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A Human IgE Antibody Binding Site on Der p 2 for the Design of a Recombinant Allergen for Immunotherapy

Der p 2 is one of the most important allergens from the house dust mite Dermatophagoides pteronyssinus Identification of human IgE Ab binding epitopes can be used for rational design of allergens with reduced IgE reactivity for therapy. Antigenic analysis of Der p 2 was performed by site-directed mutagenesis based on the x-ray crystal structure of the allergen in complex with a Fab from the murine

Galectin-1 induces a tumor-associated macrophage phenotype and upregulates indoleamine 2,3-dioxygenase-1

Galectins are a group of carbohydrate-binding proteins with a presumed immunomodulatory role and an elusive function on antigen-presenting cells. Here we analyzed the expression of galectin-1 and found upregulation of galectin-1 in the extracellular matrix across multiple tumors. Performing an in-depth and dynamic proteomic and phosphoproteomic analysis of human macrophages stimulated with galecti

Identification of pathogenic GCK variants in patients with common type 2 diabetes can lead to discontinuation of pharmacological treatment

Background: Functionally disruptive variants in the glucokinase gene (GCK) cause a form of mild non-progressive hyperglycemia, which does not require pharmacological treatment. A substantial proportion of patients with type 2 diabetes (T2D) carry GCK variants. We aimed to investigate whether carriers of rare GCK variants diagnosed with T2D have a glycemic phenotype and treatment response consisten

Adaptive Filter Models

The original chapter on adaptive-filter models addressed the issue of how far such models were consistent with experimental evidence. Here we consider one particularly important kind of evidence, that concerning the nature of the synaptic plasticity that underlies cerebellar learning. The basic decorrelation learning rule employed by the adaptive-filter model can be translated into spike timing-de

The effects of sea-state on optimal generator parameters for a wave energy converter

The power take-off (PTO) system and control laws for wave energy converters (WECs) are crucial for system performance. Determining optimal PTO parameters based on different sea states is key for formulating control laws, identifying optimal WEC locations, and optimizing wave-to-wire performance. This study focuses on an oscillating water column (OWC) type WEC developed by Waves4Power using a buoy

Exogenous estrogen enhances T cell activation in male primates

Estrogen influences T cell development and enhances infection resistance in females, but its immunological effects during gender-affirming hormone therapy (GAHT) remain poorly understood. Here, we characterize immune adaptations in male rhesus macaques (RMs) treated with 17β-estradiol (E2) or placebo over 7 months. E2 therapy suppressed endogenous testosterone production, induced female physical t

T cell responses towards PINK1 and α-synuclein are elevated in prodromal Parkinson’s disease

A role of the immune system in Parkinson’s disease (PD) progression has long been suspected due to the increased frequency of activated glial cells and infiltrating T cells in the substantia nigra. It was previously reported that PD donors have increased T cell responses towards PINK1 and α-synuclein (α-syn), two Lewy body-associated proteins. Further, T cell reactivity towards α-syn was highest c

Time-lagged genomic erosion and future environmental risks in a bird on the brink of extinction

Global biodiversity is rapidly declining due to habitat degradation and genomic erosion, highlighting the urgent need to monitor endangered species and their genetic health. Temporal genomics and ecological modelling offer finer resolution than single-Time-point measurements, providing a comprehensive view of species' recent and future trajectories. We investigated genomic erosion and environmenta

CKD-EPI and EKFC GFR Estimating Equations: Performance and Other Considerations for Selecting Equations for Implementation in Adults

Background: New CKD-EPI and EKFC estimated GFR (eGFR) equations usingcreatinine (eGFRcr), cystatin C (eGFRcys) and both (eGFRcr-cys) have sufficientaccuracy for use in clinical practice. A better understanding of the equations, includingtheir performance in race, sex and age subgroups, is important for selection of eGFRequations for global implementation.Methods: We evaluated performance (bias and

Interferon Alpha-Inducible Protein 27 Expression Is Linked to Disease Severity in Chronic Infection of Both HIV-1 and HIV-2

Disease progression is slower in HIV-2, as compared with HIV-1 infection, in accordance with low or undetectable plasma viremia at viral setpoint. However, it is unclear why most HIV-2 infected individuals are still at risk of developing AIDS. To explore if specific host responses are linked to HIV disease severity, we have compared blood gene expression profiles between HIV seronegative and HIV-1

Twenty‐Four‐Hour Ambulatory Blood Pressure Profile in Patients With Reflex Syncope and Matched Controls

BackgroundAmbulatory blood pressure (BP) monitoring has long been used to monitor BP in hypertension and lately emerged as a useful tool to detect hypotensive susceptibility in reflex syncope. However, hemodynamic characteristics in reflex syncope have not been sufficiently explored. The present study investigated the differences between ambulatory BP monitoring profiles associated with reflex syn

Establishing conversion of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly scores into interval-level data across multiple samples using Rasch methodology

Background: The 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) is a well-validated and widely-used measure of cognitive changes (CCs) among older adults. This study aimed to use Rasch methodology to establish psychometric properties of the IQCODE-16 and validate the existing ordinal-to-interval transformation algorithms across multiple large samples. Methods: A Par

Improved distances and ages for stars common to TGAS and RAVE

We combine parallaxes from the first Gaia data release with the spectrophotometric distance estimation framework for stars in the fifth RAVE survey data release. The combined distance estimates aremore accurate than either determination in isolation - uncertainties are on average two times smaller than for RAVE-only distances (three times smaller for dwarfs), and 1.4 times smaller than TGAS parall

Severe Congenital Thrombocytopenia Characterized by Decreased Platelet Sialylation and Moderate Complement Activation Caused by Novel Compound Heterozygous Variants in GNE

Background: Hereditary thrombocytopenias constitute a genetically heterogeneouscause of increased bleeding. We report a case of a 17-year-old boy suffering fromsevere macrothrombocytopenia throughout his life. Whole genome sequencing revealed the presence of two compound heterozygous variants in GNE encoding the enzyme UDP-N-acetyl-glucosamine-2-epimerase/N-acetylmannosamine kinase, crucial for si

Assembly of protein S and C4b-binding protein on membranes

The interaction of protein S with membranes and subsequent combination with complement C4b-binding protein (C4BP) was studied. Protein S interacted with phospholipid vesicles in a calcium-dependent manner typical of other vitamin K-dependent proteins. Association of C4BP with protein S showed no apparent selectivity for membrane-bound or solution phase protein S. When bound to the membrane, the pr

Analysis of Early Science observations with the CHaracterising ExOPlanets Satellite (CHEOPS) using pycheops

CHEOPS (CHaracterising ExOPlanet Satellite) is an ESA S-class mission that observes bright stars at high cadence from low-Earth orbit. The main aim of the mission is to characterize exoplanets that transit nearby stars using ultrahigh precision photometry. Here, we report the analysis of transits observed by CHEOPS during its Early Science observing programme for four well-known exoplanets: GJ 436

Novel methods of malignant brain tumor treatment utilizing the tumor microenvironment

Malignant brain tumors constitute a disaster in the lives of patients, either in the form of extremely low survival in glioblastoma, or the serious long-term adverse effects of therapy in medulloblastoma. These two tumor types represent the most common malignant brain entities in adults and children, respectively. Ever since the early 2000’s, no major improvement of patient outcomes occurred. Immu