Health inequalities in Germany: do regional-level variables explain differentials in cardiovascular risk?

Breckenkamp J, Mielck A, Razum O. Health inequalities in Germany: do regional-level variables explain differentials in cardiovascular risk? BMC Public Health. 2007;7(1): 132.Background: Socioeconomic status is a predictor not only of mortality, but also of cardiovascular risk and morbidity. An ongoing debate in the field of social inequalities and health focuses on two questions: 1) Is individual health status associated with individual income as well as with income inequality at the aggregate (e. g. regional) level? 2) If there is such an association, does it operate via a psychosocial pathway (e.g. stress) or via a ´´neo-materialistic´´ pathway (e.g. systematic under-investment in societal infrastructures)? For the first time in Germany, we here investigate the association between cardiovascular health status and income inequality at the area level, controlling for individual socio-economic status. Methods: Individual-level explanatory variables (age, socio-economic status) and outcome data (body mass index, blood pressure, cholesterol level) as well as the regional-level variable (proportion of relative poverty) were taken from the baseline survey of the German Cardiovascular Prevention Study, a cross-sectional, community-based, multi-center intervention study, comprising six socio-economically diverse intervention regions, each with about 1800 participants aged 25–69 years. Multilevel modeling was used to examine the effects of individual and regional level variables. Results: Regional effects are small compared to individual effects for all risk factors analyzed. Most of the total variance is explained at the individual level. Only for diastolic blood pressure in men and for cholesterol in both men and women is a statistically significant effect visible at the regional level. Conclusion: Our analysis does not support the assumption that in Germany cardiovascular risk factors were to a large extent associated with income inequality at regional level

The serologically defined colon cancer antigen-3 (SDCCAG3) is involved in the regulation of ciliogenesis

A primary cilium is present on most eukaryotic cells and represents a specialized organelle dedicated to signal transduction and mechanosensing. Defects in cilia function are the cause for several human diseases called ciliopathies. The serologically defined colon cancer antigen-3 (SDCCAG3) is a recently described novel endosomal protein mainly localized at early and recycling endosomes and interacting with several components of membrane trafficking pathways. Here we describe localization of SDCCAG3 to the basal body of primary cilia. Furthermore, we demonstrate that decreased expression levels of SDCCAG3 correlate with decreased ciliary length and a reduced percentage of ciliated cells. We show that SDCCAG3 interacts with the intraflagellar transport protein 88 (IFT88), a crucial component of ciliogenesis and intraciliary transport. Mapping experiments revealed that the N-terminus of SDCCAG3 mediates this interaction by binding to a region within IFT88 comprising several tetratricopeptide (TRP) repeats. Finally, we demonstrate that SDCCAG3 is important for ciliary localization of the membrane protein Polycystin-2, a protein playing an important role in the formation of polycystic kidney disease, but not for Rab8 another ciliary protein. Together these data suggest a novel role for SDCCAG3 in ciliogenesis and in localization of cargo to primary cilia

Drilling Predation on Serpulid Polychaetes (Ditrupa arietina) from the Pliocene of the Cope Basin, Murcia Region, Southeastern Spain

We report quantitative analyses of drilling predation on the free-living, tube-dwelling serpulid polychaete Ditrupa arietina from the Cope Cabo marine succession (Pliocene, Spain). Tubes of D. arietina are abundant in the sampled units: 9 bulk samples from 5 horizons yielded ∼5925 specimens of D. arietina. Except for fragmentation, tubes were well preserved. Complete specimens ranged from 3.1 to 13.4 mm in length and displayed allometric growth patterns, with larger specimens being relatively slimmer. Drilled Ditrupa tubes were observed in all samples. Drillholes, identified as Oichnus paraboloides, were characterized by circular to elliptical outline (drillhole eccentricity increased with its diameter), parabolic vertical profile, outer diameter larger than inner diameter, penetration of one tube wall only, narrow range of drill-hole sizes, and non-random (anterior) distribution of drillholes. A total of 233 drilled specimens were identified, with drilling frequencies varying across horizons from 2.7% to 21% (3.9% for pooled data). Many tube fragments were broken across a drillhole suggesting that the reported frequencies are conservative and that biologically-facilitated (drill-hole induced) fragmentation hampers fossil preservation of complete serpulid tubes. No failed or repaired holes were observed. Multiple complete drillholes were present (3.9%). Drilled specimens were significantly smaller than undrilled specimens and tube length and drill-hole diameter were weakly correlated. The results suggest that drillholes were produced by a size-selective, site-stereotypic predatory organism of unknown affinity. The qualitative and quantitative patterns reported here are mostly consistent with previous reports on recent and fossil Ditrupa and reveal parallels with drilling patterns documented for scaphopod mollusks, a group that is ecologically and morphologically similar to Ditrupa. Consistent with previous studies, the results suggest that free-dwelling serpulid polychaetes are preyed upon by drilling predators and may provide a viable source of data on biotic interactions in the fossil record

