DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.     

Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives

Resistance to chemotherapy still remains a major challenge in the clinic, impairing the quality of life and survival rate of patients. The identification of unconventional chemosensitizing agents is therefore an interesting aspect of cancer research. Resveratrol has emerged in the last decades as a fascinating molecule, able to modulate several cancer-related molecular mechanisms, suggesting a possible application as an adjuvant in cancer management. This review goes deep into the existing literature concerning the possible chemosensitizing effect of resveratrol associated with the most conventional chemotherapeutic drugs. Despite the promising effects observed in different cancer types in in vitro studies, the clinical translation still presents strong limitations due to the low bioavailability of resveratrol. Recently, efforts have been moved in the field of drug delivery to identifying possible strategies/formulations useful for a more effective administration. Despite the necessity of a huge implementation in this research area, resveratrol appears as a promising molecule able to sensitize resistant tumors to drugs, suggesting its potential use in therapy-refractory cancer patients.     

Experimental methods in hepatology. Guidelines of the German Association for the Study of the Liver (GASL). Liver perfusion--technique and applications

Purified cell-envelope polyphosphatase as well as polyphoshatase activities of cytosol and isolated vacuoles, of nuclei and mitochondria of the yeast Saccharomyces cerevisiae were compared. The polyphosphatases of cell envelope and cytosol are similar, the polyphosphatases of nuclei, vacuoles and mitochondria differ in their kinetic properties, substrate specificity, requirements in divalent cations and in some effector actions both from these and from each other.     

Increased concentrations of octachlorodibenzo-p-dioxin in cases with breast cancer--results from a case-control study

Organochlorines are persistent and highly lipophilic environmental contaminants which bioaccumulate in the food chain. Some of these chemicals, 2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane (DDT) and polychlorinated biphenyls (PCBs), have been suggested to be of significance in the aetiology of breast cancer. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an anti-oestrogen in animal studies and should be thus lower the risk of breast cancer. The other isomers of polychlorinated dibenzo-p-dioxins (PCDDs) or the chemically related polychlorinated dibenzofurans (PCDFs) have not been tested regarding carcinogenesis of the breast. The purpose of this study was to investigate whether PCDDs or PCDFs influence the risk for breast cancer. Consecutive patients who underwent surgery for a breast disease between 1993 and 1995 were recruited for the study. Cases were 22 patients with infiltrative breast cancer and controls were 19 patients operated for a benign breast disease during the same time period. Approximately 10 g of breast tissue free from tumour was taken from the specimen and frozen until analysis. Fat was extracted, cleaned and analysed with a high-resolution gas chromatograph coupled to a high-resolution mass spectrometer. Median concentrations of octachlorinated dibenzo-p-dioxin (OCDD) were 598 (170-14,880) and 396 (103-1,847) pg/g lipid in the cases and in the controls, respectively. In a multivariate logistic regression analysis controlling for other risk factors for breast cancer increased odds ratio (OR) was obtained for OCDD: 401-1000 pg/g lipid yielded OR 3.8, 95% confidence interval (CI) 0.4-39, > 1000 pg/g lipid gave OR 5.2, CI 0.4-72. When the lipid OCDD variable was examined as a continuous risk factor there was a 1.09 (9%), CI 0.95-1.25, increase in the adjusted OR for breast cancer per 100 unit (pg/g lipid) increase in OCDD. No differences were found between cases and controls for the other six tested PCDDs. Mean concentration of TCDD was in the cases 3.6 (1.0-7.9) and in the controls 3.3 (1.1-6.3) pg/g lipid. For PCDFs no significant differences were found between cases and controls. The results were not changed if oestrogen or progesterone receptor status, S-phase fraction and DNA ploidy were considered. Breast tissue concentration of OCDD was increased in cancer patients, whereas the concentrations of other PCDDs and PCDFs were equal in cases and controls.     

