The Mekong Basin has remained relatively intact, but the current plans for rapid development in the hydropower sector may threaten the riverine ecosystems. Should all the plans be materialized in ...tributaries and mainstream, the cumulative active storage capacity of the reservoirs would increase more than tenfold from the present level to around 20% of the annual discharge of the Mekong (505
km
3). In this study a protocol is developed to estimate the trapping efficiency (
TE) of the existing and planned reservoirs in the Mekong Basin based on Brune's method. The existing reservoirs have a basin
TE of 15–18% and should all the planned reservoirs be built, this will increase to 51–69%. However, due to the high heterogeneity of the specific sediment yield in different parts of the basin, the trapped sediment load (
TSL) is predicted to be much higher. The existing and planned mainstream dams in the Chinese part of the river have the largest impact on the river sediment load (
SL) as more than 60% of the basin
SL originates from this stretch of the river. The three existing reservoirs in that part of the basin have potential to trap annually approximately 32–41
Mt of sediment. If the entire cascade of eight dams is constructed,
TE will increase to 78–81%, and potentially 70–73
Mt, i.e. more than 50% of the total basin sediment load (∼
140
Mt) will be trapped annually.
Nanog is a transcription factor required for maintaining the pluripotency of embryonic stem cells, and is not expressed in most normal adult tissues. However, recent studies have indicated that Nanog ...is overexpressed in many types of human cancers, including breast cancer. To elucidate the physiological roles of Nanog in tumorigenesis, we developed an inducible Nanog transgenic mouse model, in which the expression of Nanog in adult tissues can be induced via LoxP/Cre-mediated deletion. Our findings indicate that overexpression of Nanog in the mammary gland is not sufficient to induce mammary tumor. However, when coexpressed with Wnt-1 in the mouse mammary gland, it promotes mammary tumorigenesis and metastasis. In this context, Nanog promotes the migration and invasion of breast cancer cells. Microarray analysis has shown that the ectopic expression of Nanog deregulates the expression of numerous genes associated with tumorigenesis and metastasis, such as the PDGFRα gene. Our findings demonstrate the involvement of Nanog in breast cancer metastasis, and provide the basis for the reported correlation between Nanog expression and poor prognosis of human breast cancer patients. As Nanog is not expressed in most adult tissues, these findings identify Nanog as a potential therapeutic target in the treatment of Nanog-expressing metastatic breast cancer.
Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of ...OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox). These mice developed early cartilage degeneration at 6 mo of age. By 2 mo of age, although their gross cartilage morphology appears normal, CKO mice had a drastically reduced number of superficial chondrocytes and decreased lubricant secretion at the surface. Using superficial chondrocyte and cartilage explant cultures, we demonstrated that EGFR signaling is critical for maintaining the number and properties of superficial chondrocytes, promoting chondrogenic proteoglycan 4 (Prg4) expression, and stimulating the lubrication function of the cartilage surface. In addition, EGFR deficiency greatly disorganized collagen fibrils in articular cartilage and strikingly reduced cartilage surface modulus. After surgical induction of OA at 3 mo of age, CKO mice quickly developed the most severe OA phenotype, including a complete loss of cartilage, extremely high surface modulus, subchondral bone plate thickening, and elevated joint pain. Taken together, our studies establish EGFR signaling as an important regulator of the superficial layer during articular cartilage development and OA initiation.
Allergic airway inflammation is characterized by marked in situ changes in gene and protein expression, yet the role of microRNAs (miRNAs), a new family of key mRNA regulatory molecules, in this ...process has not yet been reported. Using a highly sensitive microarray-based approach, we identified 21 miRNAs with differential expression between doxycycline-induced lung-specific IL-13 transgenic mice (with allergic airway inflammation) and control mice. In particular, we observed overexpression of miR-21 and underexpression of miR-1 in the induced IL-13 transgenic mice compared with control mice. These findings were validated in two independent models of allergen-induced allergic airway inflammation and in IL-4 lung transgenic mice. Although IL-13-induced miR-21 expression was IL-13Ralpha1 dependent, allergen-induced miR-21 expression was mediated mainly independent of IL-13Ralpha1 and STAT6. Notably, predictive algorithms identified potential direct miR-21 targets among IL-13-regulated lung transcripts, such as IL-12p35 mRNA, which was decreased in IL-13 transgenic mice. Introduction of pre-miR-21 dose dependently inhibited cellular expression of a reporter vector harboring the 3'-untranslated region of IL-12p35. Moreover, mutating miR-21 binding sites in IL-12p35 3'-untranslated region abrogated miR-21-mediated repression. In summary, we have identified a miRNA signature in allergic airway inflammation, which includes miR-21 that modulates IL-12, a molecule germane to Th cell polarization.
ABSTRACTIntracellular calcium (Ca2+i) oscillation is a fundamental signaling response of cartilage cells under mechanical loading or osmotic stress. Chondrocytes are usually considered as ...nonexcitable cells with no spontaneous Ca2+i signaling. This study proved that chondrocytes can exhibit robust spontaneous Ca2+i signaling without explicit external stimuli. The intensity of Ca2+i peaks from individual chondrocytes maintain a consistent spatiotemporal pattern, acting as a unique “fingerprint” for each cell. Statistical analysis revealed lognormal distributions of the temporal parameters of Ca2+i peaks, as well as strong linear correlations between their means and sds. Based on these statistical findings, we hypothesized that the spontaneous Ca2+i peaks may result from an autocatalytic process and that Ca2+i oscillation is controlled by a threshold‐regulating mechanism. To test these 2 mechanisms, we established a multistage biophysical model by assuming the spontaneous Ca2+i signaling of chondrocytes as a combination of deterministic and stochastic processes. The theoretical model successfully explained the lognormal distribution of the temporal parameters and the fingerprint feature of Ca2+i peaks. In addition, by using antagonists for 10 pathways, we revealed that the initiation of spontaneous Ca2+i peaks in chondrocytes requires the presence of extracellular Ca2+, and that the PLC‐inositol 1,4,5‐trisphosphate pathway, which controls the release of calcium from the endoplasmic reticulum, can affect the initiation of spontaneous Ca2+i peaks in chondrocytes. The purinoceptors and transient receptor potential vanilloid 4 channels on the plasma membrane also play key roles in the spontaneous Ca2+i signaling of chondrocytes. In contrast, blocking the T‐type or L‐type voltage‐gated calcium channel promoted the spontaneous calcium signaling. This study represents a systematic effort to understand the features and initiation mechanisms of spontaneous Ca2+i signaling in chondrocytes, which are critical for chondrocyte mechanobiology.—Zhou, Y., Lv, M., Li, T., Zhang, T., Duncan, R., Wang, L., Lu, X. L. Spontaneous calcium signaling of cartilage cells: from spatiotemporal features to biophysical modeling. FASEB J. 33, 4675–4687 (2019). www.fasebj.org
Context. The submillimeter spectral domain has been extensively explored by the Herschel and Planck satellites and is now reachable from the ground with ALMA. A wealth of data, revealing cold dust ...thermal emission, is available for astronomical environments ranging from interstellar clouds, cold clumps, circumstellar envelops, and protoplanetary disks. The interpretation of these observations relies on the understanding and modeling of cold dust emission and on the knowledge of the dust optical properties. Aims. The aim of this work is to provide astronomers with a set of spectroscopic data of realistic interstellar dust analogues that can be used to interpret the observations. It pursues the experimental effort aimed at characterizing the spectroscopic properties of interstellar dust analogues at low temperature in the mid-infrared (MIR) to millimeter spectral domain. Compared to previous studies, it extends the range of studied dust analogues in terms of composition and of structure of the material. Methods. Glassy silicates of mean composition (1-x)MgO - x SiO sub(2) with x= 0.35 (close to forsterite, Mg sub(2) SiO sub(4)), 0.50 (close to enstatite, MgSiO sub(3)) and 0.40 (close to Mg sub(1.5) SiO sub(3.5) or MgSiO sub(3):Mg sub(2) SiO sub(4)= 50:50) were synthesized. The mass absorption coefficient (MAC) of the samples was measured in the spectral domain 30-1000 mu m for grain temperature in the range 300-10 K and at room temperature in the 5-40 mu m domain. Results. We find that the MAC of all samples varies with the grains temperature and that its spectral shape cannot be approximated by a single power law in lambda super(- beta). In the FIR/submm, and above 30 K, the MAC value at a given wavelength increases with the temperature as thermally activated absorption processes appear. The studied materials exhibit different and complex behaviors at long wavelengths (lambda> or = 200 to 700 mu m depending on the samples). These behaviors are attributed to the amorphous nature of dust and to the amount and nature of the defects within this amorphous structure. We do not observe MAC variations in the 10-30 K range. Above 20 mu m, the measured MAC are much higher than the MAC calculated from interstellar silicate dust models indicating that the analogues measured in this study are more emissive than the silicates in cosmic dust models. Conclusions. The underestimated value of the MAC deduced from cosmic dust models in the FIR/submm has important astrophysical implications because masses are overestimated by the models. Moreover, constraints on elemental abundance of heavy elements in cosmic dust models are relaxed.
Iron selenide superconductors exhibit a number of unique characteristics that are helpful for understanding the mechanism of superconductivity in high-Tc iron-based superconductors more generally. ...However, in the case of AxFe2Se2 (A = K, Rb, Cs), the presence of an intergrown antiferromagnetic insulating phase makes the study of the underlying physics problematic. Moreover, FeSe-based systems intercalated with alkali metal ions, NH3 molecules or organic molecules are extremely sensitive to air, which prevents the further investigation of their physical properties. It is therefore desirable to find a stable and easily accessible FeSe-based superconductor to study its physical properties in detail. Here, we report the synthesis of an air-stable material, (Li0.8Fe0.2)OHFeSe, which remains superconducting at temperatures up to ~40 K, by means of a novel hydrothermal method. The crystal structure is unambiguously determined by a combination of X-ray and neutron powder diffraction and nuclear magnetic resonance. Moreover, antiferromagnetic order is shown to coexist with superconductivity. This synthetic route opens a path for exploring superconductivity in other related systems, and confirms the appeal of iron selenides as a platform for understanding superconductivity in iron pnictides more broadly.
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