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Reduced protein solubility - cause or consequence in amyloid disease?

In this perspective, we ask the question whether the apparently lower solubility of specific proteins in amyloid disease is a cause or consequence of the protein deposition seen in such diseases. We focus on Alzheimer's disease and start by reviewing the experimental evidence of disease-associated reduction in the measured concentration of amyloid β peptide, Aβ42, in cerebrospinal fluid. We propos

Combined Multicolor Immunofluorescence Staining and Spatial In Situ messenger RNA Expression Analysis Identifies Potential Fibrosis Drivers in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most prevalent childhood cancer. Bone marrow (BM) fibrosis in ALL has been associated with adverse outcomes; however, little is known about the mechanisms that cause fibrosis in ALL. Therefore, we established a novel and advanced analysis method by combining multicolor immunofluorescence (IF) staining with in situ RNA expression analysis (RNAscope) to inve

Kinetics of seeded protein aggregation : Theory and application

“Seeding” is the addition of preformed fibrils to a solution of monomeric protein to accelerate its aggregation into new fibrils. It is a versatile and widely used tool for scientists studying protein aggregation kinetics, as it enables the isolation and separate study of discrete reaction steps contributing to protein aggregation, specifically elongation and secondary nucleation. However, the see

Altered co-expression patterns of synovial fluid proteins related to the immune system and extracellular matrix organization in late stage OA, compared to non-OA controls

Objective: Synovial fluid contains proteins that may have been released from surrounding tissues, our aim was to gain new insights into the proteomic profiles of human synovial fluid in knees with and without osteoarthritis (OA). Methods: We used synovial fluid from 11 patients with end-stage medial compartment knee OA, aspirated during total knee replacement, and from 13 deceased donors who had n

High-efficiency microwave photodetection by cavity-coupled double quantum dots with single-cavity-photon sensitivity

We present a superconducting cavity-coupled double quantum dot (DQD) photodiode that achieves a maximum photon-to-electron conversion efficiency of 25% in the microwave domain. With a higher-quality-factor cavity and improved device design to prevent photon leakages through unwanted pathways, our device measures microwave signals down to the 100-aW power level and achieves sensitivity to probe mic

Fiber length and shape-dependent differences in hepatic nanomaterial localization in mice following pulmonary exposure

Background: Inhaled nanomaterials can translocate from the lungs into systemic circulation and reach the liver, which is the main secondary organ for nanomaterial uptake, potentially causing adverse effects. Understanding how inhaled nanomaterials localize within liver tissue is important for understanding their clearance mechanisms and potential toxicity. Previous in vivo studies have primarily f

Flame soot characterization using combined multi-wavelength thermo-optical analysis and Raman spectroscopy

Multi-wavelength thermo-optical analysis (MW-TOA) and Raman spectroscopy are commonly used methods to study soot sampled on filters, in terms of carbon content, nanostructure, and absorption properties. In this work, these techniques were combined to study how these characteristic properties of soot change in premixed flames, 1) at various flame heights during soot maturation and 2) as a result of

Contribution of indoor-generated particles to residential exposure

Abstract The majority of airborne particles in residences, when expressed as number concentrations, are generated by the residents themselves, through combustion/thermal related activities. These particles have a considerably smaller diameter than 2.5 μm and, due to the combination of their small size, chemical composition (e.g. soot) and intermittently very high concentrations, should be regard

Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation.

Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson's disease. However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We ind

Low Levels of Apolipoprotein B-100 Autoantibodies Are Associated With Increased Risk of Coronary Events.

OBJECTIVE: Previous smaller studies have indicated inverse associations between autoantibodies to oxidized low-density lipoprotein epitopes, and cardiovascular disease. The present study investigated associations between autoantibodies against the apolipoprotein B-100 peptides p45 and p210, respectively, and risk of incident cardiovascular disease in a large population-based cohort. APPROACH AND

Chromosome 9p21 genetic variation explains 13% of cardiovascular disease incidence but does not improve risk prediction.

OBJECTIVES: To evaluate the proportion of cardiovascular disease (CVD) incidence that is explained by genetic variation at chromosome 9p21 and to test whether such variation adds incremental information with regard to CVD prediction, beyond traditional risk factors. DESIGN, SETTING AND PARTICIPANTS: rs4977574 on chromosome 9p21 was genotyped in 24 777 subjects from the Malmö Diet and Cancer study

Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation.

Soluble urokinase plasminogen activator receptor (suPAR) in plasma is a novel inflammatory marker thought to be released from the cell surface of neutrophils, T cells, and macrophages. Other inflammatory markers, mainly acute phase proteins produced in the liver, have been associated with the incidence of heart failure (HF) and atrial fibrillation (AF). We investigated the association between suPA

Soluble urokinase plasminogen activator receptor in plasma is associated with incidence of CVD. Results from the Malmö Diet and Cancer Study.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a highly sensitive marker that reflects increased inflammation and is positively correlated with pro-inflammatory biomarkers. The aim of this study was to explore the relationship between suPAR, cardiovascular disease (CVD) risk factors and incidence of CVD. METHODS: suPAR was assessed in a random sample of participants (N=569

Low expression of SHP-2 is associated with less favorable prostate cancer outcomes.

ABSTACT: Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is an important regulator of cell signaling because of its ability to dephosphorylate receptors of growth factors as well as the cytokines and tyrosine-phosphorylated proteins associated with these receptors. In the current study, we used four different prostate cancer cell lines: PC3, DU145, LNCaP and LNCaP-IL6+. Tumor speci

Adrenomedullin is a marker of carotid plaques and intima-media thickness as well as brachial pulse pressure.

Adrenomodulin (ADM) is a peptide hormone secreted in response to cellular strain such as ischemia and is believed to have a beneficial effect on the cardiovascular system. However, the epidemiological relationships between ADM and measurements of haemodynamics, arteriosclerosis and atherosclerosis are not well established. The aim of this study was to investigate the association between the mid-re

Ceruloplasmin and atrial fibrillation: evidence of causality from a population-based Mendelian randomization study.

Inflammatory diseases and inflammatory markers secreted by the liver, including C-reactive protein (CRP) and ceruloplasmin, have been associated with incident atrial fibrillation (AF). Genetic studies have not supported a causal relationship between CRP and AF, but the relationship between ceruloplasmin and AF has not been studied. The purpose of this Mendelian randomization study was to explore w

Altered profile of basket cell afferent synapses in hyper-excitable dentate gyrus revealed by optogenetic and two-pathway stimulations.

Cholecystokinin (CCK-) positive basket cells form a distinct class of inhibitory GABAergic interneurons, proposed to act as fine-tuning devices of hippocampal gamma-frequency (30-90 Hz) oscillations, which can convert into higher frequency seizure activity. Therefore, CCK-basket cells may play an important role in regulation of hyper-excitability and seizures in the hippocampus. In normal conditio

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated thro

Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens

Human fetal midbrain tissue grafting has provided proof-of-concept for dopamine cell replacement therapy (CRT) in Parkinson's disease (PD). However, limited tissue availability has hindered the development and widespread use of this experimental therapy. Here we present a method for generating large numbers of midbrain dopaminergic (DA) neurons based on expanding and differentiating neural stem/pr