Copper deficit as a potential pathogenic factor of reduced bone mineral density and severe tooth wear

SUMMARY: The study evaluated if men and women with severe tooth wear were at increased risk of general bone loss. Enamel biopsies obtained from 50 subjects aged 47.5 ± 5 years showed decreased copper content, which was associated with reduced spine bone mineral density, suggesting deficits of this trace element contributing to bone demineralization, enamel attrition, and deteriorated quality of mineralized tissues. INTRODUCTION: The objective of this cross-sectional study was to assess associations between enamel trace minerals and bone mineral density (BMD) in severe tooth wear. We hypothesized that similar factors contributed to both the excessive abrasion of dental enamel and reduced BMD in subjects with tooth wear. METHODS: Fifty patients aged 47.5 ± 5 years with severe tooth wear and 20 age-, sex-, and body mass index (BMI)-matched healthy volunteers with normal dental status were studied regarding dietary intakes of trace elements, serum and salivary copper (Cu), zinc (Zn), and calcium (Ca) concentrations, and serum PTH, osteocalcin, and hydroxyvitamin D levels. Tooth wear was determined using clinical examination based on standard protocol according to Smith and Knight. In all subjects, acid biopsies of the maxillary central incisors were carried out to assess mineral composition of the enamel. Atomic absorption spectroscopy with an air/acetylene flame was used to measure Ca and Zn, and graphite furnace atomic absorption spectroscopy was used to analyze Cu content. BMD was examined using dual energy X-ray absorptiometry. RESULTS: Tooth wear patients had reduced lumbar spine, but not femoral, BMD relative to controls (p < 0.001). No differences were found in enamel Ca concentration and Zn content was slightly higher in tooth wear patients than in controls whereas Cu content was significantly decreased in the patients: 19.59 ± 16.4 vs 36.86 ± 26.1 μg/l (p = 0.01) despite similar levels of Cu in serum and saliva. The differences were independent of serum 25-OH-D, osteocalcin concentrations or PTH either. CONCLUSION: Severe tooth wear is associated with reduced spinal BMD. Enamel in adult individuals with severe tooth wear is low in copper content. Therefore, further work is needed to determine whether copper plays a role in bone pathophysiology in these patients

Relationship Between Masticatory Efficiency and Occlusal Parameters Established in T-Scan II System

The aim of this investigation was to establish possible correlation between parameters of occlusion and masticatory efficiency. MATERIAL: Data were obtained in 15 healthy persons, 23-31 years of age (mean 25 years) with correct own dentition and without any disturbances of the stomatognathic system. METHODS: Masticatory efficiency was measured using Optosil test modified by Slagter et al. after 20 and 80 cycles of chewing. It the time of chewing for 20 and 80 cycles of chewing was also established. Analysis of occlusion was made using T-scan II computerized system. Registration of occlusion was obtained before measuring masticatory efficiency after 20 and 80 cycles of chewing. Statistical analysis was made and p<0.05 was statistically significant. RESULTS: The time of chewing for 20 cycles and for 80 cycles respectively, mean 16 s +/- 3.0, and 55.6s +/- 9.5) reduction of particle size was about 1.5 mm. Time to maximal force ofpressure was shorter when chewing was longer. Maximal force of pressure for a unit of deflection indicator surface was higher after chewing. Share of sides of the teeth arch was about 59 per cent in all measurements. Maximal force of pressure for a unit of deflection indicator surface was correlated with the time of chewing for 20 cycles of chewing (p <0.05). Correlation of time from the first contact of teeth to maximal force of pressure and maximal force of pressure for a unit of deflection indicator surface was statistically significant for 80 cycles . There was no evident correlation between values of X50 and occlusal parameters established in computerizedanalysis. CONCLUSION: Chewing ability is correla ted with occlusion although this relationship is not significant

Syntaxin 8 regulates platelet dense granule secretion, aggregation, and thrombus stability.

Platelet secretion not only drives thrombosis and hemostasis, but also mediates a variety of other physiological and pathological processes. The ubiquitous SNARE machinery and a number of accessory proteins have been implicated in regulating secretion in platelet. Although several platelet SNAREs have been identified, further members of the SNARE family may be needed to fine-tune platelet secretion. In this study we identified expression of the t-SNARE syntaxin 8 (STX8) (Qc SNARE) in mouse and human platelets. In mouse studies, whereas STX8 was not essential for α-granule or lysosome secretion, Stx8(-/-) platelets showed a significant defect in dense granule secretion in response to thrombin and CRP. This was most pronounced at intermediate concentrations of agonists. They also showed an aggregation defect that could be rescued with exogenous ADP and increased embolization in Stx8(-/-) mice in vivo consistent with an important autocrine and paracrine role for ADP in aggregation and thrombus stabilization. STX8 therefore specifically contributes to dense granule secretion and represents another member of a growing family of genes that play distinct roles in regulating granule release from platelets and thus platelet function in thrombosis and hemostasis

New hints towards a precision medicine strategy for IDH wild-type glioblastoma.

