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961.
CQ Zhou YL Lin JX Chen LS Wang NN Yang W Zeng WH Chen 《Bioorganic & medicinal chemistry letters》2012,22(18):5853-5856
Inspired by the potent DNA-cleaving activity of the Cu(II) complex of monopyrrole-polyamide dimer 1 (i.e., 1@Cu(2+)), we designed a new dimeric dipyrrole-polyamide analog 2 with the aim to optimize the catalytic activities of the metal complexes of this type of polypyrrole-polyamides. Compound 2 was prepared in 50% yield from the reaction of 1-methyl-4-[(1-methyl-4-nitro-1H-pyrrole-2-carbonyl)-amino]-1H-pyrrole-2-carboxylic acid with 2,2'-(ethane-1,2-diylbis(oxy))diethanamine, and fully characterized on the basis of NMR ((1)H and (13)C), MS (ESI and HR) and IR. Spectrophotometric titration, ESI-MS and conductivity measurements indicated that compound 2 formed a 1:1 complex with Cu(2+) ion (i.e., 2@Cu(2+)). Agarose gel electrophoresis studies indicated that 2@Cu(2+) was capable of efficiently converting pBR322 DNA into open circular and linear forms under physiological conditions, most probably via an oxidative mechanism. Its overall catalytic activity was estimated to be at least 30-fold higher than that of 1@Cu(2+). The fact that the cleaving activities of these Cu(II) complexes parallel, exactly, their binding affinities, raises the possibility that the cleaving activities of polypyrrole-polyamide derivatives of the type can be regulated by the binding affinities. 相似文献
962.
963.
Background
All honey bee species (Apis spp) share the same sex determination mechanism using the complementary sex determination (csd) gene. Only individuals heterogeneous at the csd allele develop into females, and the homozygous develop into diploid males, which do not survive. The honeybees are therefore under selection pressure to generate new csd alleles. Previous studies have shown that the csd gene is under balancing selection. We hypothesize that due to the long separation from the mainland of Hainan Island, China, that the giant honey bees (Apis dorsata) should show a founder effect for the csd gene, with many different alleles clustered together, and these would be absent on the mainland.Methodology/Principal Findings
We sampled A. dorsata workers from both Hainan and Guangxi Provinces and then cloned and sequenced region 3 of the csd gene and constructed phylogenetic trees. We failed to find any clustering of the csd alleles according to their geographical origin, i.e. the Hainan and Guangxi samples did not form separate clades. Further analysis by including previously published csd sequences also failed to show any clade-forming in both the Philippines and Malaysia.Conclusions/Significance
Results from this study and those from previous studies did not support the expectations of a founder effect. We conclude that because of the extremely high mating frequency of A. dorsata queens, a founder effect does not apply in this species. 相似文献964.
965.
The Tibetan Plateau is an essential area to study the potential feedback effects of soils to climate change due to the rapid rise in its air temperature in the past several decades and the large amounts of soil organic carbon (SOC) stocks, particularly in the permafrost. Yet it is one of the most under-investigated regions in soil respiration (Rs) studies. Here, Rs rates were measured at 42 sites in alpine grasslands (including alpine steppes and meadows) along a transect across the Tibetan Plateau during the peak growing season of 2006 and 2007 in order to test whether: (1) belowground biomass (BGB) is most closely related to spatial variation in Rs due to high root biomass density, and (2) soil temperature significantly influences spatial pattern of Rs owing to metabolic limitation from the low temperature in cold, high-altitude ecosystems. The average daily mean Rs of the alpine grasslands at peak growing season was 3.92 μmol CO(2) m(-2) s(-1), ranging from 0.39 to 12.88 μmol CO(2) m(-2) s(-1), with average daily mean Rs of 2.01 and 5.49 μmol CO(2) m(-2) s(-1) for steppes and meadows, respectively. By regression tree analysis, BGB, aboveground biomass (AGB), SOC, soil moisture (SM), and vegetation type were selected out of 15 variables examined, as the factors influencing large-scale variation in Rs. With a structural equation modelling approach, we found only BGB and SM had direct effects on Rs, while other factors indirectly affecting Rs through BGB or SM. Most (80%) of the variation in Rs could be attributed to the difference in BGB among sites. BGB and SM together accounted for the majority (82%) of spatial patterns of Rs. Our results only support the first hypothesis, suggesting that models incorporating BGB and SM can improve Rs estimation at regional scale. 相似文献
966.
Bone marrow-derived mesenchymal stem cells (BMSCs) have shown great promise for ischemic tissue repair. However, poor viability of transplanted BMSCs within ischemic tissues has limited their therapeutic potential. Apelin, an endogenous peptide, whose level is elevated following ischemia, has been shown to enhance survival of cardiomyocytes and neuronal cells during ischemia. We hypothesized that apelin-13 protects BMSCs from apoptotic death. In this paper we determined the potential mechanism of apelin-13 effects using cultured BMSCs from adult rats. Apoptosis was induced by the specific apoptotic insult serum deprivation (SD) for up to 36 h. Apoptotic cell death was measured using immunostaining and Western blotting in the presence and absence of apelin-13 (0.1 to 5.0 nM) co-applied during SD exposure. SD-induced apoptosis was significantly reduced by apelin-13 in a concentration-dependent manner. SD-induced mitochondrial depolarization, cytochrome c release, and caspase-3 activation were largely prevented by apelin-13. The apelin-13 anti-apoptotic effects were blocked by inhibiting the MAPK/ERK1/2 and PI3K/Akt signaling pathways. Taken together, our findings indicate that apelin-13 is a survival factor for BMSCs and its anti-apoptotic property may prove to be of therapeutic significance in terms of exploiting BMSC-based transplantation therapy. 相似文献
967.
