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The probabilistic model of Alzheimer disease : the amyloid hypothesis revised

The current conceptualization of Alzheimer disease (AD) is driven by the amyloid hypothesis, in which a deterministic chain of events leads from amyloid deposition and then tau deposition to neurodegeneration and progressive cognitive impairment. This model fits autosomal dominant AD but is less applicable to sporadic AD. Owing to emerging information regarding the complex biology of AD and the ch

Diverse ultrastructural landscape of atherosclerotic endothelium

Background and aims: The endothelium plays a major role in atherosclerosis, yet the endothelial plaque surface is a largely uncharted territory. Here we hypothesize that atherosclerosis-driven remodeling of the endothelium is a dynamic process, involving both damaging and regenerative mechanisms. Methods: Using scanning electron microscopy (SEM) and immuno-SEM, we studied endothelial junction ultr

Protein tyrosine phosphatase receptor type E (PTPRE) regulates the activation of wild-type KIT and KIT mutants differently

Activation of receptor tyrosine kinases needs tight control by tyrosine phosphatases to keep their normal function. In this study, we investigated the regulation of activation of the type III receptor tyrosine kinase KIT by protein tyrosine phosphatase receptor type E (PTPRE). We found that PTPRE can associate with wild-type KIT and inhibit KIT activation in a dose-dependent manner, although the a

Microparticle acoustophoresis in aluminum-based acoustofluidic devices with PDMS covers

We present a numerical model for the recently introduced simple and inexpensive micromachined aluminum devices with a polydimethylsiloxane (PDMS) cover for microparticle acoustophoresis. We validate the model experimentally for a basic design, where a microchannel is milled into the surface of an aluminum substrate, sealed with a PDMS cover, and driven at MHz frequencies by a piezoelectric lead-zi

Combined lentiviral- and RNA-mediated CRISPR/Cas9 delivery for efficient and traceable gene editing in human hematopoietic stem and progenitor cells

The CRISPR/Cas9 system is a versatile tool for functional genomics and forward genetic screens in mammalian cells. However, it has been challenging to deliver the CRISPR components to sensitive cell types, such as primary human hematopoietic stem and progenitor cells (HSPCs), partly due to lentiviral transduction of Cas9 being extremely inefficient in these cells. Here, to overcome these hurdles,

Mismatch between circulating cytokines and spontaneous cytokine production by leukocytes in hyperinflammatory COVID-19

The disease COVID-19 has developed into a worldwide pandemic. Hyperinflammation and high levels of several cytokines, for example, IL-6, are observed in severe COVID-19 cases. However, little is known about the cellular origin of these cytokines. Here, we investigated whether circulating leukocytes from patients with COVID-19 had spontaneous cytokine production. Patients with hyperinflammatory COV

Evaluation of the effect of base station antenna polarization on the performance of CoMP transmission techniques based on synchronous multi-link measurements

In this paper, the effect of polarization on the downlink achievable sum-rate of multi-user Cooperative Multi-Point (CoMP) systems is studied using synchronous multi-link channel measurements with two different antenna arrangements. In the first setup, four dual-polarized antenna patches with inter-patch distance varied from half wavelength to 8 m are considered at the base station (BS). In the se

Molecular and Interfacial Calculations of Iron(II) Light Harvesters

Iron-carbene complexes show considerable promise as earth-abundant light-harvesters, and adsorption onto nanostructured TiO2 is a crucial step for developing solar energy applications. Intrinsic electron injection capabilities of such promising FeII N-heterocyclic complexes (Fe-NHC) to TiO2 are calculated here, and found to correlate well with recent experimental findings of highly efficient inter

Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits : the GLACIER Study

Background:Recent cross-sectional genome-wide scans have reported associations of 97 independent loci with body mass index (BMI). In 3541 middle-aged adult participants from the GLACIER Study, we tested whether these loci are associated with 10-year changes in BMI and other cardiometabolic traits (fasting and 2-h glucose, triglycerides, total cholesterol, and systolic and diastolic blood pressures

CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion

Aims/hypothesis: Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart−/− mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affe

Comparative Proteomic Analysis of Extracellular Vesicles Isolated by Acoustic Trapping or Differential Centrifugation

Extracellular vesicles (ECVs), including microparticles and exosomes, are submicrometer membrane vesicles released by diverse cell types upon activation or stress. Circulating ECVs are potential reservoirs of disease biomarkers, and the complexity of these vesicles is significantly lower compared to their source, blood plasma, which makes ECV-based biomarker studies more promising. Proteomic profi

Tapasin facilitation of MHC-I separates closely related allomorphs, is strongly influenced by peptide length and depends on stability

Only a small fraction of the peptides inside a cell are eventually presented by HLA-I on the cell surface. The presented peptides have HLA-I allomorph-specific motifs and length restrictions. Tapasin influences HLA-I antigen presentation both qualitatively and quantitatively to different degrees depending on both peptide sequence and HLA-I allomorph. The tapasin-dependence in cellular context has

In embryonic stem cells, ZFP57/KAP1 recognize a methylated hexanucleotide to affect chromatin and DNA methylation of imprinting control regions

The maintenance of H3K9 and DNA methylation at imprinting control regions (ICRs) during early embryogenesis is key to the regulation of imprinted genes. Here, we reveal that ZFP57, its cofactor KAP1, and associated effectors bind selectively to the H3K9me3-bearing, DNA-methylated allele of ICRs in ES cells. KAP1 deletion induces a loss of heterochromatin marks at ICRs, whereas deleting ZFP57 or DN

The association between adult attained height and sitting height with mortality in the European prospective investigation into cancer and nutrition (EPIC)

Adult height and sitting height may reflect genetic and environmental factors, including early life nutrition, physical and social environments. Previous studies have reported divergent associations for height and chronic disease mortality, with positive associations observed for cancer mortality but inverse associations for circulatory disease mortality. Sitting height might be more strongly asso

Surgical management of degenerative meniscus lesions : the 2016 ESSKA meniscus consensus

Purpose: A degenerative meniscus lesion is a slowly developing process typically involving a horizontal cleavage in a middle-aged or older person. When the knee is symptomatic, arthroscopic partial meniscectomy has been practised for a long time with many case series reporting improved patient outcomes. Since 2002, several randomised clinical trials demonstrated no additional benefit of arthroscop

Variation in laying date in relation to spring temperature in three species of tits (Paridae) and pied flycatchers Ficedula hypoleuca in southernmost Sweden

This study documents the advancement of laying dates in three species of tits (Paridae) in southernmost Sweden during recent decades, and the absence of a similar response in the pied flycatcher Ficedula hypoleuca. It is based on several different nestbox studies; the oldest one starting in 1969. During 1969 to 2012, mean spring temperatures in the study area increased by between 0.06 and 0.08 °C This study documents the advancement of laying dates in three species of tits (Paridae) in southernmost Sweden during recent decades, and the absence of a similar response in the pied flycatcher Ficedula hypoleuca. It is based on several different nestbox studies; the oldest one starting in 1969. During 1969 to 2012, mean spring temperatures in the study area increased by between 0.06 and 0.08°C p

A developmental etiological model for drug abuse in men

Background We attempt to develop a relatively comprehensive structural model of risk factors for drug abuse (DA) in Swedish men that illustrates developmental and mediational processes. Methods We examined 20 risk factors for DA in 48,369 men undergoing conscription examinations in 1969–70 followed until 2011 when 2.34% (n = 1134) of them had DA ascertained in medical, criminal and pharmacy regist

Heparin-binding protein, lysozyme, and inflammatory cytokines in bronchoalveolar lavage fluid as diagnostic tools for pulmonary infection in lung transplanted patients

Pulmonary infection is a common complication after lung transplantation, and early detection is crucial for outcome. However, the condition can be clinically difficult to diagnose and to distinguish from rejection. The aim of this prospective study was to evaluate heparin-binding protein (HBP), lysozyme, and the cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF) in br