bluuebunny/crossref_metadata_2025_split huggingface dataset:
Red blood cell distribution width/albumin ratio is a novel risk factor of incidence and long-term mortality in chronic heart failure patients: three large cohorts from China and America
Authors: Zhang Lin , Zhou Ying , Wang Kaiyue , Wang Liming , Teka Tekleab , Zhou Jiashun , Zhang Houliang , Fu Xuebin , Zhang Lele , Zhang Xuemei , Fu Zhifei , Han Lifeng , Gao Xiumei 
Published: September 2023

AimsRed blood cell distribution width/albumin ratio (RAR) is a novel parameter associated with inflammation. Previous studies have not focused on the role of RAR in the incidence and long-term prognosis of chronic heart failure (CHF). This study included three cohorts, two prospective and one retrospective study. The aim was to investigate the value of RAR in the incidence of CHF and the long-term prognosis of CHF.MethodsThree cohorts were investigated, including MIMIC, NHANES, and JHDH. The included patients of MIMIC, NHANES, and JHDH were 22,672 from 2001-2012, 60,754 from 1999-2020, and 15,102 from 2021-2022, respectively. According to whether the patients have CHF-related risk factors, the patients were classified into non-CHF, pre-CHF, and CHF groups. The median follow-up time of MIMIC and NHANES was 364 days and 62 months. Logistic regression, Cox regression, restricted cubic spline (RCS), and Kaplan–Meier (KM) curves were used to analyze the value of RAR in CHF patients.ResultIn NHANES, the CHF prevalence in quartiles of RAR (Q1, Q2, Q3, and Q4) were 8.88%, 16.86%, 27.65%, and 46.61%, respectively. MIMIC and JHDH showed a similar trend. Among the non-CHF and CHF patients, the odds ratio (OR) was 1.45 (JHDH 95% CI 1.33-1.58) and 1.93 (NHANES 95% CI 1.41-2.65). In NHANES, the RAR OR value of Q2, Q3 and Q4 were 2.02(CI 1.19-3.43), 3.24(CI 1.95-5.39), and 4.95(CI 2.44-10.02) compared with Q1, respectively. And the OR was 1.05 (MIMIC 95% CI 1.02-1.07) in pre-CHF and CHF patients. The CHF mortality showed an adjusted hazard ratio (HR) is 1.12 (MIMIC 95% CI 1.1-1.14) and 2.26 (NHANES 95% CI 1.52-3.36). KM demonstrates that higher RAR (>3.4 in NHANES and >5.06 in MIMIC) prognoses lead to poor survival in CHF patients. CHF mortality in the 19th quartile of the RAR was 1.4 times higher than in the first quartile, compared with 1.22 times in the red blood cell distribution width (RDW). The 19-quartile mortality curves of the RAR were more stable than RDW and albumin (ALB).ConclusionRAR is an independent risk factor for incidence and all-cause long-term mortality in CHF patients. The predictive value of RAR for all-cause mortality in CHF is superior to ALB and RDW. RAR may be a potential clinical indicator for future treatment of CHF.
Revisiting the trafficking of insulin and its receptor in rat liver:in vivoand cell-free studies
Authors: Tahiri Khadija , Fouque Françoise , Postel-Vinay Marie-Catherine , Desbuquois Bernard 
Published: September 2023

AbstractEndosomes are the main locus where, upon endocytosis in liver cells, insulin and the activated insulin receptor accumulate and insulin is degraded. In this study, ligand and receptor pathways in rat liver have been revisited using analytical subcellular fractionation. Density gradient analysis of microsomal and light mitochondrial fractions confirmed that, uponin vivouptake into liver, [125I]-insulin was rapidly translocated from plasma membranes to endosomes. Internalized [125I]-labeled proinsulin and biotinylated insulin, which are less degraded than insulin in endosomes, were in part transferred to lysosomes. Following injection of native insulin, receptor and ligand were also both translocated from the plasma membrane to endosomes, with a maximum at 15-30 min. Receptor translocation was reversed by 2-3 hours and neither endocytosis nor recycling were affected byin vivocycloheximide treatment. Fractionation of endosomes of insulin-treated rats on density gradients showed that the insulin receptor was recovered at low density, whereas insulin progressively migrated from low to high densities towards the position of acid phosphatase. On SDS polyacrylamide gels, insulin receptor α and β subunits were identified in plasma membrane, endosomal and lysosomal fractions by affinity crosslinking and Western immunoblotting, respectively. Following insulin treatment, insulin receptor expression rapidly decreased in plasma membranes while increasing in endosomes. In a cell-free system, [125I]-insulin was in part transferred from endosomes to lysosomes, as was, with organelle content mixing, [125I]-biotinylated insulin. In summary: 1) the low lysosomal association of [125I]-insulinin vivois linked to its endosomal degradation; 2) upon ligand-induced endocytosis, the insulin receptor progressively segregates from insulin and is recycled; 3) neither endocytosis no recycling of the receptor requires protein synthesis.
Fluorinated cGAMP analogs, which act as STING agonists and are not cleavable by poxins: structural basis of their function
Authors: Klima Martin , Dejmek Milan , Duchoslav Vojtech , Eisenreichova Andrea , Sala Michal , Chalupsky Karel , Chalupska Dominika , Novotná Barbora , Birkuš Gabriel , Nencka Radim , Boura Evzen 
Published: September 2023

AbstractThe Stimulator of Interferon Genes (STING) plays a crucial role in the cGAS-STING pathway of innate immunity, detecting DNA in the cytoplasm and defending against certain cancers, viruses, and bacteria. We designed and synthesized fluorinated carbocyclic cGAMP analogs, MD1203 and MD1202D (MDs), to enhance their stability against nucleases and their affinity for STING. These compounds demonstrated exceptional activity against wild-type STING and all its allelic variations, including the hard-to-target REF isoform. Despite their distinct chemical modifications relative to the canonical CDNs, such as the substitution of guanine with hypoxanthine and the fluorination of the (pseudo)ribose ring, crystallographic analysis revealed a consistent binding mode with STING. Importantly, these compounds were resistant to cleavage by viral poxin nucleases. The crystallographic analysis of poxin/MD complexes unveiled their binding mode at the interface of poxin monomers, with dynamic adenine base orientations. Interestingly, MDs-bound poxin adopted an unliganded-like conformation, distinct from the conformation of cGAMP-bound poxin. Moreover, when MDs were in complex with poxin, they exhibited a different conformation than cGAMP when bound to poxin; in fact, it closely resembled the conformation observed when MDs were bound to STING. In conclusion, the development of MD1203 and MD1202D, showcases their potential as potent STING activators with remarkable stability against poxin-mediated degradation—a crucial characteristic for future development of antivirals.
Optogenetic control of a GEF of RhoA uncovers a signaling switch from retraction to protrusion
Authors: De Seze Jean , Bongaerts Maud , Boulevard Benoit , Coppey Mathieu 
Published: September 2023

SummaryThe ability of a single protein to trigger different functions is an assumed key feature of cell signaling, yet there are very few examples demonstrating it. Here, using an optogenetic tool to control membrane localization of RhoA nucleotide exchange factors (GEFs), we present a case where the same protein can trigger both protrusion and retraction when recruited to the plasma membrane, polarizing the cell in two opposite directions. We show that the basal concentration of the GEF prior to activation predicts the resulting phenotype. A low concentration leads to retraction, whereas a high concentration triggers protrusion. This unexpected protruding behavior arises from the simultaneous activation of Cdc42 by the GEF and sequestration of active RhoA by the GEF PH domain at high concentrations. We propose a minimal model that recapitulates the phenotypic switch, and we use its predictions to control the two phenotypes within selected cells by adjusting the frequency of light pulses. Our work exemplifies a unique case of control of antagonist phenotypes by a single protein that switches its function based on its concentration or dynamics of activity. It raises numerous open questions about the link between signaling protein and function, particularly in contexts where proteins are highly overexpressed, as often observed in cancer.
Effects of forest urbanization on the interplay between small mammal communities and their gut microbiota
Authors: Bouilloud Marie , Galan Maxime , Pradel Julien , Loiseau Anne , Ferrero Julien , Gallet Romain , Roche Benjamin , Charbonnel Nathalie 
Published: September 2023

AbstractUrbanization significantly impacts wild populations, favoring urban dweller species over those that are unable to adapt to rapid and abrupt changes. One possible explanation for differential adaptative abilities between these species is that the microbiome may modulate the host phenotype rapidly through a high degree of flexibility. Conversely, under such anthropic perturbations, the microbiota composition of some species could be disrupted, resulting in dysbiosis and negative impacts on host fitness, potentially causing local extirpation. The links between the impact of urbanization on host communities and their gut microbiota have only been scarcely explored. In this study, we tested the hypothesis that the gut microbiota (GM) could play a role in host adaptation to urban environments. We addressed this question by studying several species of small terrestrial mammals sampled in forested areas along a forested gradient of urbanization (from rural forests to urban parks) during 2020 fall. The gut was collected and bacteria were described using a 16S metabarcoding approach. We tested whether urbanization led to changes in small mammal communities and in their GM. We analyzed these changes in terms of the presence and abundance of taxa and their putative functions to decipher the processes underlying these changes. We found that urbanization had marked impacts on small mammal communities and their GM, either directly or indirectly depending on small mammal species categories. The urban dweller species had a lower taxonomic diversity but a higher functional diversity and a different composition compared to urban adapter species. Their GM assembly was mostly governed by stochastic effects, which could indicate dysbiosis in these urban species. Selection processes and an overabundance of functions were detected that could be associated with adaptation to urban environments despite potential dysbiosis. Urbanization could also impact the diversity and taxonomic composition of GM in urban adapter species. However, their functional diversity and composition remained relatively stable. This observation can be explained by functional redundancy, where certain taxa express the same function. This could explain the adaptation of urban adapter species in various environments, including urban settings. We can therefore assume that there are feedback loops between the gut microbiota and the host species within communities, enabling rapid and flexible adaptation.
THE STRUCTURE OF DNA IN ANABIOTIC AND MUMMIFIED CELLS
Authors: Krupyanskii Yurii F. , Kovalenko Vladislav , Loiko Nataliya , Tereshkin Eduard , Tereshkina Ksenia , Popov Alexander 
Published: September 2023

AbstractInvestigations of structural organization of DNA for stressed (increased stress resistance), anabiotic and mummified cells obtained by introducing 4-hexylresorcinol at different concentrations for different stages of cell culture growth using diffraction of synchrotron radiation were done. Experimental studies allow us to conclude that 4-hexylresorcinol is the initiator of the cell transition to the anabiotic and mummified states at stationary state. At pre-stationary state of growth 4-hexylresorcinol initiates a transition of cells to a mummified state but not to anabiotic one. The structure of DNA within a cell in the anabiotic dormant state (practically complete absence of metabolism) and the dormant state (starvation stress) coincide (formsnanocrystallinestructures). Our data suggest the universality of DNA condensation or the universality of DNA protection by a protein Dps for dormant state, regardless of the type of stress. Mummified state (the complete absence of metabolism) is very different in structure (has no ordering within a cell).
Light at night and modeled circadian disruption predict higher risk of mortality: A prospective study in >88,000 participants
Authors: Windred Daniel P. , Burns Angus C. , Lane Jacqueline M. , Olivier Patrick , Rutter Martin K. , Saxena Richa , Phillips Andrew J. K. , Cain Sean W. 
Published: September 2023

