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A walk through tau therapeutic strategies

Tau neuronal and glial pathologies drive the clinical presentation of Alzheimer's disease and related human tauopathies. There is a growing body of evidence indicating that pathological tau species can travel from cell to cell and spread the pathology through the brain. Throughout the last decade, physiological and pathological tau have become attractive targets for AD therapies. Several therapeut

Roles of PDZ-dependent Interactions and N-glycosylation in G Protein-coupled Estrogen Receptor 1 (GPER1)/GPR30-mediated Stimulation of ERK1/2 Activity

G protein-coupled receptor 30 (GPR30) is a G protein-coupled receptor (GPCR) that is attracting considerable attention in breast cancer and cardiometabolic regulation. Following reports that GPR30 is required for some rapid estrogen responses, e.g. increased cAMP production and ERK1/2 activity, in estrogen receptor (ER)-negative cells, GPR30 was renamed G protein-coupled estrogen receptor 1 (GPER1

ETFAD/EADV Eczema task force 2015 position paper on diagnosis and treatment of atopic dermatitis in adult and paediatric patients

Atopic dermatitis (AD) is a clinically defined, highly pruritic, chronic inflammatory skin disease of children and adults. The diagnosis is made using evaluated clinical criteria. Disease activity is best measured with a composite score assessing both objective signs and subjective symptoms, such as SCORAD. The management of AD must consider the clinical and pathogenic variabilities of the disease

Human G protein-coupled Receptor 30 (GPR30) is N -glycosylated and N-terminal Domain Asparagine 44 is Required for Receptor Structure and Activity

GPR30, or G protein-coupled estrogen receptor (GPER), is a G protein-coupled receptor (GPCR) that is currently attracting considerable attention in breast cancer and cardiometabolic regulation. The receptor was reported to be a novel membrane estrogen receptor mediating rapid non-genomic responses. However, questions remain about both the cognate ligand and the subcellular localization of receptor

Interaction of Serum-Derived and Internalized C3 With DNA in Human B Cells-A Potential Involvement in Regulation of Gene Transcription

Beside its classical role as a serum effector system of innate immunity, evidence is accumulating that complement has an intracellular repertoire of components that provides not only immune defense, but also functions to maintain cellular homeostasis. While complement proteins, mainly the central component C3, have been detected in B cells, their exact function and source remain largely unexplored

Gephyrin Cleavage in In Vitro Brain Ischemia Decreases GABAA Receptor Clustering and Contributes to Neuronal Death

GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system, and changes in GABAergic neurotransmission modulate the activity of neuronal networks. Gephyrin is a scaffold protein responsible for the traffic and synaptic anchoring of GABAA receptors (GABAAR); therefore, changes in gephyrin expression and oligomerization may affect the activity of GABAergic syna

Efficacy and safety of the Lotus Valve System for treatment of patients with severe aortic valve stenosis and intermediate surgical risk : Results from the Nordic Lotus-TAVR registry

Background Transcatheter aortic valve replacement (TAVR) has become an established therapeutic option for patients with symptomatic, severe aortic valve stenosis (AS) who are ineligible or at high risk for conventional valvular surgery. In Northwestern Europe, the TAVR technology is also increasingly used to treat patients with an intermediate risk profile. Methods and results The study was design

Manganese concentrations in drinking water from villages near banana plantations with aerial mancozeb spraying in Costa Rica : Results from the Infants' Environmental Health Study (ISA)

Elevated manganese (Mn) in drinking water has been reported worldwide. While, naturally occurring Mn in groundwater is generally the major source, anthropogenic contamination by Mn-containing fungicides such as mancozeb may also occur. The main objective of this study was to examine factors associated with Mn and ethylenethiourea (ETU), a degradation product of mancozeb, in drinking water samples

Fuel fragmentation and fire size distributions in managed and unmanaged boreal forests in the province of Saskatchewan, Canada

Forest fires are an important disturbance factor of boreal forests, annually burning about 0.5% of the forested area in Canada. Wildfire regimes are influenced by climate and a number of studies project an increase in wildfire activity with climate change. Another factor influencing wildfires is human intervention (fire suppression), and one factor that has rarely been assessed is fuel fragmentati

