Based on the estimated value ζ≈0.34 of the tilt parameter for a magnetic field of B̃∼3T, our geometric picture qualifies the surface Dirac cone of magnetic topological insulators as an accessible platform for the synthesis and experimental investigation of strong analog gravitational phenomena.

Published by the American Physical Society
2024
Illuminating the Bragg intersections as roots of Dirac nodal lines and high-order van Hove singularities
Authors: Akashi Ryosuke
Published: July 2024

We theoretically reexamine nearly uniform electron models with weak crystalline potentials. In particular, we theorize the modulation of the plane-wave branches at linear regions where multiple Bragg planes intersect. Any such linear intersections involve three or more plane-wave branches diffracted by the periodic potential. Small interbranch interactions can yield various crossing and anticrossing singularities with promised breakdown of the quadratic approximation, extending alongside the intersection lines. Most of the intersections run in low-symmetric paths in the Brillouin zone and therefore we cannot completely characterize their electronic states with standard band-structure plotting methods. The present theory reveals a general mechanism in nearly uniform systems to induce the Dirac nodal lines and van Hove singularities with broken quadratic band approximation in three dimensions, which may host a variety of anomalous low-energy electronic properties. We apply the theory to a recently discovered high-temperature superconductor H3S to interpret the enigmatic density-of-state (DOS) peaking therein. The results show how and the continuous saddle points–the source of the peaked DOS–emerge, as well as reveal the companion Dirac nodal lines hidden in the conduction bands.

Published by the American Physical Society
2024
Progressive polymer deformation induced by polar activity and the influence of inertia
Authors: Tejedor Andrés R. , Ramírez Jorge , Ripoll Marisol
Published: July 2024

Polar activity is shown here to induce a progressive local deformation of linear polymer chains, making a clear distinction between head and tail, while the overall chain conformation gets more compact. This breakdown of self-similarity, provoked by the accumulated tension on the polymer backbone induced by the activity, is shown to occur both in the absence and presence of inertia, although it is stronger in the latter case. Other properties like the relaxation time and diffusion are also largely influenced by the presence of a polar activity.

Published by the American Physical Society
2024
Assessing the adequacy of competition in public construction projects
Authors: Hyari Khaled Hesham , Thneibat Mujahed
Published: June 2024

Purpose

Public construction authorities need to evaluate the level of competition in the submitted bids for a certain project before awarding the contract. A lack of adequate competition is a reason for rejecting all bids and reissuing an invitation to bid for the project. This paper aims to present an analysis of the adequacy of competition in public construction projects.

Design/methodology/approach

The paper uses five competition indicators to correlate the level of competition effect obtained with the number of contractors competing for the project. The analysis is based on the bid opening results for 917 public construction projects in Jordan that include 6,309 bids, with an average number of 6.88 bids per project.

Findings

The results illustrate that there is an improvement in the competition effect over the five analyzed competition indicators as the number of bidders increases. However, the rate of improvement decreases with the increase in bidders. The empirical analysis performed does not support the proposition that an optimum number of bidders exists in competitive bidding for construction projects or the proposition that a higher number of bidders may lead to higher bid prices. However, the indicators developed in this study found that at least 5 bidders are recommended and after 8 bidders, the rate of improvement continues at much slower rate.

Originality/value

The current research presented a multifaceted method for assessing the minimum number of bidders needed to ensure a competitive bidding process. Moreover, the research used actual data from 917 public projects.
Artefacts of disaster risk reduction: conceptualizing bottom-up initiatives of climate action in informal settlements
Authors: Lizarralde Gonzalo , Herazo Benjamín , Smith David , Bornstein Lisa , Gould Kevin , Monsalve Elsa , Ordoñez Nicolás , López Adriana , López Oswaldo , Burdiles Roberto , Araneda Claudio , Olivera Andrés
Published: June 2024

Purpose

Disaster risk reduction is of prime importance in informal settlements in the Global South, where several forms of vulnerability coexist. Policy and official programmes, however, rarely respond to the needs and expectations of citizens and local leaders living in these settlements. Even though these agents constantly attempt to reduce risks in their own way, we know very little about their activities, motivations and effective impact on risk reduction. Here we seek to conceptualize bottom-up initiatives to better grasp their origins, limitations and success.

Design/methodology/approach

Through a four-year action-research project in Colombia, Cuba and Chile, we theorize about the production of change by local agents. Through detailed case studies we explored the activism of 17 local leaders. Through narrative analysis we studied their motivations and explanations. Finally, by documenting 22 initiatives, we revealed effective changes in space.

Findings

In the face of risk and disasters, residents and leaders in informal settings engaged in symbolic, physical and social spaces of interaction. Their actions were guided by trust, emotions, time cycles and activism. Local agency was justified by narratives about risk and climate change that differ from those of authorities and scholars.

Research limitations/implications

There is still limited understanding of bottom-up initiatives in informal settings. It is crucial to conceptualize their origins, limitations and success. The focus on three specific countries necessitates further research for broader applicability and understanding.

Practical implications

A better comprehension of bottom-up actions is crucial for informing policies and programmes aimed at reducing risk in informal settings. Stakeholders must recognize the political, social and cultural roles of these actions for more impactful climate action.

