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Associations in Perceived Health and Persistent Breathlessness: A Cross-Sectional Study

Background: Persistent breathlessness is debilitating and increases in prevalence with advanced age and at end of life. This study aimed to evaluate any relationship between self-reported global impressions of change (GIC) in perceived health and breathlessness in older men.Design: Cross-sectional study of 73-year-old Swedish men in the VAScular and Chronic Obstructive Lung disease study. A postal

Modelling human rostro-caudal neural patterning with a microfluidic morphogenic gradient

The study of biological mechanisms involved in human fetal brain development requires suitable models. To date, most findings have been acquired from animal models that fail to account for human-specific developmental traits. To counteract this limitation, a novel in vitro model is proposed where human pluripotent stem cells are differentiated into a coherent fetal brain tissue in a gradient formi

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

Direct role of FLT3 in regulation of early lymphoid progenitors

Given that FLT3 expression is highly restricted on lymphoid progenitors, it is possible that the established role of FLT3 in the regulation of B and T lymphopoiesis reflects its high expression and role in regulation of lymphoid-primed multipotent progenitors (LMPPs) or common lymphoid progenitors (CLPs). We generated a Flt3 conditional knock-out (Flt3fl/fl) mouse model to address the direct role

Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6 dependent manner

Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apopt

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

Coffee, tea and melanoma risk : findings from the European Prospective Investigation into Cancer and Nutrition

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EP

Genome-wide RNAi Screen Identifies Cohesin Genes as Modifiers of Renewal and Differentiation in Human HSCs

To gain insights into the regulatory mechanisms of hematopoietic stem cells (HSCs), we employed a genome-wide RNAi screen in human cord-blood derived cells and identified candidate genes whose knockdown maintained the HSC phenotype during culture. A striking finding was the identification of members of the cohesin complex (STAG2, RAD21, STAG1, and SMC3) among the top 20 genes from the screen. Upon

Pre-diagnostic meat and fibre intakes in relation to colorectal cancer survival in the European Prospective Investigation into Cancer and Nutrition

Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival a

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

Protein Expression in Metastatic Melanoma and the Link to Disease Presentation in a Range of Tumor Phenotypes

Malignant melanoma is among the most aggressive skin cancers and it has among the highest metastatic potentials. Although surgery to remove the primary tumor is the gold standard treatment, once melanoma progresses and metastasizes to the lymph nodes and distal organs, i.e., metastatic melanoma (MM), the usual outcome is decreased survival. To improve survival rates and life span, advanced treatme

Preserved function of afferent parvalbumin-positive perisomatic inhibitory synapses of dentate granule cells in rapidly kindled mice

Parvalbumin- (PV-) containing basket cells constitute perisomatic GABAergic inhibitory interneurons innervating principal cells at perisomatic area, a strategic location that allows them to efficiently control the output and synchronize oscillatory activity at gamma frequency (30–90 Hz) oscillations. This oscillatory activity can convert into higher frequency epileptiform activity, and therefore c

Physical activity and survival following breast cancer

INTRODUCTION:Physical activity (PA) leads to improved survival in women following the diagnosis of breast cancer, but it is less clear whether PA has equally positive effects regardless of age at diagnosis. The purpose of our study was to evaluate the association between post-diagnosis PA and survival in women aged below or over 55 years at diagnosis.METHODS:From a prospective population-based coh