Design and analysis of a reflector antenna system based on doubly curved Circular Polarization Selective Surfaces

This paper discusses the design and analysis of a reflector antenna system combining two doubly-curved Circular Polarization Selective Surfaces to provide a functionality equivalent to that of a dual gridded reflector but in circular polarization. The key feature of this design is to use a non-resonant CPSS design to avoid the bandwidth limitation of most CPSS designs previously discussed in the l

Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency - A neurometabolic disorder associated with reduced L-serine biosynthesis

3-phosphoglycerate dehydrogenase (PHGDH) deficiency is a disorder of L-serine biosynthesis that is characterized by congenital microcephaly, psychomotor retardation, and seizures. To investigate the molecular basis for this disorder, the PHGDH mRNA sequence was characterized, and six patients from four families were analyzed for sequence variations. Five patients from three different families were

Computing and visualising intra-voxel orientation-specific relaxation–diffusion features in the human brain

Diffusion MRI techniques are used widely to study the characteristics of the human brain connectome in vivo. However, to resolve and characterise white matter (WM) fibres in heterogeneous MRI voxels remains a challenging problem typically approached with signal models that rely on prior information and constraints. We have recently introduced a 5D relaxation–diffusion correlation framework wherein

Thromboembolic and bleeding risk in obese patients with atrial fibrillation according to different anticoagulation strategies

Background: Data on the relationship between body mass index (BMI), thromboembolic events (TEE) and bleeding in patients with atrial fibrillation (AF) are controversial, and further evidence on the risk of such events in obese patients with AF receiving different anticoagulant therapies (OAC) is needed. Methods and results: We divided a total of 9330 participants from the prospective PREFER in AF

Poloxamer/sodium cholate co-formulation for micellar encapsulation of doxorubicin with high efficiency for intracellular delivery : An in-vitro bioavailability study

Hypothesis: Doxorubicin hydrochloride (DX) is widely used as a chemotherapeutic agent, though its severe side-effects limit its clinical use. A way to overcome these limitations is to increase DX latency through encapsulation in suitable carriers. However, DX has a high solubility in water, hindering encapsulation. The formulation of DX with sodium cholate (NaC) will reduce aqueous solubility thro

Target position uncertainty during visually guided deep-inspiration breath-hold radiotherapy in locally advanced lung cancer

Purpose The purpose of this study was to estimate the uncertainty in voluntary deep-inspiration breath-hold (DIBH) radiotherapy for locally advanced non-small cell lung cancer (NSCLC) patients. Methods Perpendicular fluoroscopic movies were acquired in free breathing (FB) and DIBH during a course of visually guided DIBH radiotherapy of nine patients with NSCLC. Patients had liquid markers injected

Mapping past landscapes using landsat data : Upper Paraná River Basin in 1985

During the last decades, the science of remote sensing of the Earth's surface has produced an enormous amount of data. In parallel, with the increase in computational capacity, several classification methods have been applied to the satellite retrievals. This timely combination allows recovering more accurate knowledge about the land cover maps of past times. Therefore, the main goal of this work

Inborn Errors of Metabolism That Cause Sudden Infant Death : A Systematic Review with Implications for Population Neonatal Screening Programmes

Background: Many inborn errors of metabolism (IEMs) may present as sudden infant death (SID). Nowadays, increasing numbers of patients with IEMs are identified pre-symptomatically by population neonatal bloodspot screening (NBS) programmes. However, some patients escape early detection because their symptoms and signs start before NBS test results become available, they even die even before the sa

Dynamic in-situ imaging of methane hydrate formation and self-preservation in porous media

We present the results of dynamic in-situ 3D X-ray imaging of methane hydrates microstructure during methane hydrate formation and dissociation in sand samples. Short scanning times and high resolution provided by synchrotron X-rays allowed for better understanding of water movement and different types of gas-hydrate formation. Complementing previous observations, we conclude that the process of g