Clay Mineralogy of Red Clay Deposits from the Central Carpathian Basin (Hungary): Implications for Plio/Pleistocene Chemical Weathering and Paleoclimate

Geochemical and mineralogical studies of palaeosols provide essential information for palaeoclimatic and palaeoenvironmental interpretation of continental deposits and can present a proxy for palaeoclimate. Red clays in the central Carpathian Basin (Hungary) (Tengelic Red Clay Formation; Kerecsend Red Clay Formation), overlain by loess-palaeosol sequences, were studied. Results from geochemical climofunctions applied to Upper Pliocene–Lower Pleistocene red clays and palaeosols located in the Carpathian Basin, and clay mineralogy, indicate that the palaeoclimate was considerably more humid and warmer during the Late Pliocene-Early Pleistocene in comparison to modern values

Thyroid hormones increase insulin-like growth factor mRNA levels in the clonal osteoblastic cell line MC3T3-E1

AbstractThyroid hormones are known to affect skeletal growth and maturation by influencing both bone resorption and bone formation. Their exact mechanism of action, however, is still unknown. Local factors such as prostaglandins, TGF-β or IGF-I were suggested to mediate their effects. Thyroid hormones were reported to stimulate expression of IGF-I mRNA in liver and kidney and to increase IGF-I release from bone organ cultures and osteoblast-like cells. Therefore we studied the effect of thyroid hormones on IGF-I mRNA expression in MC3T3-E1 cells. The cells were grown in culture for 5 to 7 days and treated with triiodothyronine (10−11 - 10−6 M) and thyroxin (10−6 M) for 1–24 h. Cellular mRNA was isolated and subjected to Northern hybridization. The amount of IGF-I mRNA, which is already expressed in this cell line under control conditions, was markedly enhanced by T3 and T4. This effect was found to be dose-dependent with a maximum at 10−7M and could already be seen after 3 h increasing up to 24 h. Our findings indicate that IGF-I expression in osteoblasts is directly regulated by thyroid hormones. We conclude that IGF-I expression belongs to the phenotypic characteristics of mature osteoblasts, and that thyroid hormones play an important role in differentiation of MC3T3-E1 cells along the osteoblastic lineage

Distinctive spinal changes in two patients with unusual forms of autosomal dominant endosteal hyperostosis: a case series

Endosteal hyperostosis was encountered in a 26-year-old-man and his 6-month-old daughter. Both the father and his daughter presented with fractures. Odontoid process hyperplasia, and progressive sclerosis of the posterior spinal elements, was the other significant features. To the best of our knowledge, this is the first clinical report describing distinctive spinal changes in association with fractures and endosteal hyperostosis

Generation of a Highly Active Folding Enzyme by Combining a Parvulin-Type Prolyl Isomerase from SurA with an Unrelated Chaperone Domain

AbstractParvulins are small prolyl isomerases and serve as catalytic domains of folding enzymes. SurA (survival protein A) from the periplasm of Escherichia coli consists of an inactive (Par1) and an active (Par2) parvulin domain as well as a chaperone domain. In the absence of the chaperone domain, the folding activity of Par2 is virtually abolished. We created a chimeric protein by inserting the chaperone domain of SlyD, an unrelated folding enzyme from the FKBP family, into a loop of the isolated Par2 domain of SurA. This increased its folding activity 450-fold to a value higher than the activity of SurA, in which Par2 is linked with its natural chaperone domain. In the presence of both the natural and the foreign chaperone domain, the folding activity of Par2 was 1500-fold increased. Related and unrelated chaperone domains thus are similarly efficient in enhancing the folding activity of the prolyl isomerase Par2. A sequence analysis of various chaperone domains suggests that clusters of exposed methionine residues in mobile chain regions might be important for a generic interaction with unfolded protein chains. This binding is highly dynamic to allow frequent transfer of folding protein chains between chaperone and catalytic domains

Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells

The mevalonate pathway provides metabolites for post-translational modifications such as farnesylation, which are critical for the activity of RAS downstream signaling. Subsequently occurring regulatory processes can induce an aberrant stimulation of DNA methyltransferase (DNMT1) as well as changes in histone deacetylases (HDACs) and microRNAs in many cancer cell lines. Inhibitors of the mevalonate pathway are increasingly recognized as anticancer drugs. Extensive evidence indicates an intense cross-talk between signaling pathways, which affect growth, differentiation, and apoptosis either directly or indirectly via epigenetic mechanisms. Herein, we show data obtained by novel transcriptomic and corresponding methylomic or proteomic analyses from cell lines treated with pharmacologic doses of respective inhibitors (i.e., simvastatin, ibandronate). Metabolic pathways and their epigenetic consequences appear to be affected by a changed concentration of NADPH. Moreover, since the mevalonate metabolism is part of a signaling network, including vitamin D metabolism or fatty acid synthesis, the epigenetic activity of associated pathways is also presented. This emphasizes the far-reaching epigenetic impact of metabolic therapies on cancer cells and provides some explanation for clinical observations, which indicate the anticancer activity of statins and bisphosphonates

Analytical Strategies for the Determination of Deoxynivalenol and its Modified Forms in Beer: A Mini Review

The aim of this review is to provide a brief overview of analytical methods used for the determination of deoxynivalenol and its modified forms deoxynivalenol-3-β-D-glucoside, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol in beer. The analytical methods discussed involve gas chromatography coupled with flame ionization detection, electron capture detection and mass spectrometry as well as liquid chromatography hyphenated to ultra-violet detection and mass spectrometry. Special attention was paid to sample preparation. Immunochemical methods such as enzyme-linked immunosorbent assays (ELISAs) which represent efficient tools for fast screening of beer with no sample purification are also discussed

A Novel Technique for Treatment of Metaphyseal Voids in Proximal Humerus Fractures in Elderly Patients

Background and Objectives: The treatment of proximal humerus fractures in elderly patients is challenging, with reported high complication rates mostly related to implant failure involving screw cut-out and penetration. Metaphyseal defects are common in osteoporotic bone and weaken the osteosynthesis construct. A novel technique for augmentation with polymethylmethacrylate (PMMA) bone cement was developed for the treatment of patients in advanced age with complex proximal humerus fractures and metaphyseal voids, whereby the cement was allowed to partially cure for 5-7 min after mixing to achieve medium viscosity, and then it was manually placed into the defect through the traumatic lateral window with a volume of 4-6 mL per patient. The aim of this retrospective clinical study was to assess this technique versus autologous bone graft augmentation and no augmentation. Materials and Methods: The outcomes of 120 patients with plated Neer three- and four-part fractures, assigned to groups of 63 cases with no augmentation, 28 with bone graft augmentation and 29 with cement augmentation, were assessed in this study. DASH, CS, pain scores and range of motion were analyzed at 3, 6 and 12 months. Statistical analysis was performed with factors for treatment and age groups, Neer fracture types and follow-up periods, and with the consideration of age as a covariate. Results: DASH and CS improved following cement augmentation at three and six months compared to bone grafting, being significant when correcting for age as a covariate (p ≤ 0.007). While the age group had a significant effect on both these scores with worsened values at a higher age for non-augmented and grafted patients (p ≤ 0.044), this was not the case for cement augmented patients (p ≥ 0.128). Cement augmentation demonstrated good clinical results at 12 months with a mean DASH of 10.21 and mean CS percentage of 84.83% versus the contralateral side, not being significantly different among the techniques (p ≥ 0.372), despite the cement augmented group representing the older population with more four-part fractures. There were no concerning adverse events specifically related to the novel technique. Conclusions: This study has detailed a novel technique for the treatment of metaphyseal defects with PMMA cement augmentation in elderly patients with complex proximal humerus fractures and follow-up to one year, whereby the cement was allowed to partially cure to achieve medium viscosity, and then it was manually placed into the defect through the traumatic lateral window. The results demonstrate clinically equivalent short-term results to 6 months compared to augmentation with bone graft or no augmentation-despite the patient group being older and with a higher rate of more severe fracture patterns. The technique appears to be safe with no specifically related adverse events and can be added in the surgeon's armamentarium for the treatment of these difficult to manage fractures