Transcriptional regulation of the urokinase receptor (u-PAR) - A central molecule of invasion and metastasis

The phenomenon of tumor-associated proteolysis has been acknowledged as a decisive step in the progression of cancer. This short review focuses on the urokinase receptor (u-PAR), a central molecule involved in tumor-associated invasion and metastasis, and summarizes the transcriptional regulation of u-PAR. The urokinase receptor (u-PAR) is a heavily glycosylated cell surface protein and binds the serine protease urokinase specifically and with high affinity. It consists of three similar cysteine-rich repeats and is anchored to the cell membrane via a GPI-anchor. The u-PAR gene comprises 7 exons and is located on chromosome 19q13. Transcriptional activation of the u-PAR promoter region can be induced by binding of transcription factors (Sp1, AP-1, AP-2, NF-kappaB). One current study gives an example for transcriptional downregulation of u-PAR through a PEA3/ets transcriptional silencing element. Knowledge of the molecular regulation of this molecule in tumor cells could be very important for diagnosis and therapy in the near future

Self-perceived weather sensitivity and joint pain in older people with osteoarthritis in six European countries: results from the European Project on Osteoarthritis (EPOSA)

Background: people with osteoarthritis (OA) frequently report that their joint pain is influenced by weather conditions. This study aimed to examine whether there are differences in perceived joint pain between older people with OA who reported to be weather-sensitive versus those who did not in six European countries with different climates and to identify characteristics of older persons with OA that are most predictive of perceived weather sensitivity.Methods: baseline data from the European Project on OSteoArthritis (EPOSA) were used. ACR classification criteria were used to determine OA. Participants with OA were asked about their perception of weather as influencing their pain. Using a two-week follow-up pain calendar, average self-reported joint pain was assessed (range: 0 (no pain)-10 (greatest pain intensity)). Linear regression analyses, logistic regression analyses and an independent t-test were used. Analyses were adjusted for several confounders.Results: the majority of participants with OA (67.2%) perceived the weather as affecting their pain. Weather-sensitive participants reported more pain than non-weather-sensitive participants (M?=?4.1, SD?=?2.4 versus M?=?3.1, SD?=?2.4; p?<?0.001). After adjusting for several confounding factors, the association between self-perceived weather sensitivity and joint pain remained present (B?=?0.37, p?=?0.03). Logistic regression analyses revealed that women and more anxious people were more likely to report weather sensitivity. Older people with OA from Southern Europe were more likely to indicate themselves as weather-sensitive persons than those from Northern Europe.Conclusions: weather (in)stability may have a greater impact on joint structures and pain perception in people from Southern Europe. The results emphasize the importance of considering weather sensitivity in daily life of older people with OA and may help to identify weather-sensitive older people with O

Dissipation and noise in adiabatic quantum pumps

We investigate the distribution function, the heat flow and the noise properties of an adiabatic quantum pump for an arbitrary relation of pump frequency $\omega$ and temperature. To achieve this we start with the scattering matrix approach for ac-transport. This approach leads to expressions for the quantities of interest in terms of the side bands of particles exiting the pump. The side bands correspond to particles which have gained or lost a modulation quantum $\hbar \omega$. We find that our results for the pump current, the heat flow and the noise can all be expressed in terms of a parametric emissivity matrix. In particular we find that the current cross-correlations of a multiterminal pump are directly related a to a non-diagonal element of the parametric emissivity matrix. The approach allows a description of the quantum statistical correlation properties (noise) of an adiabatic quantum pump

Abstract composition laws and their modulation spaces

On classes of functions defined on R^2n we introduce abstract composition laws modelled after the pseudodifferential product of symbols. We attach to these composition laws modulation mappings and spaces with useful algebraic and topological properties.Comment: 19 page

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10 -6) and rs8057927 in CDH13 (P=1.39 × 10 -5). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10 -7). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10 -7). This signal was replicated in the follow-up analysis (P=2.3 × 10 -2). Significant interaction with maternal CMV infection was found for rs7902091 (P SNP × CMV =7.

Sedentarismo, exercício físico e doenças crônicas

A inatividade física é fortemente relacionada à incidência e severidade de um vasto número de doenças crônicas. Assim sendo, o exercício físico torna-se uma das ferramentas terapêuticas mais importantes na promoção de saúde e o profissional de Educação Física, o responsável por sua ampla disseminação. Nesse artigo, discorremos sobre as seguintes questões: Qual o impacto - biológico e socioeconômico - da inatividade física na saúde dos indivíduos?; 2) Qual o impacto da inserção da atividade física vida dos indivíduos?; 3) Qual o papel da profissional de Educação Física na promoção de saúde e quais os desafios que a Educação Física, enquanto ciência ("lato sensu") e profissão, deve enfrentar nas próximas décadas? Tendo como ponto de partida o papel da inatividade física sobre a etiologia das doenças crônicas, pretendemos revelar o imenso potencial do exercício físico como agente terapêutico.Physical inactivity is strongly related to the incidence and severity of a number of chronic diseases. Hence, physical exercise emerges as one of the most important therapeutic tool to health promotion, with the Physical Education professional being the responsible for disseminating it widely. In this manuscript, we will discuss the following questions: 1) What is the social and biological impact of physical inactivity on overall health? 2) What is the impact of physical activity on people's lives? 3) What is the role of the Physical Education professional in the promotion of health and what are the challenges that Physical Education Discipline, as a science ("lato sensu") and profession, will face in the next decades? Having in mind the role of physical inactivity upon the etiology of chronic diseases, we intend to reveal the large potential of physical exercise as a therapeutic agent

Factors associated with functional decline in hand and hip/knee osteoarthritis after one year: data from a population‐based study

Public Health and primary careGeriatrics in primary car

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies