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Anomalous Salt Dependence Reveals an Interplay of Attractive and Repulsive Electrostatic Interactions in α-synuclein Fibril Formation

α-Synuclein (α-syn) is an intrinsically disordered protein with a highly asymmetric charge distribution, whose aggregation is linked to Parkinson’s disease. The effect of ionic strength was investigated at mildly acidic pH (5.5) in the presence of catalytic surfaces in the form of α-syn seeds or anionic lipid vesicles using thioflavin T fluorescence measurements. Similar trends were observed with

CRYAB-650 C>G (rs2234702) affects susceptibility to Type 1 diabetes and IAA-positivity in Swedish population

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabe

Exploring biomarkers associated with deteriorating vascular health using a targeted proteomics chip : The SABPA study

ABSTRACT: In this observational study, by the use of a multiplex proteomic platform, we aimed to explore associations between 92 targeted proteins involved in cardiovascular disease and/or inflammation, and phenotypes of deteriorating vascular health, with regards to ethnicity.Proteomic profiling (92 proteins) was carried out in 362 participants from the Sympathetic activity and Ambulatory Blood P

The highly expressed calcium-insensitive synaptotagmin-11 and synaptotagmin-13 modulate insulin secretion

AIM: SYT11 and SYT13, two calcium-insensitive synaptotagmins, are downregulated in islets from type-2 diabetic donors, but their function in insulin secretion is unknown. To address this, we investigated the physiological role of these two synaptotagmins in insulin secreting cells.METHODS: Correlations between gene expression levels were performed using previously described RNA-seq data on islets

Quantitative evaluation of the tibiofemoral joint cartilage by T2 mapping in patients with acute anterior cruciate ligament injury vs contralateral knees : results from the subacute phase using data from the NACOX study cohort

Objective: Immediate cartilage structural alterations in the acute phase after an anterior cruciate ligament (ACL) rupture may be a precursor to posttraumatic osteoarthritis (PTOA) development. Our aim was to describe changes in cartilage matrix in the subacute phase of the acutely ACL-injured knee compared to the contralateral uninjured knee. Design: Participants (n = 118) aged 15–40 years with a

Quantitative analysis of redox proteome reveals oxidation-sensitive protein thiols acting in fundamental processes of developmental hematopoiesis

Fetal and adult hematopoietic stem and progenitor cells (HSPCs) are characterized by distinct redox homeostasis that may influence their differential cellular behavior in normal and malignant hematopoiesis. In this work, we have applied a quantitative mass spectrometry-based redox proteomic approach to comprehensively describe reversible cysteine modifications in primary mouse fetal and adult HSPC

Tumor Suppressor Par-4 Regulates Complement Factor C3 and Obesity

Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased ab

The association between plasma metabolites and future risk of all-cause mortality

Background: Metabolite profiles provide snapshots of the overall effect of numerous exposures accumulated over life courses, which may lead to health outcomes in the future. Objective: We hypothesized that the risk of all-cause mortality is linked to alterations in metabolism earlier in life, which are reflected in plasma metabolite profiles. We aimed to identify plasma metabolites associated with

Genome Editing Using Cas9-gRNA Ribonucleoprotein in Human Pluripotent Stem Cells for Disease Modeling

The discovery that the CRISPR/Cas9 system could be used for genome editing purposes represented a major breakthrough in the field. This advancement has notably facilitated the introduction or correction of disease-specific mutations in healthy or disease stem cell lines respectively; therefore, easing disease modeling studies in combination with differentiation protocols. For many years, variabili

α-Synuclein Interaction with Lipid Bilayer Discs

α-Synuclein (aSyn) is a 140 residue long protein present in presynaptic termini of nerve cells. The protein is associated with Parkinson's disease, in which case it has been found to self-Assemble into long amyloid fibrils forming intracellular inclusions that are also rich in lipids. Furthermore, its synaptic function is proposed to involve interaction with lipid membranes, and hence, it is of in

Lessons from the pandemic : Responding to emerging zoonotic viral diseases-a Keystone Symposia report

The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be

Association of thyroid function with blood pressure and cardiovascular disease : A mendelian randomization

Thyroid function has a widespread effect on the cardiometabolic system. However, the causal association between either subclinical hyper-or hypothyroidism and the thyroid hormones with blood pressure (BP) and cardiovascular diseases (CVD) is not clear. We aim to investigate this in a two-sample Mendelian randomization (MR) study. Single nucleotide polymorphisms (SNPs) associated with thyroid-stimu

Visible chemiluminescence of ammonia premixed flames and its application for flame diagnostics

We report a spatially resolved spectroscopic study of the visible chemiluminescence emission from different premixed ammonia-air-oxygen flames stabilized on a laminar flat flame burner, with equivalence ratio ranging from 0.7 to 1.35 and an O2/N2 ratio of 0.4. In the reaction zone of the observed flames, the visible emission was recognized to be the chemiluminescence of excited NH2* radicals, whil

Review of life science applications using submicron O-PTIR and simultaneous Raman microscopy: a new paradigm in vibrational spectroscopy

The recent advent of Optical Photothermal IR (O-PTIR), has enabled for the first time, submicron infrared microscopy in far-field reflection mode with the combination of Raman for simultaneous, correlative IR+Raman microscopy. These unique and exciting synergistic capabilities are now spawning interest in life science application. A broad range of life science applications, otherwise impossible wi

Reduced acoustic resonator dimensions improve focusing efficiency of bacteria and submicron particles

In this study, we demonstrate an acoustofluidic device that enables single-file focusing of submicron particles and bacteria using a two-dimensional (2D) acoustic standing wave. The device consists of a 100 μm × 100 μm square channel that supports 2D particle focusing in the channel center at an actuation frequency of 7.39 MHz. This higher actuation frequency compared with conventional bulk acoust

New Insights in the Control of Fat Homeostasis : The Role of Neurotensin

Neurotensin (NT) is a small peptide with pleiotropic functions, exerting its primary actions by controlling food intake and energy balance. The first evidence of an involvement of NT in metabolism came from studies on the central nervous system and brain circuits, where NT acts as a neurotransmitter, producing different effects in relation to the specific region involved. Moreover, newer interesti

Evaluation of revised classification criteria for giant cell arteritis and its clinical phenotypes

Background: GCA is a systemic vasculitis of the elderly, viewed by many as a disease with multiple and overlapping clinical phenotypes. Retrospective studies have shown differences in clinical presentation between these phenotypes. To reflect the heterogeneity of GCA and novel diagnostic methods, new classification criteria have been proposed. Methods: This is a retrospective study of newly diagno

Accelerometer derived physical activity patterns in 27.890 middle-aged adults : The SCAPIS cohort study

The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at