Mu-Opioid Receptors Transiently Activate the Akt-nNOS Pathway to Produce Sustained Potentiation of PKC-Mediated NMDAR-CaMKII Signaling

BACKGROUND: In periaqueductal grey (PAG) matter, cross-talk between the Mu-opioid receptor (MOR) and the glutamate N-methyl-D-Aspartate receptor (NMDAR)-CaMKII pathway supports the development of analgesic tolerance to morphine. In neurons, histidine triad nucleotide binding protein 1 (HINT1) connects the regulators of G protein signaling RGSZ1 and RGSZ2 to the C terminus of the MOR. In response to morphine, this HINT1-RGSZ complex binds PKCgamma, and afterwards, the interplay between PKCgamma, Src and Gz/Gi proteins leads to sustained potentiation of NMDAR-mediated glutamate responses. METHODOLOGY/PRINCIPAL FINDINGS: Following an intracerebroventricular (icv) injection of 10 nmol morphine, Akt was recruited to the synaptosomal membrane and activated by Thr308 and Ser473 phosphorylation. The Akt activation was immediately transferred to neural Nitric Oxide Synthase (nNOS) Ser1417. Afterwards, nitric oxide (NO)-released zinc ions recruited PKCgamma to the MOR to promote the Src-mediated phosphorylation of the Tyr1325 NMDAR2A subunit. This action increased NMDAR calcium flux and CaMKII was activated in a calcium-calmodulin dependent manner. CaMKII then acted on nNOS Ser847 to produce a sustained reduction in NO levels. The activation of the Akt-nNOS pathway was also reduced by the binding of these proteins to the MOR-HINT1 complex where they remained inactive. Tolerance to acute morphine developed as a result of phosphorylation of MOR cytosolic residues, uncoupling from the regulated G proteins which are transferred to RGSZ2 proteins. The diminished effect of morphine was prevented by LNNA, an inhibitor of nNOS function, and naltrindole, a delta-opioid receptor antagonist that also inhibits Akt. CONCLUSIONS/SIGNIFICANCE: Analysis of the regulatory phosphorylation of the proteins included in the study indicated that morphine produces a transient activation of the Akt/PKB-nNOS pathway. This activation occurs upstream of PKCgamma and Src mediated potentiation of NMDAR activity, ultimately leading to morphine tolerance. In summary, the Akt-nNOS pathway acts as a primer for morphine-triggered events which leads to the sustained potentiation of the NMDAR-CaMKII pathway and MOR inhibition

Operons

Operons (clusters of co-regulated genes with related functions) are common features of bacterial genomes. More recently, functional gene clustering has been reported in eukaryotes, from yeasts to filamentous fungi, plants, and animals. Gene clusters can consist of paralogous genes that have most likely arisen by gene duplication. However, there are now many examples of eukaryotic gene clusters that contain functionally related but non-homologous genes and that represent functional gene organizations with operon-like features (physical clustering and co-regulation). These include gene clusters for use of different carbon and nitrogen sources in yeasts, for production of antibiotics, toxins, and virulence determinants in filamentous fungi, for production of defense compounds in plants, and for innate and adaptive immunity in animals (the major histocompatibility locus). The aim of this article is to review features of functional gene clusters in prokaryotes and eukaryotes and the significance of clustering for effective function

Benefit finding and posttraumatic growth in long-term colorectal cancer survivors: prevalence, determinants, and associations with quality of life

BACKGROUND: As research on quality of life of colorectal cancer (CRC) survivors has mainly focused on downsides of cancer survivorship, the aim of this study is to investigate benefit finding (BF) and post-traumatic growth (PTG) in long-term CRC survivors. METHODS: Benefit finding, PTG, and quality of life were assessed 5 years after diagnosis in a population-based cohort of 483 CRC patients using the benefit finding scale, the post-traumatic growth inventory, and the EORTC QLQ-C30. Prevalence of BF and PTG, determinants of moderate-to-high BF and PTG, and the association between BF, PTG, and quality of life were investigated. RESULTS: Moderate to high levels of BF and PTG were experienced by 64% and 46% of the survivors, respectively. Survivors with the highest level of education and with higher depression scores reported less BF and PTG. The PTG increased with increasing stage and self-reported burden of diagnosis. Quality of life only correlated weakly with PTG (Pearson's r=0.1180, P=0.0112) and not with BF (r=0.0537, P=0.2456). CONCLUSION: Many long-term CRC survivors experience BF and PTG. As these constructs were not strongly correlated with quality of life, focusing solely on quality of life after cancer misses an important aspect of survivorship