Miracle-dz/UniFAR-FTUs huggingface dataset:
Climate change resilience of a globally important sea turtle nesting population

Few studies have looked into climate change resilience of populations of wild animals. We use a model higher vertebrate, the green sea turtle, as its life history is fundamentally affected by climatic conditions, including temperature‐dependent sex determination and obligate use of beaches subject to sea level rise (SLR). We use empirical data from a globally important population in West Africa to assess resistance to climate change within a quantitative framework. We project 200 years of primary sex ratios (1900–2100) and create a digital elevation model of the nesting beach to estimate impacts of projected SLR. Primary sex ratio is currently almost balanced, with 52% of hatchlings produced being female. Under IPCC models, we predict: (a) an increase in the proportion of females by 2100 to 76%–93%, but cooler temperatures, both at the end of the nesting season and in shaded areas, will guarantee male hatchling production; (b) IPCC SLR scenarios will lead to 33.4%–43.0% loss of the current nesting area; (c) climate change will contribute to population growth through population feminization, with 32%–64% more nesting females expected by 2120; (d) as incubation temperatures approach lethal levels, however, the population will cease growing and start to decline. Taken together with other factors (degree of foraging plasticity, rookery size and trajectory, and prevailing threats), this nesting population should resist climate change until 2100, and the availability of spatial and temporal microrefugia indicates potential for resilience to predicted impacts, through the evolution of nest site selection or changes in nesting phenology. This represents the most comprehensive assessment to date of climate change resilience of a marine reptile using the most up‐to‐date IPCC models, appraising the impacts of temperature and SLR, integrated with additional ecological and demographic parameters. We suggest this as a framework for other populations, species and taxa.
Early‐life telomere length predicts lifespan and lifetime reproductive success in a wild bird

Poor conditions during early development can initiate trade‐offs that favour current survival at the expense of somatic maintenance and subsequently, future reproduction. However, the mechanisms that link early and late life‐history are largely unknown. Recently it has been suggested that telomeres, the nucleoprotein structures at the terminal end of chromosomes, could link early‐life conditions to lifespan and fitness. In wild purple‐crowned fairy‐wrens, we combined measurements of nestling telomere length (TL) with detailed life‐history data to investigate whether early‐life TL predicts fitness prospects. Our study differs from previous studies in the completeness of our fitness estimates in a highly philopatric population. The association between TL and survival was age‐dependent with early‐life TL having a positive effect on lifespan only among individuals that survived their first year. Early‐life TL was not associated with the probability or age of gaining a breeding position. Interestingly, early‐life TL was positively related to breeding duration, contribution to population growth and lifetime reproductive success because of their association with lifespan. Thus, early‐life TL, which reflects growth, accumulated early‐life stress and inherited TL, predicted fitness in birds that reached adulthood but not noticeably among fledglings. These findings suggest that a lack of investment in somatic maintenance during development particularly affects late life performance. This study demonstrates that factors in early‐life are related to fitness prospects through lifespan, and suggests that the study of telomeres may provide insight into the underlying physiological mechanisms linking early‐ and late‐life performance and trade‐offs across a lifetime.
Fine-mapping cis-regulatory variants in diverse human populations

Genome-wide association studies (GWAS) are a powerful approach for connecting genotype to phenotype. Most GWAS hits are located in cis-regulatory regions, but the underlying causal variants and their molecular mechanisms remain unknown. To better understand human cis-regulatory variation, we mapped quantitative trait loci for chromatin accessibility (caQTLs)—a key step in cis-regulation—in 1000 individuals from 10 diverse populations. Most caQTLs were shared across populations, allowing us to leverage the genetic diversity to fine-map candidate causal regulatory variants, several thousand of which have been previously implicated in GWAS. In addition, many caQTLs that affect the expression of distal genes also alter the landscape of long-range chromosomal interactions, suggesting a mechanism for long-range expression QTLs. In sum, our results show that molecular QTL mapping integrated across diverse populations provides a high-resolution view of how worldwide human genetic variation affects chromatin accessibility, gene expression, and phenotype.
Comparison of Survival Prediction with Single versus Combination Use of Microcirculation End Point Resuscitation in Sepsis and Septic Shock.

BACKGROUND lactate clearance and central venous oxygen saturation (ScvO2) are two methods for determining tissue oxygenation adequacy. There is a controversy regarding method better associates with and predicts sepsis and septic shock patients' mortality. This study address the association of achieving one or two targets of microcirculatory resuscitation endpoints and early mortality in sepsis and septic shock. METHODS a cohort study was conducted in adult sepsis and septic shock patients in Intensive Care Unit, Cipto Mangunkusumo Hospital, Indonesia. Patients' resuscitation endpoints data and outcome were observed during the first 120 hours of hospitalization. Cox's proportional hazard regression analysis was used to analyse the early mortality risk in subject groups achieving lactate clearance target only, ScvO2 target only, both targets, and not achieving any target in 6 hours after onset of resuscitation adjusted for number of organ dysfunction. RESULTS subjects consisted of 268 patients. There were significant differences in the mortality risk between subjects who achieved both targets with subjects who achieved ScvO2 target only (adjusted hazard ratio [aHR] 13.47; 95% confidence interval [CI] 5.17-35.08) and subjects who not achieve any target (aHR 16.12; 95%CI 7.43-34.95). There were insignificant difference the early mortality risk between subjects who achieved both targets with subjects achieved lactate clearance target only (aHR 2.29; 95%CI 0.83-6.32). CONCLUSION in patients with sepsis and septic shock, achievement of lactate clearance and ScvO2 targets associates with similar early mortality risk compared to achievement of lactate clearance target only. However, it associates with lower early mortality risk compared with ScvO2 target only.
Chemically reprogramming the phospho‐transfer reaction to crosslink protein kinases to their substrates

The proteomic mapping of enzyme–substrate interactions is challenged by their transient nature. A method to capture interacting protein kinases in complexes with a single substrate of interest would provide a new tool for mapping kinase signaling networks. Here, we describe a nucleotide‐based substrate analog capable of reprogramming the wild‐type phosphoryl‐transfer reaction to produce a kinase‐acrylamide‐based thioether crosslink to mutant substrates with a cysteine nucleophile substituted at the native phosphorylation site. A previously reported ATP‐based methacrylate crosslinker (ATP‐MA) was capable of mediating kinase crosslinking to short peptides but not protein substrates. Exploration of structural variants of ATP‐MA to enable crosslinking of protein substrates to kinases led to the discovery that an ADP‐based methacrylate (ADP‐MA) crosslinker was superior to the ATP scaffold at crosslinking in vitro. The improved efficiency of ADP‐MA over ATP‐MA is due to reduced inhibition of the second step of the kinase–substrate crosslinking reaction by the product of the first step of the reaction. The new probe, ADP‐MA, demonstrated enhanced in vitro crosslinking between the Src tyrosine kinase and its substrate Cortactin in a phosphorylation site‐specific manner. The kinase–substrate crosslinking reaction can be carried out in a complex mammalian cell lysate setting, although the low abundance of endogenous kinases remains a significant challenge for efficient capture.
microRNA‐26a‐5p affects myocardial injury induced by coronary microembolization by modulating HMGA1

Coronary microembolization (CME) occurs when atherosclerotic plaque debris is detached during the treatment of acute coronary syndrome with Percutaneous Coronary Intervention (PCI). The complications of distal microvascular embolism, including local myocardial inflammation, are the main causes of myocardial damage and are a strong predictor of poor long‐term prognosis and major cardiac adverse events. microRNAs (miRNAs) are involved in the pathophysiological processes of cardiovascular inflammatory diseases. Dysregulation of microRNA (miR)‐26a‐5p, in particular, is associated with a variety of cardiovascular diseases. However, the role of miR‐26a‐5p in CME‐induced myocardial injury is unclear. In this study, we developed an animal model of CME by injecting microembolic balls into the left ventricle of rats and found that miR‐26a‐5p expression decreased in myocardial tissue in response. Using a miR‐26a‐5p mimic, echocardiography, hematoxylin‐eosin staining, and Western blot analysis we found that the diminished cardiac function and myocardial inflammation induced by CME is alleviated by miR‐26a‐5p overexpression. Furthermore, our results show that inhibitors of miR‐26a‐5p have the opposite effect. In addition, in vitro experiments using real‐time PCR, Western blot analysis, and a dual luciferase reporter gene show that HMGA1 is a target gene of miR‐26a‐5p. Thus, overexpression of miR‐26a‐5p could be a novel therapy to improve CME‐induced myocardial damage.
Microbes drive global soil nitrogen mineralization and availability

