Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function

In protein folding and secretion disorders, activation of endoplasmic reticulum (ER) stress signaling (ERSS) protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs) during endochondral bone formation. In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del), misfolded alpha1(X) chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophic-like state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant collagen II and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia.

Evaluation of 15 mandibular reconstructions with Dumbach Titan Mesh-System and particulate cancellous bone and marrow harvested from bilateral posterior ilia

This study reports on 15 mandibular reconstructions using the Dumbach Titan Mesh-System and particulate cancellous bone and marrow harvested from bilateral posterior ilia. All cases showed segmental defects. Eleven cases involved patients with malignant tumor. Six patients had received irradiation of 40-50 Gy. Reconstructions were performed immediately in 1 patient and secondarily in the remaining 14 patients. In 13 cases, mandibles were successfully reconstructed. Of these 13 patients, 9 reconstructions were completed without complications, whereas the other 4 cases showed complications. In 2 cases, reconstruction failed completely. Overall success rate was 87%. Statistical analysis revealed the extent of mandibular defect, but not malignancy of the original disease or radiotherapy of

Measurement of Neutrino Oscillation Parameters from Muon Neutrino Disappearance with an Off-Axis Beam

The T2K collaboration reports a precision measurement of muon neutrino disappearance with an off-axis neutrino beam with a peak energy of 0.6 GeV. Near detector measurements are used to constrain the neutrino flux and cross section parameters. The Super-Kamiokande far detector, which is 295 km downstream of the neutrino production target, collected data corresponding to 3.01×1020 protons on target. In the absence of neutrino oscillations, 205±17 (syst.) events are expected to be detected and only 58 muon neutrino event candidates are observed. A fit to the neutrino rate and energy spectrum assuming three neutrino flavors, normal mass hierarchy and θ23≤π/4 yields a best-fit mixing angle sin2(2θ23)=1.000 and mass splitting |Δm232|=2.44×10−3 eV2/c4. If θ23≥π/4 is assumed, the best-fit mixing angle changes to sin2(2θ23)=0.999 and the mass splitting remains unchanged.

Observation of Electron Neutrino Appearance in a Muon Neutrino Beam

The T2K experiment has observed electron neutrino appearance in a muon neutrino beam produced 295 km from the Super-Kamiokande detector with a peak energy of 0.6 GeV. A total of 28 electron neutrino events were detected with an energy distribution consistent with an appearance signal, corresponding to a significance of 7.3σ when compared to 4.92 ± 0.55 expected background events. In the PMNS mixing model, the electron neutrino appearance signal depends on several parameters including three mixing angles θ12, θ23, θ13, a mass difference Δm232 and a CP violating phase δCP. In this neutrino oscillation scenario, assuming |Δm232|=2.4×10−3 eV2, sin2θ23=0.5, δCP=0, and Δm232>0 (Δm232<0), a best-fit value of sin22θ13 = 0.140+0.038−0.032 (0.170+0.045−0.037) is obtained.

IODP Expedition 337, Shimokita Deep Coalbed Biosphere

Microbial life inhabits deeply buried marine sediments, but the extent of this vast ecosystem remains poorly constrained. Here we provide evidence for the existence of microbial communities in ~40° to 60°C sediment associated with lignite coal beds at ~1.5 to 2.5 km below the seafloor in the Pacific Ocean off Japan. Microbial methanogenesis was indicated by the isotopic compositions of methane and carbon dioxide, biomarkers, cultivation data, and gas compositions. Concentrations of indigenous microbial cells below 1.5 km ranged from <10 to ~10**4 cells cm**-3. Peak concentrations occurred in lignite layers, where communities differed markedly from shallower subseafloor communities and instead resembled organotrophic communities in forest soils. This suggests that terrigenous sediments retain indigenous community members tens of millions of years after burial in the seabed.

