Tibetan Plateau uplift has been suggested as the main driving force for mid-latitude Asian inland aridity (AIA) and for deposition of thick aeolian sequences in northern China since the Miocene. ...However, the relationship between earlier AIA and Tibetan Plateau mountain building is uncertain because of a lack of corresponding thick aeolian sequences with accurate age constraints. We here present results for a continuous aeolian sequence that spans the interval from >51 to 39 Ma from the eastern Xorkol Basin, Altun Shan, northeastern Tibetan Plateau. The basal age of the studied sequence postdates initial uplift of the Tibetan Plateau by several million years. Our results indicate that the local palaeoclimate was teleconnected strongly to the overall global cooling pattern, so that local enhanced aridification recorded by the studied aeolian sequence is dominantly a response to global climatic forcing rather than plateau uplift.
Summary
Activated acid-sensing ion channel 1a (ASIC1a) is involved in acid-induced osteoclastogenesis by regulating activation of the transcription factor NFATc1. These results indicated that ASIC1a ...activation by extracellular acid may cause osteoclast migration and adhesion through Ca
2+
-dependent integrin/Pyk2/Src signaling pathway.
Introduction
Osteoclast adhesion and migration are responsible for osteoporotic bone loss. Acidic conditions promote osteoclastogenesis. ASIC1a in osteoclasts is associated with acid-induced osteoclastogenesis through modulating transcription factor NFATc1 activation. However, the influence and the detailed mechanism of ASIC1a in regulating osteoclast adhesion and migration, in response to extracellular acid, are not well characterized.
Methods
In this study, knockdown of ASIC1a was achieved in bone marrow macrophage cells using small interfering RNA (siRNA). The adhesion and migration abilities of osteoclast precursors and osteoclasts were determined by adhesion and migration assays, in vitro. Bone resorption was performed to measure osteoclast function. Cytoskeletal changes were assessed by F-actin ring formation. αvβ3 integrin expression in osteoclasts was measured by flow cytometry. Western blotting and co-immunoprecipitation were performed to measure alterations in integrin/Pyk2/Src signaling pathway.
Results
Our results showed that blockade of ASIC1a using ASIC1a-siRNA inhibited acid-induced osteoclast precursor migration and adhesion, as well as osteoclast adhesion and bone resorption; we also demonstrated that inhibition of ASIC1a decreased the cell surface αvβ3 integrin and β3 protein expression. Moreover, blocking of ASIC1a inhibited acidosis-induced actin ring formation and reduced Pyk2 and Src phosphorylation in osteoclasts and also inhibited the acid-induced association of the αvβ3 integrin/Src/Pyk2.
Conclusion
Together, these results highlight a key functional role of ASIC1a/αvβ3 integrin/Pyk2/Src signaling pathway in migration and adhesion of osteoclasts.
Spontaneous ignition of compressed hydrogen release through a length of tube with different internal geometries is numerically investigated using our previously developed model. Four types of ...internal geometries are considered: local contraction, local enlargement, abrupt contraction and abrupt enlargement. The presence of internal geometries was found to significantly increase the propensity to spontaneous ignition. Shock reflections from the surfaces of the internal geometries and the subsequent shock interactions further increase the temperature of the combustible mixture at the contact region. The presence of the internal geometry stimulates turbulence enhanced mixing between the shock-heated air and the escaping hydrogen, resulting in the formation of more flammable mixture. It was also found that forward-facing vertical planes are more likely to cause spontaneous ignition by producing the highest heating to the flammable mixture than backward-facing vertical planes.
A feeding trial was conducted to investigate the effects of dietary fructooligosaccharide (FOS) on growth performance, body composition, intestinal enzymes activities and histology of fingerling ...Megalobrama amblycephala. A total of 1200 fish (1.42 ± 0.01 g) were fed diets containing graded levels of FOS (0, 0.5, 1, 2, 4 and 8 g kg−1 diet) for 8 weeks in a recirculating system indoor. The weight gain, specific growth rate (SGR) and survival rate were all improved in dietary supplementation of FOS fed fish. Increasing FOS levels resulted in both higher whole‐body lipid and lower moisture contents, whereas ash and protein contents showed no significant differences among all the treatments. Intestinal amylase, protease, Na+, K+‐ATPase, alkaline phosphatase, γ‐glutamyl transpeptidase and creatine kinase activities all increased with dietary FOS levels up to 4 g kg−1 (P < 0.05). Transmission electron microscopy analysis indicated that microvilli length in the mid‐intestine was significantly increased with increased dietary FOS levels (P < 0.05). In conclusion, dietary supplementation of FOS could confer benefits on growth performance, intestinal digestive and absorptive ability, histology of fingerling Megalobrama amblycephala.
The iron-based superconductors are characterized by multiple-orbital physics where all the five Fe3dorbitals get involved. The multiple-orbital nature gives rise to various novel phenomena like ...orbital-selective Mott transition, nematicity, and orbital fluctuation that provide a new route for realizing superconductivity. The complexity of multiple-orbital physics also requires us to disentangle the relationship between orbital, spin, and nematicity, and to identify dominant orbital ingredients that dictate superconductivity. The bulk FeSe superconductor provides an ideal platform to address these issues because of its simple crystal structure and unique coexistence of superconductivity and nematicity. However, the orbital nature of the low-energy electronic excitations and its relation to the superconducting gap remain controversial. Here, we report direct observation of the highly anisotropic Fermi surface and extremely anisotropic superconducting gap in the nematic state of the FeSe superconductor by high-resolution laser-based angle-resolved photoemission measurements. We find that the low-energy excitations of the entire hole pocket at the Brillouin zone center are dominated by the singledxzorbital. The superconducting gap exhibits an anticorrelation relation with thedxzspectral weight near the Fermi level; i.e., the gap size minimum (maximum) corresponds to the maximum (minimum) of thedxzspectral weight along the Fermi surface. These observations provide new insights in understanding the orbital origin of the extremely anisotropic superconducting gap in the FeSe superconductor and the relation between nematicity and superconductivity in the iron-based superconductors.
Copy number variation (CNV) is an important source of genetic variation in organisms and a main factor that affects phenotypic variation. A comprehensive study of chicken CNV can provide valuable ...information on genetic diversity and facilitate future analyses of associations between CNV and economically important traits in chickens. In the present study, an F2 full-sib chicken population (554 individuals), established from a cross between Xinghua and White Recessive Rock chickens, was used to explore CNV in the chicken genome. Genotyping was performed using a chicken 60K SNP BeadChip. A total of 1,875 CNV were detected with the PennCNV algorithm, and the average number of CNV was 3.42 per individual. The CNV were distributed across 383 independent CNV regions (CNVR) and covered 41 megabases (3.97%) of the chicken genome. Seven CNVR in 108 individuals were validated by quantitative real-time PCR, and 81 of these individuals (75%) also were detected with the PennCNV algorithm. In total, 274 CNVR (71.54%) identified in the current study were previously reported. Of these, 147 (38.38%) were reported in at least 2 studies. Additionally, 109 of the CNVR (28.46%) discovered here are novel. A total of 709 genes within or overlapping with the CNVR was retrieved. Out of the 2,742 quantitative trait loci (QTL) collected in the chicken QTL database, 43 QTL had confidence intervals overlapping with the CNVR, and 32 CNVR encompassed one or more functional genes. The functional genes located in the CNVR are likely to be the QTG that are associated with underlying economic traits. This study considerably expands our insight into the structural variation in the genome of chickens and provides an important resource for genomic variation, especially for genomic structural variation related to economic traits in chickens.
Radiochemoresistance is considered the main cause of local recurrence and distant metastasis in lung cancer. However, the underlying mechanisms of radiochemoresistance remain to be uncovered. In this ...study, we determine the functions of cell cycle-related kinase (CDK20) in radiochemoresistance. CDK20 is a newly identified protein kinase, which plays critical roles in cell growth and proliferation in several types of cancer. Using tandem affinity purification technology, we provide evidences that CDK20 binds to the ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1), which targets transcriptional factor nuclear factor erythroid-2-related factor 2 (NRF2) for degradation. We show that this interaction is mediated by an evolutionarily conserved ETGE motif on CDK20. Furthermore, we demonstrate that CDK20 competes with NRF2 for KEAP1 binding, enhances the transcriptional activity of NRF2 and lowers the cellular reactive oxygen species level. Moreover, CDK20-depleted cells display impaired cell proliferation, defective G2/M arrest and increased radiochemosensitivity in lung cancer. These phenotypes induced by CDK20 knockdown are partially dependent on NRF2 inactivation. More importantly, CDK20 is overexpressed in human lung cancer tissues, as determined by immunostaining. Collectively, our results suggest that CDK20 positively modulate the KEAP1-NRF2 cytoprotective pathway to regulate tumor progression and radiochemoresistance, implying that CDK20 is a novel, promising therapeutic target for lung cancer.
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