The effect of participation in ecological public welfare positions on farmers' household income composition and the internal mechanism

peer reviewe

Critical role of PIP5KIγ87 in InsP3-mediated Ca2+ signaling

Phosphatidylinositol 4,5-bisphosphate (PIP2) is the obligatory precursor of inositol 1,4,5-trisphosphate (InsP3 or IP3) and is therefore critical to intracellular Ca2+ signaling. Using RNA interference (RNAi), we identified the short splice variant of type I phosphatidylinositol 4-phosphate 5-kinase γ (PIP5KIγ87) as the major contributor of the PIP2 pool that supports G protein–coupled receptor (GPCR)-mediated IP3 generation. PIP5KIγ87 RNAi decreases the histamine-induced IP3 response and Ca2+ flux by 70%. Strikingly, RNAi of other PIP5KI isoforms has minimal effect, even though some of these isoforms account for a larger percent of total PIP2 mass and have previously been implicated in receptor mediated endocytosis or focal adhesion formation. Therefore, PIP5KIγ87's PIP2 pool that supports GPCR-mediated Ca2+ signaling is functionally compartmentalized from those generated by the other PIP5KIs

Association between alcohol consumption during pregnancy and risks of congenital heart defects in offspring: Meta-analysis of epidemiological observational studies

BACKGROUND: To explore the association between maternal alcohol consumption and/or binge drinking and congenital heart defects (CHDs), we conducted a meta-analysis for more sufficient evidence on this issue. METHODS: We searched Medline, EMBASE, and the Cochrane Library from their inceptions to December 2014 for case-control and cohort studies that assessed the association between maternal alcohol consumption and CHD risk. Study-specific relative risk estimates were calculated using random-effect or fixed-effect models. RESULTS: A total of 19 case-control studies and 4 cohort studies were included in the meta-analysis. We observed a null association between maternal alcohol consumption during pregnancy and the risk of CHDs. Even in the analysis of different trimesters of pregnancy, we found little association between the two. CONCLUSIONS: This meta-analysis suggests that maternal alcohol consumption is modestly not associated with the risk of CHDs. However, further investigation is needed to confirm this conclusion

Endothelium- targeted overexpression of Krüppel- like factor 11 protects the blood- brain barrier function after ischemic brain injury

Microvascular endothelial cell (EC) injury and the subsequent blood- brain barrier (BBB) breakdown are frequently seen in many neurological disorders, including stroke. We have previously documented that peroxisome proliferator- activated receptor gamma (PPARγ)- mediated cerebral protection during ischemic insults needs Krüppel- like factor 11 (KLF11) as a critical coactivator. However, the role of endothelial KLF11 in cerebrovascular function and stroke outcome is unclear. This study is aimed at investigating the regulatory role of endothelial KLF11 in BBB preservation and neurovascular protection after ischemic stroke. EC- targeted overexpression of KLF11 significantly mitigated BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and infiltration of peripheral immune cells, and less brain water content. Endothelial cell- selective KLF11 transgenic (EC- KLF11 Tg) mice also exhibited smaller brain infarct and improved neurological function in response to ischemic insults. Furthermore, EC- targeted transgenic overexpression of KLF11 preserved cerebral tight junction (TJ) levels and attenuated the expression of pro- inflammatory factors in mice after ischemic stroke. Mechanistically, we demonstrated that KLF11 directly binds to the promoter of major endothelial TJ proteins including occludin and ZO- 1 to promote their activities. Our data indicate that KLF11 functions at the EC level to preserve BBB structural and functional integrity, and therefore, confers brain protection in ischemic stroke. KLF11 may be a novel therapeutic target for the treatment of ischemic stroke and other neurological conditions involving BBB breakdown and neuroinflammation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155919/1/bpa12831_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155919/2/bpa12831.pd

Detection of the circulating antigen 14-3-3 protein of Schistosoma japonicum by time-resolved fluoroimmunoassay in rabbits

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis remains a major public health concern that afflicts millions of people worldwide. Low levels of <it>Schistosoma </it>infection require more sensitive diagnostic methods. In this study, a time-resolved fluoroimmunoassay (TRFIA) was developed for detecting the signal transduction protein 14-3-3, a circulating antigen of <it>Schistosoma japonicum</it>.</p> <p>Results</p> <p>The detection limit of 14-3-3-TRFIA was 0.78 ng/ml, with a linear measurement range from 0.78 to 800 ng/ml. The average intra-assay and inter-assay variability of this TRFIA was 8.9% and 12.2% respectively, and the mean recovery rate ranged from 92.1% to 115.5%. Within the first 21 days post-infection in rabbits, the positive rates of the 14-3-3-TRFIA were distinctly higher compared to ELISA. All these findings illustrate that 14-3-3-TRFIA has a higher detection efficacy and is a good early diagnostic method for active <it>Schistosoma </it>infection.</p> <p>Conclusions</p> <p>A sandwich TRFIA for detecting the circulating antigen 14-3-3 of <it>S. japonicum </it>has been developed, and has demonstrated to be a good potential diagnostic method for schistosomiasis.</p