Soil net nitrogen mineralization rate (Nmin), which is critical for soil nitrogen availability and plant growth, is thought to be primarily controlled by climate and soil physical and/or chemical properties. However, the role of microbes on regulating soil Nmin has not been evaluated on the global scale. By compiling 1565 observational data points of potential net Nmin from 198 published studies across terrestrial ecosystems, we found that Nmin significantly increased with soil microbial biomass, total nitrogen, and mean annual precipitation, but decreased with soil pH. The variation of Nmin was ascribed predominantly to soil microbial biomass on global and biome scales. Mean annual precipitation, soil pH, and total soil nitrogen significantly influenced Nmin through soil microbes. The structural equation models (SEM) showed that soil substrates were the main factors controlling Nmin when microbial biomass was excluded. Microbe became the primary driver when it was included in SEM analysis. SEM with soil microbial biomass improved the Nmin prediction by 19% in comparison with that devoid of soil microbial biomass. The changes in Nmin contributed the most to global soil NH4+‐N variations in contrast to climate and soil properties. This study reveals the complex interactions of climate, soil properties, and microbes on Nmin and highlights the importance of soil microbial biomass in determining Nmin and nitrogen availability across the globe. The findings necessitate accurate representation of microbes in Earth system models to better predict nitrogen cycle under global change.
Multiomics resolution of molecular events during a day in the life of Chlamydomonas

Significance Chlamydomonas reinhardtii is the premier reference organism for understanding unicellular green algae. Chlamydomonas is an important model for photosynthesis as well as fermentation and other anaerobic pathways under dark anoxic conditions. We have produced a diurnal transcriptome, validated by subproteomic analyses, and matched with measurements of pigments, select metabolites, and physiological parameters. We report that the majority of the algal genome is differentially expressed over the course of the day and the timing of specific genes is dictated by their biological function. We also discovered that fermentation rather than respiration is the preferred metabolic fate of starch-derived glycolytic pyruvate. We offer our rich dataset to the algal and plant communities. The unicellular green alga Chlamydomonas reinhardtii displays metabolic flexibility in response to a changing environment. We analyzed expression patterns of its three genomes in cells grown under light–dark cycles. Nearly 85% of transcribed genes show differential expression, with different sets of transcripts being up-regulated over the course of the day to coordinate cellular growth before undergoing cell division. Parallel measurements of select metabolites and pigments, physiological parameters, and a subset of proteins allow us to infer metabolic events and to evaluate the impact of the transcriptome on the proteome. Among the findings are the observations that Chlamydomonas exhibits lower respiratory activity at night compared with the day; multiple fermentation pathways, some oxygen-sensitive, are expressed at night in aerated cultures; we propose that the ferredoxin, FDX9, is potentially the electron donor to hydrogenases. The light stress-responsive genes PSBS, LHCSR1, and LHCSR3 show an acute response to lights-on at dawn under abrupt dark-to-light transitions, while LHCSR3 genes also exhibit a later, second burst in expression in the middle of the day dependent on light intensity. Each response to light (acute and sustained) can be selectively activated under specific conditions. Our expression dataset, complemented with coexpression networks and metabolite profiling, should constitute an excellent resource for the algal and plant communities.
Apolipoprotein A1 Forms 5/5 and 5/4 Antiparallel Dimers in Human High-density Lipoprotein*

The structural orientation of apolipoprotein A1 (APOA1) dimers in reconstituted high-density lipoprotein (HDL) and human HDL was determined by zero-length chemical cross-linking and MS/MS analysis. The peptide cross-links provide strong biochemical evidence of the LL5/5 and LL5/4 antiparallel APOA1 dimers in human HDL and are in excellent agreement with molecular modeling. We validated our findings using synthetic cross-linked peptides. Our observations indicate that phospholipidated APOA1 forms two distinct antiparallel dimers that likely bind different proteins with important functional consequences. Graphical Abstract Highlights Zero-length chemical cross-linking of APOA1 peptides in HDL. Cross-links match antiparallel isomers of APOA dimers in molecular modeling. Identical MS/MS spectra of native and synthetic cross-linked peptides. First biochemical evidence of LL5/5 and LL5/4 isomers in human HDL. Apolipoprotein A1 (APOA1), the major protein of high-density lipoprotein (HDL), contains 10 helical repeats that play key roles in protein-protein and protein-lipid interactions. The current structural model for HDL proposes that APOA1 forms an antiparallel dimer in which helix 5 in monomer 1 associates with helix 5 in monomer 2 along a left-left (LL5/5) interface, forming a protein complex with a 2-fold axis of symmetry centered on helix 5. However, computational studies suggest that other orientations are possible. To test this idea, we used a zero-length chemical cross-linking reagent that forms covalent bonds between closely apposed basic and acidic residues. Using proteolytic digestion and tandem mass spectrometry, we identified amino acids in the central region of the antiparallel APOA1 dimer of HDL that were in close contact. As predicted by the current model, we found six intermolecular cross-links that were consistent with the antiparallel LL5/5 registry. However, we also identified three intermolecular cross-links that were consistent with the antiparallel LL5/4 registry. The LL5/5 is the major structural conformation of the two complexes in both reconstituted discoidal HDL particles and in spherical HDL from human plasma. Molecular dynamic simulations suggest that that LL5/5 and LL5/4 APOA1 dimers possess similar free energies of dimerization, with LL5/5 having the lowest free energy. Our observations indicate that phospholipidated APOA1 in HDL forms different antiparallel dimers that could play distinct roles in enzyme regulation, assembly of specific protein complexes, and the functional properties of HDL in humans.
Planification interactive de mouvement avec contact

