Dynamic regulation of G-protein signaling in the phototransduction cascade ensures the high temporal resolution of vision. In a key step, the activated α-subunit of transducin (Gαt-GTP) activates the ...cGMP phosphodiesterase (PDE) by binding the inhibitory γ-subunit (PDEγ). Significant progress in understanding the interaction between Gαt and PDEγ was achieved by solving the crystal structure of the PDEγ C-terminal peptide bound to Gαt in the transition state for GTP hydrolysis (Slep, K. C., Kercher, M. A., He, W., Cowan, C. W., Wensel, T. G., and Sigler, P. B. (2001) Nature 409, 1071–1077). However, some of the structural elements of each molecule were absent in the crystal structure. We have probed the binding surface between the PDEγ C terminus and activated Gαt bound to guanosine 5′-O-(3-thio)-triphosphate (GTPγS) using a series of full-length PDEγ photoprobes generated by intein-mediated expressed protein ligation. For each of seven PDEγ photoprobe species, expressed protein ligation allowed one benzoyl-l-phenylalaine substitution at selected hydrophobic C-terminal positions, and the addition of a biotin affinity tag at the extreme C terminus. We have detected photocross-linking from several PDEγ C-terminal positions to the Gαt-GTPγS N terminus, particularly from PDEγ residue 73. The overall percentage of cross-linking to the Gαt-GTPγSN terminus was analyzed using a far Western method for examining Gαt-GTPγS proteolytic digestion patterns. Furthermore, mass spectrometric analysis of cross-links to Gαt from a benzoyl-phenylalanine replacement at PDEγ position 86 localized the region of photoinsertion to Gαt N-terminal residues Gαt-(22–26). This novel Gαt/PDEγ interaction suggests that the transducin N terminus plays an active role in signal transduction.
Objective
To evaluate the efficacy of Bufei Yishen Granule (补肺益肾颗粒, BFYSG) combined with Shufei Tie (舒肺贴) acupoint sticking therapy on quality of life of patients with stable chronic obstructive ...pulmonary disease (COPD).
Methods
A multi-center, double-blinded, double-dummy and randomized controlled method was adopted in this trial. A total of 244 patients were randomly assigned to a trial group and a control group according to the random number, each with 122 patients; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent form. In the trial group, patients were treated with BFYSG combined with “Shufei Tie” acupoint sticking therapy and sustained-release theophylline dummy, and in the control group patients were treated with oral sustained-release theophylline and BFYSG dummy combined with “Shufei Tie” acupoint sticking therapy dummy. The therapeutic course for two groups was 4 months and the follow-up was 6 months. The frequency and duration of acute exacerbation calculated by adding up each frequency and duration of acute exacerbation in treatment and follow-up time respectively, the quality of life measured by the World Health Organization Quality of Life (WHOQOL)-BREF scale and adult COPD quality of life (COPD-QOL) scale were observed.
Results
Among the 244 enrolled patients, 234 were screened for full analysis set (FAS); 221 were screened for per-protocol analysis set (PPS). After 4-month treatment and 6-month follow-up there were differences between the trial group and the control group in frequency of acute exacerbation (FAS:
P
=0.013; PPS:
P
=0.046); duration of acute exacerbation (FAS:
P
=0.005; PPS:
P
=0.006); scores of physiological, psychological and environment aspects of the WHOQOL-BREF questionnaire (FAS:
P
=0.002,
P
=0.006,
P
=0.000; PPS:
P
=0.00,
P
=0.001,
P
=0.000); scores of daily living ability, social activity, depression symptoms aspects of the COPD-QOL questionnaire (FAS:
P
=0.000,
P
=0.000,
P
=0.006; PPS:
P
=0.002,
P
=0.001,
P
=0.001).
Conclusion
BFYSG combined with acupoint sticking therapy could improve the quality of life of patients with stable COPD.
High-quality Cd
Zn
Se and Cd
Zn
Se/ZnS core/shell quantum dots (QDs) emitting in the violet-green spectral range have been successfully prepared using hydrothermal methods. The obtained aqueous Cd
Zn
...Se and Cd
Zn
Se/ZnS QDs exhibit a tunable photoluminescence (PL) emission (from 433.5 nm to 501.2 nm) and a favorable narrow photoluminescence bandwidth full width at half maximum (FWHM): 30-42 nm. After coating with a ZnS shell, the quantum yield increases from 40.2% to 48.1%. These Cd
Zn
Se and Cd
Zn
Se/ZnS QDs were characterized by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared (FTIR) spectroscopy. To further understand the alloying mechanism, the growth kinetics of Cd
Zn
Se were investigated through measuring the fluorescence spectra and X-ray diffraction spectra at different growth intervals. The results demonstrate that the inverted ZnSe/CdSe core/shell structure is formed initially after the injection of Cd
. With further heating, the core/shell structured ZnSe/CdSe is transformed into alloyed Cd
Zn
Se QDs with the diffusion of Cd
into ZnSe matrices. With increasing the reaction temperature from 100 °C to 180 °C, the duration time of the alloying process decreases from 210 min to 20 min. In addition, the cytotoxicity of Cd
Zn
Se and Cd
Zn
Se/ZnS QDs were investigated. The results indicate that the as-prepared Cd
Zn
Se/ZnS QDs have low cytotoxicity, which makes them a promising probe for cell imaging. Finally, the as-prepared Cd
Zn
Se/ZnS QDs were utilized to ultrasensitively and selectively detect Hg
ions with a low detection limit (1.8 nM).
