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Electro-driven direct lithium extraction from geothermal brines to generate battery-grade lithium hydroxide
Association between herpes simplex virus infection and Alzheimer’s disease biomarkers: analysis within the MAPT trial
Abstract In vitro and animal studies have suggested that inoculation with herpes simplex virus 1 (HSV-1) can lead to amyloid deposits, hyperphosphorylation of tau, and/or neuronal loss. Here, we studied the association between HSV-1 and Alzheimer’s disease biomarkers in humans. Our sample included 182 participants at risk of cognitive decline from the Multidomain Alzheimer Preventive Trial who had HSV-1 plasma serology and an amyloid PET scan. Plasma Aβ42/40 ratio, neurofilament light chain and p-tau181 were also available for a sub-sample of participants. Multivariate linear regressions were performed and stratified by APOE4 genotype. The median age was 74.0 years, 85.2% were infected with HSV-1. Infected participants tended to have a lower cortical amyloid load than uninfected participants (β = -0.08, p = 0.06), especially those suspected of reactivating HSV-1 most frequently (i.e. with a high anti-HSV-1 IgG level; n = 58, β = -0.09 p = 0.04). After stratification, the association was only significant in APOE4 carriers (n = 43, β = -0.21 p = 0.01). No association was found with the plasma biomarkers. The trend toward lower cortical amyloid load in HSV-1-infected participants was unexpected given the pre-existing literature and may be explained either by a modified immune response in HSV-1 infected subjects which could favour the clearance of amyloid deposits or by a selection bias.
The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis
Abstract The development of granulomas with central necrosis harboring Mycobacterium tuberculosis (Mtb) is the hallmark of human tuberculosis (TB). New anti-TB therapies need to effectively penetrate the cellular and necrotic compartments of these lesions and reach sufficient concentrations to eliminate Mtb. BTZ-043 is a novel antibiotic showing good bactericidal activity in humans in a phase IIa trial. Here, we report on lesional BTZ-043 concentrations severalfold above the minimal-inhibitory-concentration and the substantial local efficacy of BTZ-043 in interleukin-13-overexpressing mice, which mimic human TB pathology of granuloma necrosis. High-resolution MALDI imaging further reveals that BTZ-043 diffuses and accumulates in the cellular compartment, and fully penetrates the necrotic center. This is the first study that visualizes an efficient penetration and accumulation of a clinical-stage TB drug in human-like centrally necrotizing granulomas and that also determines its lesional activity. Our results most likely predict a substantial bactericidal effect of BTZ-043 at these hard-to-reach sites in TB patients.
A modelling technique to determine the high frequency transformer leakage inductance using the winding structure
Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics
A slab window in the south rim of the Parece-Vela Basin
Abstract Slab windows represent regions within the mantle that are largely devoid of slab material, facilitating direct communication between the mantle above and below the subducting slab. This unprecedented interaction disrupts the conventional material-energy exchange mechanisms between the subducted slab and mantle wedge, giving rise to anomalous heat flow, distinct magmatism, metamorphism, and geophysical features. Geochemical analyses of samples collected from the southern margin of the Parece-Vela Basin have illuminated the magmatic processes associated with a slab window. C20-3 is indicative of a hot and dry mantle upwelling that occurs through the slab window. On the other hand, C20-1 signifies an adakitic rock, which originates from the melting of oceanic crust at the periphery of the slab window. Slightly east of the slab window, C21-1 reveals evidence of a heated depleted mantle, influenced by the hot and dry mantle upwelling through the slab window. Additionally, a common Island Arc Basalt (IAB), denoted as C21-2, was also observed in the island arc region. Topographical data highlights the irregular distribution of numerous seamounts between the West Mariana Ridge and the Parece-Vela Basin spreading center. Seismological records reveal a preponderance of strike-slip earthquakes in the southern seamount region, alongside exceptionally high heat flow measurements at the northwest extremity of this area. The shape of the slab window can be roughly modeled by analyzing the distribution of earthquakes. Collectively, these observations lead us to postulate the existence of a slab window beneath the southern rim of the Parece-Vela Basin, likely attributed to the tearing of the subducting Pacific Plate along the strike-slip fault situated between the Ulithi and Fais Atolls.
Optical signatures of lattice strain in chemically doped colloidal quantum wells
Steroid hormone receptors, exome sequencing and treatment responsiveness of breast cancer patient-derived xenografts originated in a South American country
Decoding the m6A epitranscriptomic landscape for biotechnological applications using a direct RNA sequencing approach
Abstract Epitranscriptomic modifications, particularly N6-methyladenosine (m6A), are crucial regulators of gene expression, influencing processes such as RNA stability, splicing, and translation. Traditional computational methods for detecting m6A from Nanopore direct RNA sequencing (DRS) data are constrained by their reliance on experimentally validated labels, often resulting in the underestimation of modification sites. Here, we introduce pum6a, an innovative attention-based framework that integrates positive and unlabeled multi-instance learning (MIL) to address the challenges of incomplete labeling and missing read-level annotations. By combining electrical signal features with base alignment data and employing a weighted Noisy-OR probability mechanism, pum6a achieves enhanced sensitivity and accuracy in m6A detection, particularly in low-coverage loci. Pum6a outperforms existing methods in identifying m6A sites across various cell lines and species, without requiring extensive parameter tuning. We further apply pum6a to study the dynamic regulation of m6A demethylases in gastric cancer under hypoxia, revealing distinct roles for FTO and ALKBH5 in modulating m6A modifications and uncovering key insights into m6A -mediated transcript stability. Our findings highlight the potential of pum6a as a powerful tool for advancing the understanding of epitranscriptomic regulation in health and disease, paving the way for biotechnological and therapeutic applications.