La conception de nouveaux produits industriels necessite le developpement de prototypes avant leur deploiement grand public. Afin d'accelerer cette phase et de reduire les couts qui en decoulent, une solution interessante consiste a utiliser des prototypes virtuels le plus longtemps possible en particulier dans la phase de conception. Certaines des etapes de la conception consistent a effectuer des operations d'assemblage ou de desassemblage. Ces operations peuvent etre effectuees manuellement ou automatiquement a l'aide d'un algorithme de planification de mouvement. La planification de mouvement est une methode permettant a un ordinateur de simuler le deplacement d'un objet d'un point de depart a un point d'arrivee tout en evitant les obstacles. Le travail de recherche de cette these apporte des solutions pour l'interaction entre un humain et un algorithme de planification de mouvement pendant l'exploration de l'espace libre. Le temps de recherche est partage entre l'humain et la machine selon un parametre de partage d'autorite permettant de determiner le pourcentage d'allocation du temps a l'une ou l'autre entite. L'utilisation de ces deux entites en meme temps permet d'accelerer grandement la vitesse d'exploration par rapport a la vitesse d'un humain seul ou d'un algorithme seul. Ces travaux apportent ensuite une nouvelle methode de planification de mouvement avec contact permettant de generer des trajectoires a la surface des obstacles au lieu de les generer uniquement dans l'espace libre. La planification au contact permet d'effectuer des operations specifiques telles que le glissement ou l'insertion utiles pour la resolution de problemes de planification dans des environnements encombres. Enfin, detecter les intentions d'un utilisateur lorsqu'il interagit avec une m achine permet de lui fournir des ordres efficacement et intuitivement. Dans le cadre de la planification interactive au contact, un algorithme de detection d'intention est propose. Ce dernier s'appuie sur l'utilisation d'un robot haptique permettant a un operateur de ressentir les obstacles virtuels lors de la manipulation d'un objet virtuel dans un environnement de realite virtuelle. L'algorithme interactif s'adapte en temps reel aux actions de l'operateur pour une exploration pertinente de la surface des obstacles. Ces travaux ont ete menes en partie au laboratoire toulousain LAAS au sein de l'equipe Gepetto et en partie dans le laboratoire LGP de l'ENIT au sein de l'equipe DIDS. Nous remercions la region Midi-Pyrenees pour avoir finance ces recherches.
Overall Survival of Black and White Men With Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel.

PURPOSE Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen. METHODS Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). RESULTS Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001). CONCLUSION When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.
A Cross-Sectional Description of Parental Perceptions and Practices Related to Risky Play and Independent Mobility in Children: The New Zealand State of Play Survey

The potential for risky play and independent mobility to increase children’s physical activity, and enhance cognitive development and emotional wellbeing has been recognised for some time. The aim of this study was to describe the attitudes of New Zealand parents towards such risky play practices and independent mobility, the barriers preventing them from allowing their children to participate, and how often their children engaged in risky play activities. An online survey comprised mostly of validated scales and standardised questions was completed by a nationally representative sample of 2003 parents. We found that parents had neutral feelings about the risk of injury to their child through play, rather they were concerned about road safety and “stranger danger”. There was strong agreement that there are multiple benefits to be gained from exposure to risk and challenge, and that health and safety rules are too strict. However, 73% of respondents stated that their 5–12 year old child seldom or never engaged in four or more risky activities, and only 14.3% engaged in four or more often or always. While parents agree that their child is likely to benefit from risky play, they do not have the confidence to allow their children to engage in such activities. Future research should address barriers and fears when implementing strategies to facilitate risky play.
Demonstration of Fin-Tunnel Field-Effect Transistor with Elevated Drain

In this paper, a novel tunnel field-effect transistor (TFET) has been demonstrated. The proposed TFET features a SiGe channel, a fin structure and an elevated drain to improve its electrical performance. As a result, it shows high-level ON-state current (ION) and low-level OFF-state current (IOFF); ambipolar current (IAMB). In detail, its ION is enhanced by 24 times more than that of Si control group and by 6 times more than of SiGe control group. The IAMB can be reduced by up to 900 times compared with the SiGe control group. In addition, technology computer-aided design (TCAD) simulation is performed to optimize electrical performance. Then, the benchmarking of ON/OFF current is also discussed with other research group’s results.