To explore the influencing factors on physical endurance among Chinese primary and middle school students aged 10-17.
Data was used from "2010 National Physical Fitness and Health Surveillance", from ...which 68 458 primary and middle school students with complete information were selected. Good physical endurance was defined as endurance running time ≤ P 25 of same gender and age, poor physical endurance as ≥ P 75 of same gender and age. Difference of endurance running time in different physical endurance groups was compared; chi-square test, logistic regression and multiple level model were used to analyze influence of region, BMI, diet, exercise and exercise willingness on physical endurance.
There were 34 293 (50.0%) students of good physical endurance and 34 219 (50.0%) ones of poor physical endurance in 68 458 subjects. Percentage of good physical endurance was 53.8% (18 285/33 996) in rural students, higher than urban ones (46.3% (15 954/34 462)) (χ(2) = 384.16, P < 0.01). Percentage of good physical endu
Since 1965, polybrominated diphenyl ethers (PBDEs) have been used internationally as flame-retardant additives. PBDEs were recently withdrawn from commerce in North America and Europe due to their ...environmental persistence, bioaccumulative properties and endocrine-disrupting effects. Generations exposed perinatally to the highest environmental doses of PBDE account for one-fifth of the total United States population. While, toxicity of PBDE for the male reproductive system has been demonstrated in several human and animal studies, the long-lasting effects of perinatal exposures on male reproduction are still poorly understood. In this study, pregnant Wistar rats were exposed to 0.2mg/kg 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) from gestation day 8 until postnatal day 21. Male reproductive outcomes were analyzed on postnatal day 120 in offspring. Exposed animals had significantly smaller testes, displayed decreased sperm production per testis weight, had significantly increased percentage of morphologically abnormal spermatozoa, and showed an increase in spermatozoa head size. Perinatal BDE-47 exposure led to significant changes in testes transcriptome, including suppression of genes essential for spermatogenesis and activation of immune response genes. In particular, we observed a 4-fold average decrease in expression of protamine and transition protein genes in testes, suggesting that histone-protamine exchange may be dysregulated during spermatogenesis, resulting in an aberrant sperm epigenome. The possibility of long-lasting effects of developmental PBDE exposures calls for additional studies to build a foundation for the development of preventive and protective interventions against the environmentally-induced decline in fertility.
In order to obtain a novel absorbent with high adsorption capacity for the purification of immunoglobulin G (IgG), continuous supermacroporous agarose beads embedded agarose–chitosan composite ...monolithic cryogels (agarose–chitosan cryogels) were prepared by cryo-copolymerization of agarose–chitosan blend solutions with glutaraldehyde as the crosslinker in the presence of agarose beads. After coupling 2-mercaptopyridine onto divinylsulfone-activated matrix, the obtained cryogels were used for the purification of IgG. The microstructure morphologies of the cryogels were analyzed by scanning electron microscopy. The results showed that the obtained cryogels possess interconnected pores of 10–100μm size. The specific surface area was 350m2/g with maximum adsorption capacity of IgG 71.4mg/g. The cryogels showed workable stability, and can be reused at least 15 times without significant loss in adsorption capacity. IgG purity after one-step purification from human plasma was monitored by electrophoresis and the average recovery was estimated to be 90%.
To study the relationship between ovarian clear cell adenocarcinoma and DNA damage.
14 samples were selected from clinical ovarian cases including 3 cases with normal ovarian tissue, 6 cases with ...poorly differentiated ovarian tumor, 5 cases with ovarian clear cell adenocarcinoma, treated by X-ray irradiation and frozen sections respectively. DNA damage response was analyzed by immunofluorescence and Western blot.
Before X-ray irradiation, compared to normal ovarian tissue, a large number of endogenous damage existed in ovarian clear cell adenocarcinoma, and phosphorylation of histone family 2A variant (H2AX) was abnormally enhanced 1 hour after irradiation treatment, however, DNA repair was normal in ovarian clear cell adenocarcinoma. Phosphorylation of H2AX was dispensable for p53 binding protein 1 (53BP1) activation and couldn't be colocalized in clear-type ovarian cancer tissues.
The abnormal DNA damage activation implies that the network of DNA damage signaling pathway may be defective.
Guattegaumerine is a natural product with characteristics of being lipophilic and reaching high concentration in the brain, but its function in the central nervous system has not yet been observed. ...This study was designed to evaluate the neuroprotective effects of guattegaumerine on rat primary cultured cortical neurons. Following a 24-h exposure of the cells to combined serum-starvation and hydrogen peroxide, a significant augment in neuron damage as determined by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) release were observed. Preincubation of guattegaumerine dramatically improved the cell viability and inhibited LDH release. Preincubation of guattegaumerine also dramatically inhibited malondialhehyde (MDA) production and elevated the decreased total antioxidative capacity in cells caused by the combined injury. Results of flow cytometry and immunohistochemistry showed that pre-addition of guattegaumerine interrupted the apoptosis of the neurons, reversed the up regulation of the pro-apoptotic gene (Bax) and the down regulation of the anti-apoptotic gene (Bcl-2). Furthermore, guattegaumerine suppressed the increase of intracellular calcium (Ca²⁺i) stimulated by either H₂O₂ or KCl in Ca²⁺-containing extracellular solutions, and high concentration of 2.5 μM guattegaumerine also suppressed the increase of Ca²⁺i induced by H₂O₂ in Ca²⁺-free solution. These observations suggested that guattegaumerine may possess potential protection against oxidative stress injury, which might be beneficial for neurons.
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