Design,synthesis and primary activity evaluation of l-arginine derivatives as amino-peptidase N/CD13 inhibitors

A series of l-arginine derivatives were designed, synthesized and assayed for their activities against amino-peptidase N (APN)/CD13 and metalloproteinase-2 (MMP-2). The results showed that most compounds exhibited high inhibitory activities against APN and low activities against MMP-2. Within this series, two compounds 5q and 5s (IC₅₀ = 5.3 and 5.1 μM) showed similar inhibitory activities compared with bestatin (IC₅₀ = 3.8 μM), which could be used as novel lead compounds for the future APN inhibitors development as anticancer agents.     

汶川地震后鸟兽资源现状: 以都江堰光光山峡谷区为例

<正>2008年"5.12"汶川特大地震及后续次生地质灾害(如崩塌、滑坡、泥石流和堰塞湖等)不仅给地震灾区人民造成了巨大生命和财产损失,也对该区域的野生动植物及其栖息地造成了长期的严重影响(欧阳志云等,2008)。地震发生地所属的岷山和邛崃山系是世界生物多样性保护的关键区域,区域内动植物资源十分丰富,是大熊猫(Ailuopoda melanolcuca)和川金丝猴(Rhinopithecus roxellanae)等珍稀野生动物的主要分布区(国家林业局,2006)。根据遥感影像数据,汶川地震及其所引起的各种次     

Light inhibition of the conversion of 1-aminocyclopropane-1-carboxylic acid to ethylene in leaves is mediated through carbon dioxide

The mechanism of light-inhibited ethylene production in excised rice (Oryza sativa L.) and tobacco (Nicotiana tabacum L.) leaves was examined. In segments of rice leaves light substantially inhibited the endogenous ethylene production, but when CO₂ was added into the incubation flask, the rate of endogenous ethylene production in the light increased markedly, to a level which was even higher than that produced in the dark. Carbon dioxide, however, had no appreciable effect of leaf segments incubated in the dark. The endogenous level of 1-aminocyclopropane-1-carboxylic acid (ACC), the immediate precursor of ethylene, was not significantly affected by lightdark or CO₂ treatment, indicating that dark treatment or CO₂exerted its effect by promoting the conversion of ACC to ethylene. This conclusion was supported by the observations that the rate of conversion of exogenously applied ACC to ethylene was similarly inhibited by light, and this inhibition was relieved in the presence of CO₂. Similar results were obtained with tobacco leaf discs. The concentrations of CO₂ giving half-maximal activity was about 0.06%, which was only slightly above the ambient level of 0.03%. The modulation of ACC conversion to ethylene by CO₂ or light in detached leaves of both rice and tobacco was rapid and fully reversible, indicating that CO₂ regulates the activity, but not the synthesis, of the enzyme converting ACC to ethylene. Our results indicate that light inhibition of ethylene production in detached leaves is mediated through the internal level of CO₂, which directly modulates the activity of the enzyme converting ACC to ethylene.Abbreviation ACC 1-aminocyclopropane-1-carboxylic acid Recipient of a Republic of China National Science Council Fellowship     

Correlation of zona-binding with oocyte maturation and sperm motility in rhesus monkeys by hemizona assay

The hemizona assay (HZA) in Rhesus monkeys was employed to study the correlation of zona-binding ability with sperm motility or with naturally developing oocytes at various maturational stages. Oocytes from unstimulated ovaries were retrieved within 2 hr from monkeys sacrificed for vaccine production (in reproductive season, but with their menstrual cycles not determined). Oocytes were divided into four groups based on their morphological maturation: 1) Oocytes surrounded by more than one cumulus layer (MC); 2) Oocytes retaining intact germinal vesicle nuclei (GV); 3) Oocytes with germinal vesicle breakdown showing distinct perivitelline space (PVS); and 4) Oocytes extruding the first polar body (PBI). The mean numbers of sperm bound to hemizona for PB1, PVS, GV, and MC groups were 132.9 ± 12.0, 71.5 ± 10.1, 36.1 ± 4.0, and 20.1 ± 2.9 (Mean ± SE), respectively. The four groups showed significant differences from each other in sperm/egg binding ability (P < 0.01). The number of bound sperm significantly increased with oocyte maturation. The present study also showed that zona-binding ability was also affected by sperm motility. For sperm with 67.7% motility and sperm with 31.2% motility, the average numbers of bound sperm were 43.5 ± 2.2 and 25.3 ± 2.9 (Mean ± SE), respectively. There was significantly higher binding ability for sperm with higher motility (P < 0.01). The results suggest that: 1) The rhesus monkey model can serve as a very sensitive model for studying sperm/egg interaction by HZA; 2) Sperm motility positively correlated with sperm/egg binding; and 3) Sperm/egg binding ability increases with oocyte maturation. The binding ability is highest when oocytes matured to the PB1 stage, which is also the best opportunity for fertilization. This is strong evidence for the “zona maturation” hypothesis. © 1994 Wiley-Liss, Inc.     