DILIGENT: integrating digital library and Grid technologies for a new Earth observation research infrastructure

This paper introduces DILIGENT, a digital library infrastructure built by integrating digital library and Grid technologies and resources. This infrastructure allows different communities to dynamically build specialised digital libraries capable to support the entire e-Science knowledge production and consumption life-cycle by using shared computing, storage, content, and application resources. The paper presents some of the main software services that implement the DILIGENT system. Moreover, it exemplifies the provided features by presenting how the DILIGENT infrastructure is being exploited in supporting the activity of user communities working in the Earth Science Environmental sector. This work is partially funded by the European Commission in the context of the DILIGENT project, under the 2nd call of FP6 IST priority.     

ALUM SHALE BITUMEN MATURATION AND MIGRATION: IMPLICATIONS FOR GOTLAND'S OIL

Thermal maturation of Swedish Alum Shale kerogen and bitumen has been determined from core samples from Eastern and Central Sweden. In samples from Eastern Sweden (Öland and Gotland), the kerogen and bitumen are thermally immature with respect to petroleum generation. In some areas of Central Sweden (Närke, ÖstergÖtland, and Kinnekulle in VästergÖtland), the kerogen is immature, whereas the bitumen is marginally mature to mature. In other areas of Central Sweden (Halleberg-Hunneberg in VästergÖtland), the kerogen is supermature and the bitumen mature. This suggests that bitumen from a mature source-rock has migrated into the Alum Shales of Central Sweden. Migration in Central Sweden is further evidenced by the occurrence of obviously-migrated bituments in vugs and voids in the organicpoor Ordovician limestone overlying the Alum Shale in Central Sweden, and in concretions within the Alum Shale itself. Based on biomarker distributions of extracted bitumen, Alum Shale kerogen pyrolysate and obviously-migrated oils, and the fact that the Alum Shale in most of the areas studied is the only petroleum source-rock extant, it is suggested that the migrated bitumen in Central Sweden is from the Alum Shale itself. Bitumen has migrated from areas where the Alum Shale is in close proxmity to Permo-Carboniferous intrusions, such as Halleberg-Hunneberg, into nearby areas such as Närke and ÖstergÖtland, where there is no evidence of intrusion and the indigenous organic matter is thermally immature. Other areas, where Alum Shales were associated with intrusions and consequently sourced oil, may have been eroded away. There are producing wells on the island of Gotland, where the Alum Shale is also thermally immature. It is therefore assumed that heating which was responsible for generating Gotland's oil was very localized (such as by an intrusion) or that the oil has migrated from a thermally moremature, distant area. On the basis of reservoir rock porosity, and the fact that the Alum Shale of Gotland contains no migrated component, localized heating is favored.     

Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease?

In an uncontrolled open study 13 patients with moderate to preterminal renal failure were treated with low doses (average 0.36 micrograms/day) of calcitriol up to the time of renal transplantation, which was performed before dialysis had been initiated. A transiliac bone biopsy was obtained both at the start and at the end of the treatment period, the latter coinciding with renal transplantation. All patients who started calcitriol treatment at a creatinine clearance (Ccr) above 30 ml/min had normal bone histology at the time of transplantation, but this was not observed when calcitriol treatment was started at Ccr below 30 ml/min. The study suggests that full benefit of calcitriol at the bone level is obtained only if prophylactic administration is started early in the course of renal failure.     

Yielding- and fracture behaviour of ferritic steels in the transition region of quasistatic to dynamic loading

This paper presents results of investigations on the influence of loading rate on yielding and fracture behaviour of ferritic steels. The range of loading rates was below a certain level at which a special stress wave analysis is required. Concerning the yielding behaviour it was found, that the yield strength can be predicted by the model of thermally activated flow. The strain hardening dσ/dε appeared to be independent of strain rate, if adiabetic heating can be neglected. Concerning the fracture behaviour it is demonstrated that the K_lc-T-curves are shifted to higher temperatures with increasing loading rate. The temperature shift could be correlated with the strain rate sensitivity m = d lnσ/d lnε. The ductile/brittle transition temperature increases with incrasing loading rate. For the upper shelf region crack resistance curves as a function of loading rate are presented. It is shown that the crack length can be determined using the key-curve-method. A slightly increasing tendency of the evaluated J_R-curves was found.