Physical properties and chemical composition of the cores in the California molecular cloud

We aim to reveal the physical properties and chemical composition of the cores in the California molecular cloud (CMC), so as to better understand the initial conditions of star formation. We made a high-resolution column density map (18.2") with Herschel data, and extracted a complete sample of the cores in the CMC with the \textsl{fellwalker} algorithm. We performed new single-pointing observations of molecular lines near 90 GHz with the IRAM 30m telescope along the main filament of the CMC. In addition, we also performed a numerical modeling of chemical evolution for the cores under the physical conditions. We extracted 300 cores, of which 33 are protostellar and 267 are starless cores. About 51\% (137 of 267) of the starless cores are prestellar cores. Three cores have the potential to evolve into high-mass stars. The prestellar core mass function (CMF) can be well fit by a log-normal form. The high-mass end of the prestellar CMF shows a power-law form with an index $\alpha=-0.9\pm 0.1$ that is shallower than that of the Galactic field stellar mass function. Combining the mass transformation efficiency ($\varepsilon$) from the prestellar core to the star of $15\pm 1\%$ and the core formation efficiency (CFE) of 5.5\%, we suggest an overall star formation efficiency of about 1\% in the CMC. In the single-pointing observations with the IRAM 30m telescope, we find that 6 cores show blue-skewed profile, while 4 cores show red-skewed profile. [$\rm {HCO}^{+}$]/[HNC] and [$\rm {HCO}^{+}$]/$\rm [N_{2}H^{+}]$ in protostellar cores are higher than those in prestellar cores; this can be used as chemical clocks. The best-fit chemical age of the cores with line observations is $\sim 5\times 10^4$~years.Comment: Accepted by Astronomy & Astrophysics (A&A

Monitoring specific antibody responses against the hydrophilic domain of the 23 kDa membrane protein of Schistosoma japonicum for early detection of infection in sentinel mice

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis remains an important public health problem throughout tropical and subtropical countries. Humans are infected through contact with water contaminated with schistosome cercariae. Therefore, issuing early warnings on the risk of infection is an important preventive measure against schistosomiasis. Sentinel mice are used to monitor water body infestations, and identifying appropriate antibody responses to schistosome antigens for early detection of infection would help to improve the efficiency of this system. In this study we explored the potential of detecting antibodies to the hydrophilic domain (HD) of the 23-kDa membrane protein (Sj23HD) and soluble egg antigen (SEA) of <it>Schistosome japonicum </it>for early detection of schistosome infection in sentinel mice.</p> <p>Results</p> <p>Development of IgM and IgG antibody levels against Sj23HD and SEA in <it>S. japonicum </it>infected mice was evaluated over the course of 42 days post-infection by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The Sj23HD and SEA specific IgM and IgG levels in mice all increased gradually over the course of infection, but IgM and IgG antibodies against Sj23HD presented earlier than those against SEA. Furthermore, the rates of positive antibody responses against Sj23HD were higher than those against SEA in the early stage of schistosome infection, suggesting that the likelihood of detecting early infection using anti-Sj23HD responses would be higher than that with anti-SEA responses. The use of immunoblotting could further improve the early detection of schistosome infection due to its greater sensitivity and specificity compared to ELISA. Additionally, the levels of Sj23HD and SEA specific antibodies positively correlated with the load of cercariae challenge and the duration of schistosome infection.</p> <p>Conclusions</p> <p>This study demonstrated that antibody responses to the Sj23HD antigen could be monitored for early detection of schistosome infection in mice, especially by immunoblotting which demonstrated greater sensitivity and specificity than ELISA for detection Sj23HD antibodies.</p

Dual Anti-Inflammatory and Anti-Angiogenic Action of miR-15a in Diabetic Retinopathy

AbstractActivation of pro-inflammatory and pro-angiogenic pathways in the retina and the bone marrow contributes to pathogenesis of diabetic retinopathy. We identified miR-15a as key regulator of both pro-inflammatory and pro-angiogenic pathways through direct binding and inhibition of the central enzyme in the sphingolipid metabolism, ASM, and the pro-angiogenic growth factor, VEGF-A. miR-15a was downregulated in diabetic retina and bone marrow cells. Over-expression of miR-15a downregulated, and inhibition of miR-15a upregulated ASM and VEGF-A expression in retinal cells. In addition to retinal effects, migration and retinal vascular repair function was impaired in miR-15a inhibitor-treated circulating angiogenic cells (CAC). Diabetic mice overexpressing miR-15a under Tie-2 promoter had normalized retinal permeability compared to wild type littermates. Importantly, miR-15a overexpression led to modulation toward nondiabetic levels, rather than complete inhibition of ASM and VEGF-A providing therapeutic effect without detrimental consequences of ASM and VEGF-A deficiencies