Carbonate mineralogy and stable isotope composition of cool-water bryozoans from sediments of ODP Leg 182 sites

The carbon and oxygen isotopic compositions of selected bryozoan skeletons from upper Pleistocene bryozoan mounds in the Great Australian Bight (Ocean Drilling Program Leg 182; Holes 1129C, 1131A, and 1132B) were determined. Cyclostome bryozoans, Idmidronea spp. and Nevianipora sp., have low to intermediate magnesian calcite skeletons (1.5-10.0 and 0.9-6.4 molar percentage [mol%] MgCO3, respectively), but a considerable number include marine cements. The cheilostome Adeonellopsis spp. are biminerallic, principally aragonite, with some high magnesian calcite (HMC) (6.6-12.1 mol% MgCO3). The HMC fraction of Adeonellopsis has lower d13C and similar d18O values compared with the aragonite fraction. Reexamination of modern bryozoan isotopic composition shows that skeletons of Adeonellopsis spp. and Nevianipora sp. form close to oxygen isotopic equilibrium with their ambient water. Therefore, changes in glacial-interglacial oceanographic conditions are preserved in the oxygen isotopic profiles. The bryozoan oxygen isotopic profiles are correlated well with marine isotope Stages 1-8 in Holes 1129C and 1132B and to Stages 1-4(?) in Hole 1131A. The horizons of the bryozoan mounds that yield skeletons with heavier oxygen isotopic values can be correlated with isotope Stages 2, 4(?), 6, and 8 in Hole 1129C; Stages 2 and 4(?) in Hole 1131A; and Stages 2, 4, 6, and 8 in Hole 1132B. These results provide supporting evidence for a model for bryozoan mound formation, in which the mounds were formed during intensified upwelling and increased trophic resources during glacial periods.

Oxygen isotopes and hydrocarbon composition of gas hydrate and hydrate water from ODP Leg 165 sites

Ocean Drilling Program (ODP) Leg 164 recovered a number of large solid gas hydrate from Sites 994, 996, and 997 on the Blake Ridge. Sites 994 and 997 samples, either nodular or thick massive pieces, were subjected to laboratory analysis and measurements to determine the structure, molecular and isotopic composition, thermal conductivity, and equilibrium dissociation conditions. X-ray computed tomography (CT) imagery, X-ray diffraction, nuclear magnetic resonance (NMR), and Raman spectroscopy have revealed that the gas hydrates recovered from the Blake Ridge are nearly 100% methane gas hydrate of Structure I, cubic with a lattice constant of a = 11.95 ± 0.05 angström, and a molar ratio of water to gas (hydration number) of 6.2. The d18O of water is 2.67 per mil to 3.51 per mil SMOW, which is 3.5-4.0 heavier than the ambient interstitial waters. The d13C and dD of methane are -66 per mil to -70 per mil and -201 per mil to -206 per mil, respectively, suggesting that the methane was generated through bacterial CO2 reduction. Thermal conductivity values of the Blake Ridge hydrates range from 0.3 to 0.5 W/(m K). Equilibrium dissociation experiments indicate that the three-phase equilibrium for the specimen is 3.27 MPa at 274.7 K. This is almost identical to that of synthetic pure methane hydrate in freshwater.

Seawater carbonate chemistry and community calcification during Miyako Island (Japan) coral reef studies, 1994

Coral reefs are characterized by enormous carbonate production of the organisms. It is known that rapid calcification is linked to photosynthesis under control of the carbonate equilibrium in seawater. We have established a model simulating the coexisting states of photosynthesis and calcification in order to examine the effects of photosynthesis and calcification on the carbonate system in seawater. Supposing that the rates of photosynthesis and calcification are proportional to concentrations of their inorganic carbon source, the model calculations indicate that three kinds of unique interactions of the organic and inorganic carbon productions are expected. These are photosynthetic enhancement of calcification, calcification which benefits photosynthesis and carbonate dissolution induced by respiration. The first effect appears when the photosynthetic rate is more than approximately 1.2 larger than that of calcification. This effect is caused by the increase of CO3 content and carbonate saturation degree in seawater. If photosynthesis use molecular carbon dioxide, the second effect occurs when the calcification rate is more than approximately 1.6 times larger than that of photosynthesis. Time series model experiments indicate that photosynthesis and calcification potentially enhance each other and that organic and inorganic carbon is produced more efficiently in the coexisting system than in the isolated reactions. These coexisting effects on production enhancement of photosynthesis and calcification are expected to appear not only in the internal pool of organisms but also in a reef environment which is isolated from the outer ocean during low tide. According to the measurements on the fringing type Shiraho Reef in the Ryukyu Islands, the diurnal change of water properties (pH, total alkalinity, total carbon dioxide and carbonate saturation degree) were conspicuous. This environment offers an appropriate condition for the appearance of these coexisting effects. The photosynthetic enhancement of calcification and the respiratory inducement of decalcification were observed during day-time and night-time slack-water periods, respectively. These coexisting effects, especially the photosynthetic enhancement of calcification, appear to play important roles for fluorishing coral reef communities.