AbstractImportanceLight at night disrupts human circadian rhythms, which are critical for maintaining optimal health. Circadian disruption accompanies poor health outcomes that precede premature mortality, including cardiometabolic diseases. However, links between personal night light exposure and premature mortality risk have not been established.ObjectiveTo characterize the association of light at night with all-cause and cardiometabolic mortality risks and to understand the role of circadian disruption in these associations by applying a computational model of the response of the human circadian pacemaker to light.DesignProspective cohort study.SettingUnited Kingdom.ParticipantsUK Biobank cohort, N=88,904, aged 62.4±7.8 years, 57% female.ExposureParticipants wore activity tracking watches with light sensors for one week between 2013-2016. Twenty-four-hour light exposure profiles were extracted for each participant, and day-time and night-time hours were defined by factor analysis. A validated mathematical model of the human circadian pacemaker was applied to model circadian amplitude and phase from weekly light data.Main OutcomeCause-specific mortality (National Health Service) recorded in 2,605 participants across a mean (±SD) follow-up period of 6.31±0.83 years after light/activity tracking.ResultsRisk of all-cause mortality was higher in participants in the 90th-100thpercentiles of night-light exposure (HR[95%CI]=1.30[1.15-1.48]), and for those between the 70th-90thpercentiles (HR=1.16[1.04-1.28]), compared to the darkest 50%. Participants in the 90th-100thpercentiles of night-light exposure also had higher risk of cardiometabolic mortality (HR=1.41[1.07-1.85]). Higher circadian amplitude predicted lower risks of all-cause mortality (HR = 0.94[0.91-0.97] per SD) and cardiometabolic mortality (HR=0.90[0.83-0.96]), and circadian phase that deviated from the group average predicted higher risks of all-cause mortality (HR=1.33[1.17-1.51]) and cardiometabolic mortality (HR=1.48[1.12-1.97]). These findings were robust to adjustment for age, sex, ethnicity, and sociodemographic and lifestyle factors.Conclusions and RelevanceMinimizing exposure to light at night and keeping regular light-dark patterns that enhance circadian rhythms may promote cardiometabolic health and longevity.Key PointsQuestionIs light exposure at night associated with risk of premature mortality?FindingsExposure to brighter light at night, recorded with personal light sensors in >88,000 participants, was associated with higher risk of mortality across a subsequent 6-year period. Computational modeling indicated that disrupted circadian rhythms may explain this higher mortality risk.MeaningAvoiding light at night may be a cost-effective and accessible recommendation for promoting health and longevity.
Cellular protein painting for structural and binding sites analysis via lysine reactivity profiling with o-phthalaldehyde
Authors: Zheng Zhenxiang , Zeng Ya , Lai Kunjia , Liao Bin , Li Pengfei , Tan Chris Soon Heng 
Published: September 2023

AbstractThe three-dimensional structure and the molecular interaction of proteins determine their roles in many cellular processes. Chemical protein painting with protein mass spectrometry can identify changes in structural conformations and molecular interactions of proteins including their binding sites. Nevertheless, most current protein painting techniques identified protein targets and binding sites of drugsin vitrousing cell lysate or purified protein. Here, we screened 11 membrane-permeable lysine-reactive chemical probes for intracellular covalent labeling of endogenous proteins, which revealsortho-phthalaldehyde (OPA) as the most reactive probe in intracellular environment. An MS workflow was developed and coupled with a new data analysis strategy termed RAPID (Reactive Amino acid Profiling by Inverse Detection) to enhance detection sensitivity. RAPID-OPA successfully identified structural change induced by allosteric drug TEPP-46 on its target protein PKM2, and was applied to profile conformation change of the proteome occurring in cells during thermal denaturation. Application of RAPID-OPA on cells treated with geldanamycin, selumetinib, and staurosporine successfully revealed their binding sites on target proteins. Thus, RAPID-OPA for cellular protein painting permits the identification of ligand-binding sites and detection of protein structural changes occurring in cells.Significance StatementProtein painting can be used to identify changes in the three-dimensional structure and molecular interaction of proteins that govern many cellular processes but are mostly applied to cell lysate or purified protein. We identified lysine reactive probes for the intracellular labeling of endogenous proteins, and developed an MS procedure with new data analysis strategy termed RAPID-OPA to characterize the intracellular conformation change of the proteome during thermal denaturation, and identified structural change mediated by allosteric regulator TEPP-46 on target protein PKM2. Furthermore, the approach could identify ligand binding sites exemplified by labeling of target proteins in cells treated with geldanamycin, selumetinib and staurosporine. Overall, RAPID-OPA for cellular protein painting enables the detection of protein structural changes happening in cells as well as the identification of ligand-binding sites.
Grey Mouse Lemurs’ response to acute caloric restriction before reproduction supports the “Thrifty Female Hypothesis”
Authors: Noiret Aude , Aujard Fabienne , Terrien Jeremy 
Published: September 2023