This article presents semiparametric joint models to analyze longitudinal data with recurrent events (e.g. multiple tumors, repeated hospital admissions) and a terminal event such as death. A broad class of transformation models for the cumulative intensity of the recurrent events and the cumulative hazard of the terminal event is considered, which includes the proportional hazards model and the proportional odds model as special cases. We propose to estimate all the parameters using the nonparametric maximum likelihood estimators (NPMLE). We provide the simple and efficient EM algorithms to implement the proposed inference procedure. Asymptotic properties of the estimators are shown to be asymptotically normal and semiparametrically efficient. Finally, we evaluate the performance of the method through extensive simulation studies and a real-data application. 相似文献
968.
Xia MF Yan HM He WY Li XM Li CL Yao XZ Li RK Zeng MS Gao X 《Obesity (Silver Spring, Md.)》2012,20(2):444-452
Accurate measures of liver fat content are essential for investigating the role of hepatic steatosis in the pathophysiology of multiple metabolic disorders. No traditional imaging methods can accurately quantify liver fat content. [(1)H]-magnetic resonance spectroscopy (MRS) is restricted in large-scale studies because of the practical and technological issues. Previous attempts on computer-aided ultrasound quantification of liver fat content varied in method, and the ultrasound quantitative parameters measured from different ultrasound machines were hardly comparable. We aimed to establish and validate a simple and propagable method for quantitative assessment of liver fat content based on the combination of standardized ultrasound quantitative parameters, using [(1)H]-MRS as gold standard. Totally 127 participants were examined with both ultrasonography (US) and [(1)H]-MRS. Ultrasound hepatic/renal echo-intensity ratio (H/R) and ultrasound hepatic echo-intensity attenuation rate (HA) were obtained from ordinary ultrasound images using computer program. Both parameters were standardized using a tissue-mimicking phantom before analysis. Standardized ultrasound H/R and HA were positively correlated with the liver fat content by [(1)H]-MRS (r = 0.884, P < 0.001 and r = 0.711, P < 0.001, respectively). Linear regression analysis showed ultrasound H/R could modestly predict the amount of liver fat (adjusted explained variance 78.0%, P < 0.001). The addition of ultrasound HA slightly improved the adjusted explained variance to 79.8%. Difference of estimated liver fat contents between different ultrasound machines and operators was reasonably well. Thus, computer-aided US is a valid method to estimate liver fat content and can be applied extensively after standardization of ultrasound quantitative parameters. 相似文献
969.
Chen ZY Zeng DY Hu YT He YW Pan N Ding JP Cao ZJ Liu ML Li WX Yi H Jiang L Wu YL 《PloS one》2012,7(4):e35154
Background
Although the basic scorpion K+ channel toxins (KTxs) are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K+ channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly.Principal Findings
Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses. Seven of these toxins belong to three new α-KTx subfamilies (α-KTx28, α-KTx29, and α-KTx30), and two are new members of the known κ-KTx2 subfamily. ImKTx104 containing three disulfide bridges, the first member of the α-KTx28 subfamily, has a low sequence homology with other known KTxs, and its NMR structure suggests ImKTx104 adopts a modified cystine-stabilized α-helix-loop-β-sheet (CS-α/β) fold motif that has no apparent α-helixs and β-sheets, but still stabilized by three disulfide bridges. These newly described acidic KTxs exhibit differential pharmacological effects on potassium channels. Acidic scorpion toxin ImKTx104 was the first peptide inhibitor found to affect KCNQ1 channel, which is insensitive to the basic KTxs and is strongly associated with human cardiac abnormalities. ImKTx104 selectively inhibited KCNQ1 channel with a Kd of 11.69 µM, but was less effective against the basic KTxs-sensitive potassium channels. In addition to the ImKTx104 toxin, HeTx204 peptide, containing a cystine-stabilized α-helix-loop-helix (CS-α/α) fold scaffold motif, blocked both Kv1.3 and KCNQ1 channels. StKTx23 toxin, with a cystine-stabilized α-helix-loop-β-sheet (CS-α/β) fold motif, could inhibit Kv1.3 channel, but not the KCNQ1 channel.Conclusions/Significance
These findings characterize the structural and functional diversity of acidic KTxs, and could accelerate the development and clinical use of acidic KTxs as pharmacological tools and potential drugs. 相似文献970.
Shing-Tai Pan Chih-En Kuo Jian-Hong Zeng Sheng-Fu Liang 《Biomedical engineering online》2012,11(1):1-19