Amyloid beta 1-40 and 1-42 fibril ratios and maturation level cause conformational differences with minimal impact on autophagy and cytotoxicity.

The amyloid β (Aβ) peptide has a central role in Alzheimer's disease (AD) pathology. The peptide length can vary between 37 and 49 amino acids, with Aβ1-42 being considered the most disease-related length. However, Aβ1-40 is also found in Aβ plaques and has shown to form intertwined fibrils with Aβ1-42.

Lack of cellular prion protein causes Amyloid β accumulation, increased extracellular vesicle abundance, and changes to exosome biogenesis proteins.

Alzheimer's disease (AD) progression is closely linked to the propagation of pathological Amyloid β (Aβ), a process increasingly understood to involve extracellular vesicles (EVs), namely exosomes. The specifics of Aβ packaging into exosomes remain elusive, although evidence suggests an ESCRT (Endosomal Sorting Complex Required for Transport)-independent origin to be responsible in spreading of AD pathogenesis. Intriguingly, PrP, known to influence exosome abundance and bind oligomeric Aβ (oAβ), can be released in exosomes via both ESCRT-dependent and ESCRT-independent pathways, raising questions about its role in oAβ trafficking.

Cellulose ether treatment inhibits amyloid beta aggregation, neuroinflammation and cognitive deficits in transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is an incurable, progressive and devastating neurodegenerative disease. Pathogenesis of AD is associated with the aggregation and accumulation of amyloid beta (Aβ), a major neurotoxic mediator that triggers neuroinflammation and memory impairment. Recently, we found that cellulose ether compounds (CEs) have beneficial effects against prion diseases by inhibiting protein misfolding and replication of prions, which share their replication mechanism with Aβ.

Non-Coding RNAs in Human Breast Milk: A Systematic Review.

Unlabelled: Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child's first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk.

Fatigue scores correlate with other self-assessment data, but not with clinical and biomarker parameters, in CIS and RRMS.

Background: Fatigue is common in multiple sclerosis and is associated with reduced quality of life. This study aimed to assess the correlation between fatigue scores and data from other self-assessment questionnaires, neuropsychological tests and neuroimaging, as well as data on neuroimmunological markers in cerebrospinal fluid (CSF) and serum/plasma, in clinically isolated syndrome (CIS) and relapsing remitting MS (RRMS).

Methods: Modified fatigue impact scale (MFIS) scores were determined in 38 patients with newly diagnosed CIS or RRMS at baseline and after one year in a prospective longitudinal cohort study.

Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance.

Background: Differential gene expression in adipose tissue during diet-induced weight loss followed by a weight stability period is poorly characterized. Markers of these processes may provide a deeper understanding of underlying mechanisms.

Objective: We aimed to identify differentially expressed genes in human adipose tissue during weight loss and weight maintenance after weight loss.

Assessment of the neuropeptide S system in anxiety disorders.

Background: The G protein-coupled receptor neuropeptide S receptor 1 (NPSR1) and its ligand neuropeptide S (NPS) form a signaling system mainly implicated in susceptibility to asthma and inflammatory disorders in humans and regulation of anxiety and arousal in rodents. We addressed here the role of NPS and NPSR1 as susceptibility genes for human anxiety disorders.

Methods: We performed comprehensive association analysis of genetic variants in NPS and NPSR1 in three independent study samples.

Genetic variance in the adiponutrin gene family and childhood obesity.

Aim: The adiponutrin gene family consists of five genes (PNPLA1-5) coding for proteins with both lipolytic and lipogenic properties. PNPLA3 has previously been associated with adult obesity. Here we investigated the possible association between genetic variants in these genes and childhood and adolescent obesity.

The visfatin (PBEF1) G-948T gene polymorphism is associated with increased high-density lipoprotein cholesterol in obese subjects.

The newly discovered adipokine visfatin has been hypothesized to be related to obesity and insulin resistance. In this study, we investigate if the 2 single nucleotide polymorphisms rs4730153 and G-948T are associated with obesity and/or related traits and whether they influence the messenger RNA (mRNA) levels of PBEF1 (originally the abbreviation for pre-B-cell colony-enhancing factor 1) in visceral and subcutaneous adipose tissue (VAT and SAT). We found that obese carriers of the PBEF1 G-948T variant allele had significantly higher levels of high-density lipoprotein cholesterol (GG, 1.

Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity.

Objective: The insulin responsive adiponutrin or patatin-like phospholipase 3 (PNPLA3, previously ADPN) gene shows association with obesity and in vitro adipocyte lipolysis. This study aimed to replicate the association between PNPLA3 variants and obesity, and to investigate their effect on insulin resistance and beta-cell function.

Methods: rs738409 (Met148Ile) and rs2072907 (C to G) were genotyped using TaqMan allelic discrimination assay in a Swedish population-based sample (n=1811).

Interaction between PPARG Pro12Ala and ADIPOQ G276T concerning cholesterol levels in childhood obesity.

Aim: The aim of this study was to investigate the role of two candidate gene polymorphisms for insulin resistance and lipid levels in obese children and adolescents.

Methods: Two markers of insulin resistance and lipid levels, Pro12Ala in peroxisome proliferator-activated receptor-gamma2 (PPARG) and G276T in adiponectin (ADIPOQ), were genotyped in 285 obese children and adolescents. As the apolipoprotein E (APOE) polymorphisms C112R and R158C are known to have a profound impact on lipid levels in both children and adults, results were adjusted for APOE genotype.

Expression of the transcription factor 7-like 2 gene (TCF7L2) in human adipocytes is down regulated by insulin.

Variants in the TCF7L2 gene (transcription factor 7-like 2) have shown strong association with type 2 diabetes with two defined risk haplotypes, HapA and HapB(T2D). TCF7L2 may play a role in both glucose homeostasis and adipogenesis. Our aim was to characterize the TCF7L2 mRNA expression and regulation in human adipose tissue.

The P2Y 13 Met-158-Thr polymorphism, which is in linkage disequilibrium with the P2Y 12 locus, is not associated with acute myocardial infarction.

Background And Aims: The aims of this study were to investigate (1) if P2Y(12) polymorphisms defining the P2Y(12) H2 allele are associated with any other SNPs that may explain the previously reported association with increased ADP induced platelet activation and association with peripheral arterial disease and coronary artery disease and (2) if such variants are associated with acute myocardial infarction (AMI) or classical risk factors for AMI.

Methods And Results: The P2Y(13) Met-158-Thr polymorphism was found to be in linkage disequilibrium (LD) with the P2Y(12) H2 haplotype (all examined SNPs: D' = 1.0, r(2) = 0.

TXNIP regulates peripheral glucose metabolism in humans.

Background: Type 2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure.

Methods And Findings: We combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose.

Variation in the adiponutrin gene influences its expression and associates with obesity.

Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes.