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Although increasing evidence has documented the association of exposure to air pollution and childhood obesity, a limited number of studies have reported the relationship of air pollution exposure to early childhood body mass index (BMI) growth trajectories, which are strong predictors of future health. We aimed to examine the associations of prenatal and postnatal (first-year and second-year) exposure to nitrogen dioxide (NO2) and indicators of exposure to major roadways with obesity at 2 years old and BMI-for-age Z-score (BMIZ) growth trajectories between 0 and 2 years old. The length and weight of the children were repeatedly measured at birth and at 1 year (±1 month) and 2 years (±1 month) of age. Sex-specific BMIZs were calculated, and children with BMIZs greater than the 95th percentile were identified as cases of obesity (BMIZ cut-offs of childhood obesity were 1.78 for boys and 1.60 for girls). Exposure to NO2 was evaluated using a land use regression model. Two indicators for major roadways exposure (length of major roadways surrounding the residence and residential distance to the nearest major roadway) were calculated according to the residential address during pregnancy. We explored the prenatal NO2 exposure windows associated with incident obesity at 2 years old and found that the third trimester was the prenatal NO2 exposure window with the significant higher risk. Each 10 μg/m3 incremental change in prenatal exposure to NO2 was associated with a relative risk (RR) of 1.10 for childhood obesity (95% confidence interval: 1.01, 1.20). However, postnatal (first-year and second-year) exposure to NO2 was not associated with obesity risk at 2 years old. No significant associations were observed between indicators of exposure to major roadways and risk of obesity at 2 years old. In addition, prenatal exposure to the highest quartile of NO2 was significantly associated with a faster overall growth rate of the BMIZ from birth to the age of 2 years old (the slope of the BMIZ trajectories, β3 (standard error), for the 4th quartile vs. the 1st quartile: 0.88 (0.15), P value

Background Residential surrounding green spaces can affect human health. However, limited studies have examined their impacts on maternal blood glucose homeostasis outcomes. Objective We examined the associations of residential exposure to green space with maternal blood glucose levels, gestational impaired glucose tolerance (IGT), and gestational diabetes mellitus (GDM). Methods Pregnant women were recruited from a prospective birth cohort between October 2012 and September 2015. Exposure to green space was calculated as the mean value of the normalized difference vegetation index (NDVI) within a 300-m circular buffer area surrounding each residence. Maternal glucose was measured between 24 and 28 weeks of gestation, and gestational IGT and GDM were diagnosed using valid methods. We estimated the associations of residential NDVI with maternal glucose levels using multiple linear regression models with adjustment for age, education, BMI, passive smoking during pregnancy, parity, season of conception, income, and urbancity. We estimated the relative risks of residential NDVI with IGT and GDM using a generalized estimating equation model with modified Poisson regression. The mediation effects of residential exposure to air pollution and maternal physical activity were assessed using causal mediation analysis. Results Of 6807 pregnant women, 751 (11.3%) and 604 (8.8%) were diagnosed with IGT and GDM, respectively. One SD increment of residential NDVI was associated with a decrease of 0.06 mmol/L (95% CI: −0.07, −0.05), 0.09 mmol/L (95% CI: −0.13, −0.05), and 0.06 mmol/L (95% CI: −0.09, −0.03) in maternal fasting glucose levels, 1-h glucose levels, and 2-h glucose levels, respectively, as well as reduced risks of incident IGT (RR: 0.92, 95% CI: 0.86, 0.99) and GDM (RR: 0.85, 95% CI: 0.79, 0.92). The association between residential NDVI and maternal fasting glucose levels was partly mediated by maternal exposure to PM2.5. Conclusion Living with higher levels of green space was significantly associated with decreased maternal glucose levels and attenuated risks of incident maternal IGT and GDM. Our findings provide evidence linking green space to better maternal glucose outcomes. More studies are needed to further explore the maternal and child health benefits related to our findings.

Carbonaceous aerosol is one of the main ingredients of the atmospheric aerosol, which includes black carbon and organic carbon. The numerical simulations from 1960 to 2000 are aimed at the direct radiative effects on climate induced by carbonaceous aerosol in East Asia using NCAR Community Atmospheric Model version 3.1 (CAM). The mean radiative forcing(RF) under all sky in Chinese mainland at TOA and surface are 0.38 and −5.31W/m2 respectively. This distinct RF leads to −0.1K surface temperature decrease in Chinese mainland, which includes −0.26K drop of daily maximum and 0.07K rise of minimum temperature. Air column temperature has also been increased 0.11K in Chinese mainland. Significant vapor and precipitation increase can be resulted from RF of carbonaceous aerosol in north China and the Yellow and Huai River basin, accompanied by the decrease in northeast China, far-east region, and Tibet Plateau.

Like many other receptor tyrosine kinases (RTKs), platelet-derived growth factor (PDGF) receptor beta (PDGFR-beta) is internalized and degraded in lysosomes in response to PDGF stimulation, which regulates many aspects of cell signalling. However, little is known about the regulation of PDGFR-beta endocytosis. Given that ligand binding is essential for the rapid internalization of RTKs, the events induced by the ligand binding likely contribute to the regulation of ligand-induced RTK internalization. These events include receptor dimerization, activation of intrinsic tyrosine kinase activity and autophosphorylation. In this communication, we examined the role of PDGFR-beta kinase activity, PDGFR-beta dimerization and PDGFR-beta C-terminal motifs in PDGF-induced PDGFR-beta internalization. We showed that inhibition of PDGFR-beta kinase activity by chemical inhibitor or mutation did not block PDGF-induced PDGFR-beta endocytosis, suggesting that the kinase activity is not essential. We further showed that dimerization of PDGFR-beta is essential and sufficient to drive PDGFR-beta internalization independent of PDGFR-beta kinase activation. Moreover, we showed that the previously reported 14 amino acid sequence 952-965 is required for PDGF-induced PDGFR-beta internalization. Most importantly, we showed that this PDGFR-beta internalization motif is exchangeable with the EGFR internalization motif (1005-1017) in mediating ligand-induced internalization of both PDGFR-beta and EGFR. This indicates a common mechanism for the internalization of both PDGFR-beta and EGFR.

The cytotoxicity of Taxol represents both inhibition of cell proliferation and cell death. The drug blocked cells in the G2/M phase of the cell cycle. It has also been reported that Taxol induced cell apoptosis; however, the mode of action of Taxol is far from clear. In this communication, the cytotoxicity of Taxol in various breast cancer cell lines was carefully examined. We showed that Taxol treatment induced a biphasic decrease of viable cells. While the first phase of decrease occurred over concentrations ranging from 0.005 to 0.05 microM and the second phase of decrease occurred at concentrations ranging from 5 to 50 microM, there was a plateau between these ranges. We determined that the biphasic response was due to two different mechanisms. In the lower concentration range (0.005-0.05 microM), Taxol stabilized the spindle during mitosis, thereby blocking mitosis. This mitotic block led to the inhibition of cell proliferation and the induction of apoptosis. In the higher concentration range (5-50 microM), Taxol mainly increased the polymerization of microtubule and stimulated the formation of microtubule bundles, which blocked entry into S phase. This inhibition of S phase entry led to the inhibition of cell proliferation and the induction of necrosis. These findings may have profound clinical implications.

In the oviduct of Locusta migratoria, an inhibitory neuropeptide, PDVDHVFLRFamide (SchistoFLRFamide) has separate binding and activation regions. VFLRFamide is the minimum sequence required for binding, which is comparable to the parent peptide, whereas the His residue, which does not contribute to binding, is a critical amino acid for the inhibitory activity of the receptor. In this study, the His residue of HVFLRFamide was substituted by Tyr, Leu, Ile, or Val to yield a group of HVFLRFamide analogues. As revealed by bioassay, all of these hexapeptide analogues exert stimulatory effects on oviduct muscle contraction. However, results from three sets of binding experiments indicate that these stimulatory FMRFamide-related peptides (FaRPs) share the same binding site as PDVDHVFLRFamide and HVFLRFamide, the inhibitory FaRPs. First, unlabeled stimulatory FaRPs competitively displace bound [125I]YDVDHVFLRFamide. Second, two binding sites for the stimulatory peptide YVFLRFamide were identified and both of them have similar binding affinities and maximum binding capacities as the two binding sites for PDVDHVFLRFamide. Third, unlabeled PDVDHVFLRFamide and HVFLRFamide competitively displace the bound [125I]YVFLRFamide in the same manner as unlabeled YVFLRFamide. These findings suggest the presence of a novel ligand-receptor reaction system. In this system, inhibitory peptides and stimulatory peptides share a single receptor by having the same binding sequence VFLRFamide, but are able to produce opposite muscle responses due to differences in activation sites. Correspondingly, this single receptor could be coupled with two different intracellular signaling systems to mediate either inhibitory or stimulatory responses.

Fatty acid binding protein (FABP) is a major cytosolic protein in the flight muscle of the adult desert locust, Schistocerca gregaria. While it is normally expressed at high rates only at the beginning of the adult stage, a marked increase in FABP mRNA accumulation can be induced by flight. Extended flight leads to a 10-fold increase of FABP mRNA within 12 h. Injection of adipokinetic hormone which mobilizes lipid delivery also stimulates FABP transcription in a dose-dependent manner. FABP mRNA reaches its maximum 16 h after treatment and returns to its base level within 48 h. Purified low density lipophorin, when injected into resting locusts, causes a similar increase as adipokinetic hormone or flight, suggesting that the additional supply of fatty acids is the ultimate cause of the observed induction of FABP expression.

The flight muscle of mature adult desert locusts contains large amounts of a fatty acid binding protein (FABP). The protein, which is absent at the beginning of the adult stage, accumulates in muscle cytosol during the first 2 weeks after metamorphosis. In insects treated with metamorphosis controlling hormones and anti-hormones, the intracellular concentration of FABP was determined with enzyme-linked immunosorbent assays and electron microscopical/immunogold labeling techniques. FABP content was found to be similar in both sexes of normal adults and in precocious adults. No FABP, however, was found in last instar nymphs, methoprene induced supernumerary nymphs and azadirachtin induced over-aged nymphs. The results indicate that FABP synthesis does not occur prior to metamorphosis, but is always initiated in differentiated adult flight muscle. FABP synthesis in adult muscle, however, is not dierectly stimulated by any hormone from the brain or adjacent endocrine glands.

Hormonal control of flight muscle development was studied in the desert locust, Schistocerca gregaria through quantitative analysis of electron micrographs from normal adults, precocious adults (obtained after ethoxy-precocene treatment), as well as supernumerary nymphs (obtained by methoprene treatment) and azadirachtin-induced overaged nymphs. During the first 2 weeks after imaginal ecdysis, flight muscle of normal adults as well as its constituent mitochondria and myofibrils increased in size. The mitochondrial portion of the tissue enlarged from 17 to 30%. Similar growth of all components was observed in precocious adults, obtained after treatment of 3rd-instar nymphs with ethoxy-precocene. Overaged nymphs as well as 6th-instar, supernumerary nymphs did not exhibit growth of myofibrillar components; size and distribution of mitochondria however was similar to adult insects. The results indicate that metamorphosis is required for complete muscle differentiation and development. Mitochondrial growth, however, is largely independent of endocrine influences. The results are discussed in light of published biochemical findings.