Myxoinflammatory fibroblastic sarcoma (MIFS) with t(1;10)(p22;q24)

Review on Myxoinflammatory fibroblastic sarcoma (MIFS) with t(1;10)(p22;q24), with data on clinics, and the genes involved

Cross-national agreement on disability weights: the European Disability Weights Project

BACKGROUND: Disability weights represent the relative severity of disease stages to be incorporated in summary measures of population health. The level of agreement on disability weights in Western European countries was investigated with different valuation methods. METHODS: Disability weights for fifteen disease stages were elicited empirically in panels of health care professionals or non-health care professionals with an academic background following a strictly standardised procedure. Three valuation methods were used: a visual analogue scale (VAS); the time trade-off technique (TTO); and the person trade-off technique (PTO). Agreement among England, France, the Netherlands, Spain, and Sweden on the three disability weight sets was analysed by means of an intraclass correlation coefficient (ICC) in the framework of generalisability theory. Agreement among the two types of panels was similarly assessed. RESULTS: A total of 232 participants were included. Similar rankings of disease stages across countries were found with all valuation methods. The ICC of country agreement on disability weights ranged from 0.56 [95% CI, 0.52–0.62] with PTO to 0.72 [0.70–0.74] with VAS and 0.72 [0.69–0.75] with TTO. The ICC of agreement between health care professionals and non-health care professionals ranged from 0.64 [0.58–0.68] with PTO to 0.73 [0.71–0.75] with VAS and 0.74 [0.72–0.77] with TTO. CONCLUSIONS: Overall, the study supports a reasonably high level of agreement on disability weights in Western European countries with VAS and TTO methods, which focus on individual preferences, but a lower level of agreement with the PTO method, which focuses more on societal values in resource allocation

Clonal Evolution through Loss of Chromosomes and Subsequent Polyploidization in Chondrosarcoma

Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP) array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events

Effects of Ambulant Myofeedback Training and Ergonomic Counselling in Female Computer Workers with Work-Related Neck-Shoulder Complaints: A Randomized Controlled Trial

Objective: To investigate the effects of ambulant myofeedback training including ergonomic counselling (Mfb) and ergonomic counselling alone (EC), on work-related neck-shoulder pain and disability. Methods: Seventy-nine female computer workers reporting neck-shoulder complaints were randomly assigned to Mfb or EC and received four weeks of intervention. Pain intensity in neck, shoulders, and upper back, and pain disability, were measured at baseline, immediately after intervention, and at three and six months follow-up. Results: Pain intensity and disability had significantly decreased immediately after four weeks Mfb or EC, and the effects remained at follow up. No differences were observed between the Mfb and EC group for outcome and subjects in both intervention groups showed comparable chances for improvement in pain intensity and disability. Conclusions: Pain intensity and disability significantly reduced after both interventions and this effect remained at follow-up. No differences were observed between the two intervention groups

Illuminating the life of GPCRs

The investigation of biological systems highly depends on the possibilities that allow scientists to visualize and quantify biomolecules and their related activities in real-time and non-invasively. G-protein coupled receptors represent a family of very dynamic and highly regulated transmembrane proteins that are involved in various important physiological processes. Since their localization is not confined to the cell surface they have been a very attractive "moving target" and the understanding of their intracellular pathways as well as the identified protein-protein-interactions has had implications for therapeutic interventions. Recent and ongoing advances in both the establishment of a variety of labeling methods and the improvement of measuring and analyzing instrumentation, have made fluorescence techniques to an indispensable tool for GPCR imaging. The illumination of their complex life cycle, which includes receptor biosynthesis, membrane targeting, ligand binding, signaling, internalization, recycling and degradation, will provide new insights into the relationship between spatial receptor distribution and function. This review covers the existing technologies to track GPCRs in living cells. Fluorescent ligands, antibodies, auto-fluorescent proteins as well as the evolving technologies for chemical labeling with peptide- and protein-tags are described and their major applications concerning the GPCR life cycle are presented

Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility

BACKGROUND: Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the results of these and other studies. RESULTS: TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. CONCLUSIONS: Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13072-015-0009-5) contains supplementary material, which is available to authorized users

Advancing schizophrenia drug discovery : optimizing rodent models to bridge the translational gap

Although our knowledge of the pathophysiology of schizophrenia has increased, treatments for this devastating illness remain inadequate. Here, we critically assess rodent models and behavioural end points used in schizophrenia drug discovery and discuss why these have not led to improved treatments. We provide a perspective on how new models, based on recent advances in the understanding of the genetics and neural circuitry underlying schizophrenia, can bridge the translational gap and lead to the development of more effective drugs. We conclude that previous serendipitous approaches should be replaced with rational strategies for drug discovery in integrated preclinical and clinical programmes. Validation of drug targets in disease-based models that are integrated with translationally relevant end point assessments will reduce the current attrition rate in schizophrenia drug discovery and ultimately lead to therapies that tackle the disease process