Glioblastoma represents the most common primary malignancy of the central nervous system in adults and remains a largely incurable disease. The elucidation of disease subtypes based on mutational profiling, gene expression and DNA methylation has so far failed to translate into improved clinical outcomes. However, new knowledge emerging from the subtyping effort in the IDH-wild-type setting may provide directions for future precision therapies. Here, we review recent learnings in the field, and further consider how tumour microenvironment differences across subtypes may reveal novel contexts of vulnerability. We discuss recent treatment approaches and ongoing trials in the IDH-wild-type glioblastoma setting, and propose an integrated discovery stratagem incorporating multi-omics, single-cell technologies and computational approaches

An elastoplastic theory of dislocations as a physical field theory with torsion

We consider a static theory of dislocations with moment stress in an anisotropic or isotropic elastoplastical material as a T(3)-gauge theory. We obtain Yang-Mills type field equations which express the force and the moment equilibrium. Additionally, we discuss several constitutive laws between the dislocation density and the moment stress. For a straight screw dislocation, we find the stress field which is modified near the dislocation core due to the appearance of moment stress. For the first time, we calculate the localized moment stress, the Nye tensor, the elastoplastic energy and the modified Peach-Koehler force of a screw dislocation in this framework. Moreover, we discuss the straightforward analogy between a screw dislocation and a magnetic vortex. The dislocation theory in solids is also considered as a three-dimensional effective theory of gravity.Comment: 38 pages, 6 figures, RevTe

Tau Neutrinos Favored over Sterile Neutrinos in Atmospheric Muon Neutrino Oscillations

The previously published atmospheric neutrino data did not distinguish whether muon neutrinos were oscillating into tau neutrinos or sterile neutrinos, as both hypotheses fit the data. Using data recorded in 1100 live-days of the Super-Kamiokande detector, we use three complementary data samples to study the difference in zenith angle distribution due to neutral currents and matter effects. We find no evidence favoring sterile neutrinos, and reject the hypothesis at the 99% confidence level. On the other hand, we find that oscillation between muon and tau neutrinos suffices to explain all the results in hand.Comment: 9 pages with 2 figures, submitted to PR

Constraints on Neutrino Oscillations Using 1258 Days of Super-Kamiokande Solar Neutrino Data

We report the result of a search for neutrino oscillations using precise measurements of the recoil electron energy spectrum and zenith angle variations of the solar neutrino flux from 1258 days of neutrino-electron scattering data in Super-Kamiokande. The absence of significant zenith angle variation and spectrum distortion places strong constraints on neutrino mixing and mass difference in a flux-independent way. Using the Super-Kamiokande flux measurement in addition, two allowed regions at large mixing are found.Comment: 6 pages, 4 figures, submitted to PR

Solar 8B and hep Neutrino Measurements from 1258 Days of Super-Kamiokande Data

Solar neutrino measurements from 1258 days of data from the Super-Kamiokande detector are presented. The measurements are based on recoil electrons in the energy range 5.0-20.0MeV. The measured solar neutrino flux is 2.32 +- 0.03(stat.) +0.08-0.07(sys.)*10^6cm^{-2}s^{-1}, which is 45.1+-0.5(stat.)+1.6-1.4(sys.)% of that predicted by the BP2000 SSM. The day vs night flux asymmetry is 0.033+-0.022(stat.)+0.013-0.012(sys.). The recoil electron energy spectrum is consistent with no spectral distortion (\chi^2/d.o.f. = 19.0/18). The seasonal variation of the flux is consistent with that expected from the eccentricity of the Earth's orbit (\chi^2/d.o.f. = 3.7/7). For the hep neutrino flux, we set a 90% C.L. upper limit of 40 *10^3cm^{-2}s^{-1}, which is 4.3 times the BP2000 SSM prediction.Comment: 7 pages, 5 figures, submitted to PRL (part of this paper

Minnelide effectively eliminates CD133+ side population in pancreatic cancer

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) is a devastating disease hallmarked by limited patient survival. Resistance to chemotherapy, a major cause of treatment failure in PDAC patients, is often attributed to Cancer Stem Cells (CSCs). Pancreatic CSCs are a small subset of quiescent cells within a tumor represented by surface markers like CD133. These cells are responsible not only for tumor recurrence, but also poor prognosis based on their “stem-like” characteristics. At present, conventional therapy is directed towards rapidly dividing PDAC cells and thus fails to target the CSC population. METHODS: MIA PaCa-2, S2-013 and AsPC-1 were treated with 12.5 nM triptolide (12 T cells) for 7 days. The surviving cells were recovered briefly in drug-free growth media and then transferred to Cancer Stem cell Media (CSM). As a control, untreated cells were also transferred to CSM media (CSM). The 12 T and CSM cells were tested for stemness properties using RNA and protein markers. Low numbers of CSM and 12 T cells were implanted subcutaneously in athymic nude mice to study their tumorigenic potential. 12 T and CSM cells were sorted for CD133 expression and assayed for their colony forming ability and sphere forming ability. Invasiveness of 12 T cells, CSM and MIA PaCa-2 were compared using Boyden chamber assays. RESULTS: Treated 12 T cells displayed increased expression of the surface marker CD133 and the drug transporter ABCG2 compared to untreated cells (CSM cells). Both 12 T and CSM cells formed subcutaneous tumors in mice confirming their tumor-initiating properties. When tested for invasion, 12 T cells had increased invasiveness compared to CSM cells. CD133(+) cells in both CSM and 12 T showed greater colony and sphere forming ability compared to CD133(−) cells from each group. Consistent with these data, when injected subcutaneously in mice, CD133(−) cells from CSM or 12 T did not form any tumors whereas CD133(+) cells from both groups showed tumor formation at a very low cell number. Despite pre-exposure to triptolide in 12 T CD133(+) cells, treatment of tumors formed by these cells with Minnelide, a triptolide pro-drug, showed significant tumor regression. CONCLUSION: Our results indicated that triptolide enhanced and enriched the “stemness” in the PDAC cell lines at a low dose of 12.5 nM, but also resulted in the regression of tumors derived from these cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-015-0470-6) contains supplementary material, which is available to authorized users