Originality/value

We borrow Simon’s concept of “artefact” to introduce the notion of “Artefacts of Disaster Risk Reduction”, providing insights into the multifaceted nature of bottom-up initiatives. We also emphasize the simultaneous political and phenomenological character of these actions, contributing to a deeper understanding of their origins and impact.
Computational study of a dorsolumbar complete burst fracture and its fixation methods
Authors: Moura Rita , Fidalgo Daniel , Oliveira Dulce , Reis Ana Rita , Areias Bruno , Sousa Luísa , Gonçalves João M. , Sousa Henrique , Natal Jorge R.N. , Parente Marco
Published: June 2024

Purpose

During a fall, a significant part of the major forces is absorbed by the dorsolumbar column area. When the applied stresses exceed the yield strength of the bone tissue, fractures can occur in the vertebrae. Vertebral fractures constitute one of the leading causes of trauma-related hospitalizations, accounting for 15% of all admissions. Posterior pedicle screw fixation has become a common method for treating burst fractures. However, physicians remain divided on the number of fixed segments that are needed to improve clinical outcomes. The present work aims to understand the biomechanical impact of different fixation methods, improving surgical treatments.

Design/methodology/approach

A finite element model of the dorsolumbar spine (T11–L3) section, including cartilages, discs and ligaments, was created. The dorsolumbar stability was tested by comparing two different surgical orthopedic treatments for a fractured first lumbar vertebra on the L1 vertebra: the posterior short segment fixation with intermediate screws (PSS) and the posterior long segment fixation (PL). Distinct loads were applied to represent daily activities.

Findings

Results show that both procedures provide acceptable segment fixation, with the PL offering less freedom of movement, making it more stable than the PSS. The PL approach can be the best choice for an unstable fracture as it leads to a stiffer spine segment.

Originality/value

This study introduces a novel computational model designed for the biomechanical analysis of dorsolumbar injuries, aiming to identify the optimal treatment approaches within both clinical and surgical contexts.
Factors that influence secure behaviour while using mobile digital devices
Authors: Spruit Marcel , Oosting Deborah , Kreffer Celine
Published: June 2024

Purpose

The use of mobile digital devices requires secure behaviour while using these devices. To influence this behaviour, one should be able to adequately measure the behaviour. The purpose of this study is to establish a model for measuring secure behaviour, and to use this model to measure the secure behaviour of individuals while using mobile digital devices such as smartphones and laptops.

Design/methodology/approach

Based on a wide-ranging questionnaire (N = 1000), this study investigates the degree of influence that a relatively large number of factors have on secure behaviour while using mobile digital devices. These factors include knowledge and cognitive attitude, but also affective attitude, as well as several types of bias.

Findings

This study has provided a model for measuring secure behaviour. The results of the measurements show that knowledge, bias, cognitive attitude and affective attitude all have impact on secure behaviour while using mobile digital devices. Moreover, none of these factors is of minor importance.

Practical implications

This study shows that it is important to also consider previously undervalued factors, such as affective attitude and various types of bias, when designing interventions to improve secure behaviour while using mobile digital devices.

Originality/value

Most research on secure behaviour has only looked at a small number of influencing factors, usually limited to knowledge and cognitive attitude. This study shows that one needs a more elaborate model for measuring secure behaviour, and that previously undervalued factors have a clear influence on secure behaviour.
Experimental investigation of nanofluid lubrication on surface roughness under MQL aluminum alloy 6061-T6 series in drilling
Authors: MirHosseini Ehsan , Mirjalily Seyed Ali Agha , Ahrar Amir Javad , Oloomi Seyed Amir Abbas , Zare Mohammad Hasan
Published: July 2024

Purpose

This study aims to investigate the impact of varying the number of minimum quantity lubrication (MQL) nozzles, wind pressure, spindle speed and type of lubrication on surface roughness, fatigue life and tool wear in the drilling of aluminum alloy 6061-T6.

Design/methodology/approach

The effect of using different lubricants such as palm oil, graphene/water nanofluid and SiO2/water in the MQL method was compared with flood and dry methods. The lubricant flow and feed rate were kept constant throughout the drilling, while the number of nozzles, wind pressure and spindle speed varied. After preparing the parts, surface roughness, fatigue life and tool wear were measured, and the results were analyzed by ANOVA.

Findings

The results showed that using MQL with four nozzles and graphene/water nanofluid reduced surface roughness by 60%, followed by SiO2 nanofluid at 56%, and then by palm oil at 50%. Increasing the spindle speed in MQL mode with four nozzles using graphene nanofluid decreased surface roughness by 52% and improved fatigue life by 34% compared to the dry mode. SEM results showed that tool wear and deformation rates significantly decreased. Increasing the number of nozzles caused the fluid particles to penetrate the cutting area, resulting in improved tool cooling with lubrication in all directions.

Originality/value

Numerous attempts have been made worldwide to eliminate industrial lubricants due to environmental pollution. In this research, using nanofluid with wind pressure in MQL reduces environmental impacts and production costs while improving the quality of the final workpiece more than flood and dry methods.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-01-2024-0021/