SummaryThe thrifty female hypothesis states that females would preserve more of their energy reserves during winter than males, because of a sex specific time-frame of energy allocation to reproduction. As males reactivate their reproductive axis before the mating period, while females mainly allocate energy in gestation and lactation, we make the hypothesis that males would have to use shorter torpor bouts and longer periods of normothermic activity in order to promote spermatogenesis during winter, a period of low food availability. Here we applied an acute two-week 80%CR in males and females grey mouse lemurs, shortly before the mating period. We show evidence of thriftier phenotypes in wintering females, which performed deeper and longer torpor bouts than males, and ultimately lost less body mass. Our results thus support the thrifty female hypothesis in a seasonally breeding primate, and reinforce the concept of a sex-biased trade-off in using torpor, which might ultimately benefit to reproduction and survival.
Improved estimation of molecular evolution coupling stochastic simulations and deep learning
Authors: Silvestro Daniele , Latrille Thibault , Salamin Nicolas 
Published: September 2023

AbstractModels have always been central to inferring molecular evolution and to reconstructing phylogenetic trees. Their use typically involves the development of a mechanistic framework reflecting our understanding of the underlying biological processes, such as nucleotide substitutions, and the estimation of model parameters by maximum likelihood or Bayesian inference. However, deriving and optimizing the likelihood of the data is not always possible under complex evolutionary scenarios or tractable for large datasets, often leading to unrealistic simplifying assumptions in the fitted models. To overcome this issue, we couple stochastic simulations of genome evolution with a new supervised deep learning model to infer key parameters of molecular evolution. Our model is designed to directly analyze multiple sequence alignments and estimate per-site evolutionary rates and divergence, without requiring a known phylogenetic tree. The accuracy of our predictions matches that of likelihood-based phylogenetic inference, when rate heterogeneity follows a simple gamma distribution, but it strongly exceeds it under more complex patterns of rate variation, such as codon models. Our approach is highly scalable and can be efficiently applied to genomic data, as we show on a dataset of 26 million nucleotides from the clownfish clade. Our simulations also show that the per-site rates obtained by deep learning increase the likelihood of the true tree and could therefore lead to more accurate phylogenetic inference. We propose that future advancements in phylogenetic analysis will benefit from a semi-supervised learning approach that combines deep-learning estimation of substitution rates, which allows for more flexible models of rate variation, and probabilistic inference of the phylogenetic tree, which guarantees interpretability and a rigorous assessments of statistical support.
Identity performances on professional accounting association magazine covers
Authors: Neal Anne K.H. , Bujaki Merridee Lynne , Durocher Sylvain , Brouard François 
Published: September 2023

PurposeThe authors examine and compare accounting associations' identities in distinct segments of the accounting profession surrounding the 2014 merger of three Canadian accounting associations.Design/methodology/approachThe authors conceive of accounting associations' magazine front covers as a setting for “identity performance” (i.e. a scenery through which identity dimensions are intentionally communicated to target audiences). The authors examine pre-merger and post-merger associations' identity performances that took place between January 2011 and December 2020 and identify 21 broad themes that the authors interpret in terms of identity logics (i.e. professionalism/commercialism) and audience focus (society/association members), underscoring (dis)similarities in identity performances pre- and post-merger.FindingsThe authors' analysis reveals distinct identity performances for the different segments of the pre-merger accounting profession and for the post-merger unified accounting association. Identity logics manifest differently: a commercial logic dominated for two of the associations and a professional logic dominated for the third. Identity fluidity was evident in the merged association's shift from commercial toward professional logic when the association ceased publishing one magazine and introduced a new one. Society rather than associations' members dominated as a target audience for all associations, but this focus manifested differently. Post-merger, identity performances continued to focus on society as the audience.Originality/valueThe authors highlight the Goffmanian identity performances (Goffman, 1959) taking place via accounting associations' magazines. The authors adopt a segment perspective (Bucher and Strauss, 1961) that demonstrates that commercialism does not trump professionalism in all segments of the profession. For the first time, the authors juxtapose identity logics (professionalism/commercialism) and targeted audiences to better understand how these facets of accountants' identities compare between segments.