Formulation and characterization of surfactants with antibacterial and corrosion-inhibiting properties for enhancing shale gas drainage and production
Mass wasting reveals ongoing asymmetric retreat of the martian north polar ice cap
Abstract Ongoing mass wasting through ice block falls is intensive at the north polar ice cap of Mars. We monitored how this activity is currently shaping the marginal steep scarps of the ice cap, which holds a record of the planet’s climate history. With AI-driven change detection between multi-temporal high-resolution satellite images, we created a comprehensive map of mass wasting across the entire North Polar Layered Deposits (NPLD). Our results show a more active erosion process than previously thought, with scarps retreating by up to ~3 m every kiloyear. The distribution of the active scarps indicates an ongoing asymmetric retreat of the already subcircular ice cap. The active scarps and the interior dune fields correlate strongly with exposures of the underlying, sandier Basal Unit (BU), providing evidence that erosion of the BU undermines the base of the NPLD. Moreover, ice block fall activity suggests potential areas where gypsum is released, given that the interior gypsum-bearing dune fields are located adjacent to these active scarps. Here, our study reveals the rates of present-day topographic change of the north polar ice cap, providing a valuable constraint for study of its past evolution.
Prognostic significance of right subdiaphragmatic washing cytology in patients with endometrial cancer
Life-history adaptation under climate warming magnifies the agricultural footprint of a cosmopolitan insect pest
Abstract Climate change is affecting population growth rates of ectothermic pests with potentially dire consequences for agriculture and global food security. However, current projection models of pest impact typically overlook the potential for rapid genetic adaptation, making current forecasts uncertain. Here, we predict how climate change adaptation in life-history traits of insect pests affects their growth rates and impact on agricultural yields by unifying thermodynamics with classic theory on resource acquisition and allocation trade-offs between foraging, reproduction, and maintenance. Our model predicts that warming temperatures will favour resource allocation towards maintenance coupled with increased resource acquisition through larval foraging, and the evolution of this life-history strategy results in both increased population growth rates and per capita host consumption, causing a double-blow on agricultural yields. We find support for these predictions by studying thermal adaptation in life-history traits and gene expression in the wide-spread insect pest, Callosobruchus maculatus ; with 5 years of evolution under experimental warming causing an almost two-fold increase in its predicted agricultural footprint. These results show that pest adaptation can offset current projections of agricultural impact and emphasize the need for integrating a mechanistic understanding of life-history evolution into forecasts of pest impact under climate change.
Insights into spinetail devil ray spatial ecology in the Mediterranean Sea through satellite telemetry
Non-metallic iodine single-atom catalysts with optimized electronic structures for efficient Fenton-like reactions
Crayfish optimization based pixel selection using block scrambling based encryption for secure cloud computing environment
Reverse mutational scanning of SARS-CoV-2 spike BA.2.86 identifies epitopes contributing to immune escape from polyclonal sera
Abstract The recently detected Omicron BA.2.86 lineage contains more than 30 amino acid mutations relative to BA.2. BA.2.86 and its JN.1 derivative evade neutralization by serum antibodies of fully vaccinated individuals. In this study, we elucidate epitopes driving the immune escape of BA.2.86 and JN.1 via pseudovirus neutralization. Here we generate 33 BA.2.86 mutants, each reverting a single mutation back to BA.2. We use this library in an approach that we call reverse mutational scanning to define distinct neutralization titers against each epitope. Mutations within the receptor binding domain at K356T, V483Δ, and to a lesser extent N460K, A484K, and F486P enhance immune escape. Interestingly, 16insMPLF within the spike N-terminal domain and P621S within S1/S2 also significantly contribute to antibody escape of BA.2.86. Upon XBB.1.5 booster vaccination, neutralization titers against JN.1 and BA.2.86 improve considerably, and residual immune escape is driven by 16insMPLF, N460K, E554K, and to a lesser extent P621S, and A484K.
Accelerometric assessment of fatigue-induced changes in swimming technique in high performance adolescent athletes
Abstract The present study analyzed the kinematic changes under fatigue in highly trained adolescent swimmers during a 50-m all-out front cwal test. Twenty-four girls and fourteen boys aged 12–13 participated in the study. The movement of the hip rim was analyzed using a specialized inertial device equipped with a triaxial gyroscope and accelerometer to measure changes in angular velocity and acceleration. Between the first and second lengths of the pool, the following were observed: a significant (F1.36 = 63.6; p < 0.0001; η 2 = 0.64) increase (34%) in maximum pelvic angle, significant (F1,36 = 6.0; p = 0.0193; η 2 = 0.14;) increase (12.10%) in angular velocity in rotational motion around a vertical axis, and a significant (F1,36 = 11.29; p = 0.0018; η 2 = 0.24) increase (6.86%) in angular velocity in yaw rotation motion around the sagittal axis. Significant (F1,36 = 13.96; p = 0.0006; η 2 = 0.28) differences in maximum pelvic angle were observed for lap and side. As unfavourable changes in kinematics are already observed in the second half of the distance, it is therefore suspected that performing frequent high-intensity repetitions may lead to the perpetuation of unfavourable movement patterns. Taking this into account, coaches should limit maximum-speed swimming in adolescent athletes to short distances and an appropriate interval and use training methods to reduce asymmetric work such as training snorkels.