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Analysis of Alpha-Synuclein in Malignant Melanoma - Development of a SRM Quantification Assay.

Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease pr

Thermostable Phytase from a Bacillus sp.: Heterologous Production, Mutation, Characterization and Assay Development

Phytase is an important enzyme in the food/feed industry. It catalyzes the hydrolysis of phytate, an anti-nutrient compound present in cereals and grains, to release orthophosphate and myo-inositol-6-phosphate with lower degrees of phosphorylation. Phytic acid is a strong chelator capable of complexing with a variety of metal ions under neutral and alkaline conditions, as well as with proteins and

Genetic profiles of gastroesophageal cancer: combined analysis using expression array and tiling array-comparative genomic hybridization

We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas by means of 32k high-resolution array-based comparative genomic hybridization and 27k oligo gene expression arrays, and putative

A protein deep sequencing evaluation of metastatic melanoma tissues.

Malignant melanoma has the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has very limited possibilities for cure. Recently, several protein kinase inhibitors and immune modifiers have shown promising clinical results but drug resistance in metastasized melanoma remains a major pr

Different fractions of human serum glycoproteins bind galectin-1 or galectin-8, and their ratio may provide a refined biomarker for pathophysiological conditions in cancer and inflammatory disease.

BACKGROUND: Changes in glycosylation of serum proteins are common, and various glycoforms are being explored as biomarkers in cancer and inflammation. We recently showed that glycoforms detected by endogenous galectins not only provide potential biomarkers, but also have different functions when they encounter galectins in tissue cells. Now we have explored the use of a combination of two galectin

Type 2 diabetes, adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting

Type 2 diabetes (T2D) and adiposity associate with increased risk of several cancers, but the impact of competing risk of noncancer deaths on these associations is not known. We prospectively examined participants in the Malmö Diet and Cancer Study aged 44–73 years with no history of cancer at baseline (n = 26,953, 43% men). T2D was ascertained at baseline and during follow-up, and body mass index

Biomarkers of microvascular endothelial dysfunction predict incident dementia : a population-based prospective study

BACKGROUND: Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and s

Cytohesin 1 regulates homing and engraftment of human hematopoietic stem and progenitor cells

Adhesion is a key component of hematopoietic stem cell regulation mediating homing and retention to the niche in the bone marrow. Here, using an RNA interference screen, we identify cytohesin 1 (CYTH1) as a critical mediator of adhesive properties in primary human cord blood-derived hematopoietic stem and progenitor cells (HSPCs). Knockdown of CYTH1 disrupted adhesion of HSPCs to primary human mes

Direct reprogramming of fibroblasts into antigen-presenting dendritic cells

Ectopic expression of transcription factors has been used to reprogram differentiated somatic cells toward pluripotency or to directly reprogram them to other somatic cell lineages. This concept has been explored in the context of regenerative medicine. Here, we set out to generate dendritic cells (DCs) capable of presenting antigens from mouse and human fibroblasts. By screening combinations of 1

Elevated circulating effector memory T cells but similar levels of regulatory T cells in patients with type 2 diabetes mellitus and cardiovascular disease

Type 2 diabetes mellitus is associated with an elevated risk of cardiovascular disease, but the mechanism through which diabetes contributes to cardiovascular disease development remains incompletely understood. In this study, we compared the association of circulating regulatory T cells, naïve T cells, effector memory T cells or central memory T cells with cardiovascular disease in patients with

MafA expression preserves immune homeostasis in human and mouse islets

Type 1 (T1D) and type 2 (T2D) diabetes are triggered by a combination of environmental and/or genetic factors. Maf transcription factors regulate pancreatic beta (β)-cell function, and have also been implicated in the regulation of immunomodulatory cytokines like interferon-β (IFNβ1). In this study, we assessed MAFA and MAFB co-expression with pro-inflammatory cytokine signaling genes in RNA-seq d

Echocardiographic right ventricular strain from multiple apical views is superior for assessment of right ventricular systolic function

Background: Right ventricular (RV) systolic function is an important determinant of outcome in patients with pulmonary hypertension (PH). Conventional echocardiographic measures of RV are mainly based on longitudinal contractility. Recently, measurement of RV global longitudinal strain derived from multiple windows (RVGLS) has emerged as an option but has not been well evaluated. The aim of the pr

Evaluation of reproducibility in MRI quantitative volumetric assessment and its role in the prediction of overall survival and progression-free survival in glioblastoma

Background: Residual tumor volume (RTV) and extent of resection (EOR) have previously been shown to affect survival in glioblastoma (GB) patients. Quantitative radiological assessment (QRA) of these factors could potentially affect clinical decision-making in the postoperative period. Purpose: The first aim was to evaluate the reproducibility of different volume estimation methods of RTV and EOR b

Perfusion in Upper Eyelid Flaps : Effects of Rotation and Stretching Measured With Laser Speckle Contrast Imaging in Patients

PURPOSE: The aim of this study was to investigate how the blood perfusion in human upper eyelid skin flaps is affected by the length of the flap and the degree of stretching and rotation of the flap.METHODS: Twenty-nine upper eyelids were dissected as part of a blepharoplastic procedure in patients. The 1-cm wide proximal end of the flap remains attached, to mimic a random pattern skin flap (herea

Aerosolization and recovery of viable murine norovirus in an experimental setup

Noroviruses are the major cause for viral acute gastroenteritis in the world. Despite the existing infection prevention strategies in hospitals, the disease continues to spread and causes extensive and numerous outbreaks. Hence, there is a need to investigate the possibility of airborne transmission of norovirus. In this study, we developed an experimental setup for studies on the infectivity of a

Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer (NSCLC) risk, biological mechanisms of these variants remain largely unknown. By integrating a large-scale genotype data of 15 581 lung adenocarcinoma (AD) cases, 8350 squamous cell carcinoma (SqCC) cases, and 27 355 controls, as well as multiple transcriptome and e

Loss of Cxcr5 alters neuroblast proliferation and migration in the aged brain

Neurogenesis, the production of new neurons from neural stem cells, dramatically decreases during aging concomitantly with increased inflammation both systemically and in the brain. However, the precise role of inflammation and whether local or systemic factors drive the neurogenic decline during aging is poorly understood. Here, we identify CXCR5/5/CXCL13 signaling as a novel regulator of neuroge

S100A6 is a critical regulator of hematopoietic stem cells.

The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration, and apoptosis. HSCs self-renewal divisions in stem cells are required for rapid regeneration during tissue damage and stress, but how precisely intracellular calcium signals are regulated to maintain fate options in normal hematopoiesis is unclear. S100A6 knockout (KO) HSCs have reduced total cell

Antisense regulation of atrial natriuretic peptide expression

The cardiac hormone atrial natriuretic peptide (ANP) is a central regulator of blood volume and a therapeutic target in hypertension and heart failure. Enhanced ANP activity in such conditions through inhibition of the degradative enzyme neprilysin has shown clinical efficacy but is complicated by consequences of simultaneous accumulation of a heterogeneous array of other hormones. Targets for spe

Evaluation of TH-Cre knock-in cell lines for detection and specific targeting of stem cell-derived dopaminergic neurons

The focal and progressive degeneration of dopaminergic (DA) neurons in ventral midbrain has made Parkinson's disease (PD) a particularly interesting target of cell-based therapies. However, ethical issues and limited tissue availability have so far hindered the widespread use of human fetal tissue in cell-replacement therapy. DA neurons derived from human pluripotent stem cells (hPSCs) offer unpre