The Transient Receptor Potential Channel, Vanilloid 5, Induces Chondrocyte Apoptosis via Ca2+ CaMKII–Dependent MAPK and Akt/ mTOR Pathways in a Rat Osteoarthritis Model

Background/Aims: Chondrocyte apoptosis is a central pathological feature of cartilage in osteoarthritis (OA). Accumulating evidence suggests that calcium ions (Ca2+) are an important regulator of apoptosis. Previously, we reported that the transient receptor potential channel vanilloid (TRPV5) is upregulated in monoiodoacetic acid (MIA)-induced OA articular cartilage. Methods: The protein levels of TRPV5, phosphorylated Ca2+/calmodulin-dependent kinase II (p-CaMKII), and total CaMKII were detected in vivo using western blotting techniques. Primary chondrocytes were isolated and cultured in vitro. Then, p-CAMKII was immunolocalized by immunofluorescence in chondrocytes. Fluo-4AM staining was used to assess intracellular Ca2+. Annexin V-fluorescein isothiocyanate / propidium iodide flow cytometric analysis was performed to determine chondrocyte apoptosis. Western blotting techniques were used to measure the expression of apoptosis-related proteins. Results: We found that ruthenium red (aTRPV5inhibitor)or(1-[N,O-bis-(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperaze (KN-62) (an inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII) phosphorylation) can relieve or even reverse OA in vivo. We found that TRPV5 has a specific role in mediating extracellular Ca2+ influx leading to chondrocyte apoptosis in vitro. The apoptotic effect in chondrocytes was inhibited by KN-62. We found that activated p-CaMKII could elicit the phosphorylation of extracellular signal-regulated protein kinase 1/2, c-Jun N-terminal kinase, and p38, three important regulators of the mitogen-activated protein kinase (MAPK) cascade. Moreover, we also showed that activated p-CaMKII could elicit the phosphorylation of protein kinase B (Akt) and two important downstream regulators of mammalian target of rapamycin (mTOR): 4E-binding protein, and S61 kinase. Conclusion: Our results demonstrate that upregulated TRPV5 may be an important initiating factor that activates CaMKII phosphorylation via the mediation of Ca2+ influx. In turn, activated p-CaMKII plays a critical role in chondrocyte apoptosis via MAPK and Akt/mTOR pathways

Data-driven estimates of global nitrous oxide emissions from croplands

Croplands are the single largest anthropogenic source of nitrous oxide (N2O) globally, yet their estimates remain difficult to verify when using Tier 1 and 3 methods of the Intergovernmental Panel on Climate Change (IPCC). Here, we re-evaluate global cropland-N2O emissions in 1961–2014, using N-rate-dependent emission factors (EFs) upscaled from 1206 field observations in 180 global distributed sites and high-resolution N inputs disaggregated from sub-national surveys covering 15593 administrative units. Our results confirm IPCC Tier 1 default EFs for upland crops in 1990–2014, but give a ∼15% lower EF in 1961–1989 and a ∼67% larger EF for paddy rice over the full period. Associated emissions (0.82 ± 0.34 Tg N yr–1) are probably one-quarter lower than IPCC Tier 1 global inventories but close to Tier 3 estimates. The use of survey-based gridded N-input data contributes 58% of this emission reduction, the rest being explained by the use of observation-based non-linear EFs. We conclude that upscaling N2O emissions from site-level observations to global croplands provides a new benchmark for constraining IPCC Tier 1 and 3 methods. The detailed spatial distribution of emission data is expected to inform advancement towards more realistic and effective mitigation pathways

Cosmological Evolution of a Tachyon-Quintom Model of Dark Energy

In this work we study the cosmological evolution of a dark energy model with two scalar fields, i.e. the tachyon and the phantom tachyon. This model enables the equation of state $w$ to change from $w>-1$ to $w<-1$ in the evolution of the universe. The phase-space analysis for such a system with inverse square potentials shows that there exists a unique stable critical point, which has power-law solutions. In this paper, we also study another form of tachyon-quintom model with two fields, which voluntarily involves the interactions between both fields.Comment: 17 pages, 10 figure

Comparison of Early and Late Conversion of Sirolimus in Experimental Model of Chronic Cyclosporine Nephropathy

Sirolimus (SRL) is a promising drug for replacing calcineurin inhibitors. We performed this study to determine the optimal time of conversion from cyclosporine (CsA) to SRL in an experimental model of chronic CsA nephropathy. Three separate studies were performed. In the first study, SRL was given to rats with or without CsA for 4 weeks. In the second study, rats were treated initially with CsA for 1 week, and then switched to SRL (early conversion). In the third study, CsA was given for 4 weeks and then replaced by SRL for 4 weeks treatment of CsA (late conversion). The influence of SRL on CsA-induced renal injury was evaluated by assessing renal function, histopathology (interstitial inflammation and fibrosis), and apoptotic cell death. Combined CsA and SRL treatment significantly impaired renal function, increased apoptosis, and interstitial fibrosis and inflammation compared with CsA or SRL treatment alone. Early conversion to SRL did not change renal function, histopathology, or apoptosis compared with early CsA withdrawal. By contrast, late conversion to SRL significantly aggravated these parameters compared with late CsA withdrawal. In conclusion, early conversion from CsA to SRL is effective in preventing CsA-induced renal injury in a setting of CsA-induced renal injury

Extensive and drastically different alpine lake changes on Asia's high plateaus during the past four decades

Asia's high plateaus are sensitive to climate change and have been experiencing rapid warming over the past few decades. We found 99 new lakes and extensive lake expansion on the Tibetan Plateau during the last four decades, 1970–2013, due to increased precipitation and cryospheric contributions to its water balance. This contrasts with disappearing lakes and drastic shrinkage of lake areas on the adjacent Mongolian Plateau: 208 lakes disappeared, and 75% of the remaining lakes have shrunk. We detected a statistically significant coincidental timing of lake area changes in both plateaus, associated with the climate regime shift that occurred during 1997/1998. This distinct change in 1997/1998 is thought to be driven by large-scale atmospheric circulation changes in response to climate warming. Our findings reveal that these two adjacent plateaus have been changing in opposite directions in response to climate change. These findings shed light on the complex role of the regional climate and water cycles and provide useful information for ecological and water resource planning in these fragile landscapes.Publisher PDFPeer reviewe

Electric Field-Responsive Mesoporous Suspensions: A Review

This paper briefly reviews the fabrication and electrorheological (ER) characteristics of mesoporous materials and their nanocomposites with conducting polymers under an applied electric field when dispersed in an insulating liquid. Smart fluids of electrically-polarizable particles exhibit a reversible and tunable phase transition from a liquid-like to solid-like state in response to an external electric field of various strengths, and have potential applications in a variety of active control systems. The ER properties of these mesoporous suspensions are explained further according to their dielectric spectra in terms of the flow curve, dynamic moduli, and yield stress

Stimuli-Responsive Polymer-Clay Nanocomposites under Electric Fields

This short Feature Article reviews electric stimuli-responsive polymer/clay nanocomposites with respect to their fabrication, physical characteristics and electrorheological (ER) behaviors under applied electric fields when dispersed in oil. Their structural characteristics, morphological features and thermal degradation behavior were examined by X-ray diffraction pattern, scanning electron microscopy and transmission electron microscopy, and thermogravimetric analysis, respectively. Particular focus is given to the electro-responsive ER characteristics of the polymer/clay nanocomposites in terms of the yield stress and viscoelastic properties along with their applications