Phylogeography of the genus Dasiphora (Rosaceae) in the Qinghai‐Tibetan Plateau: divergence blurred by expansion

Plateau uprisings and climatic oscillations are considered to have caused extensive allopatric divergences that account for the rich species diversity of the Qinghai‐Tibetan Plateau (QTP). However, secondary contact during range shifts in the Quaternary glacial cycles or inter‐uplift stages may have restored the gene flow between species and so counteracted these divergences, particularly in rapidly‐adapting dominant elements. We tested this hypothesis by determining the phylogeographical history of Dasiphora (Rosaceae), a genus of two species that are widely distributed on the QTP and co‐exist in numerous localities. We sequenced two chloroplast DNA fragments (rbcL, trnT‐L) for 559 individuals from 87 populations. Bayesian methods were used to identify phylogenetic relationships and to estimate divergence times. Demographic histories were inferred using neutrality tests, mismatch distribution analysis, and coalescent simulation. A total of 112 haplotypes that clustered into three major groups were identified. The formation of these groups and their subgroups was dated to between the Pliocene and the late Pleistocene. In addition, we found that some groups underwent multiple extensive expansions. Species‐specific haplotypes were identified for each species, although these haplotypes phylogenetically intermixed. These results suggest that recent plateau uplifts and climatic oscillations might have caused the deep divergences observed within this genus. However, later range expansions probably blurred these divergences and possible species boundaries. Our results shed new light on the complex evolutionary history of the QTP alpine plants. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 111 , 777–788.     

MiR-320a down-regulation mediates bladder carcinoma invasion by targeting ITGB3

To investigate whether the miR-320a could regulate bladder cancer cells invasion by down-regulation of ITGB3. Real-time quantitative PCR was applied to evaluate the expression level of miRNA-320a in bladder transitional cell carcinomas (TCC) and normal bladder transitional cell (NBTC) samples. The invasion ability of miR-320a in TCC T24 cells was analyzed by Transwell assay after pre-miR-320a or anti-miR-125b transfection. For the invasion mechanism analysis of miR-320a on T24 cells, TargetScan, PicTar and miRBase were used to predict the possible target gene of miR-320a. Luciferase activities assay and western blot were used to reveal the predicted target gene of miR-320a were direct and specific. RNA interference technology was used to confirm the invasion inhibition of miR-320a was directly induced by ITGB3. Our study showed that miR-320a was down-regulated in human TCC specimens compared to that in NBTC specimens. Over-expression of miR-320a in T24 cells inhibited TCC invasion and this inhibitory effect on T24 cells could be restore by miR-320a knocked down. Mechanism analysis revealed that ITGB3 was a direct and specific target of miR-320a. The advanced effect of anti-miR-320a on TCC cell invasion was mediated by expression silence of ITGB3. In summary, aberrantly expressed miR-320a contribute to T24 cells invasion partly through directly down-regulating ITGB3 protein expression in TCC and this miRNA signature offers a novel potential therapeutic strategy for TCC.     

Prenatal diagnosis of pure partial monosomy 18p associated with holoprosencephaly and congenital heart defects

We applied CMA to detect chromosomal variations during a prenatal diagnosis and detected a 4.5 Mb pure microdeletion at 18p11.3 that was not detected by conventional karyotyping. Fluorescent in situ hybridization (FISH) analysis was performed to confirm the deletion. Accurate breakpoints of the deletion in this patient were used to build correlations between monosomy 18p and the concomitant phenotypes, particularly holoprosencephaly (HPE), which is rarely reported in monosomy 18p11.3.     

Oligomycins A and C,major secondary metabolites isolated from the newly isolated strain <Emphasis Type="Italic">Streptomyces diastaticus</Emphasis>

During the screening program for fungicides, one actinomycete strain ECO 00047 was isolated with the potential activity against fungus. According to the morphology and analysis of the nucleotide sequence of the 16S rRNA gene (1500 bp) this isolate was identified as Streptomyces diastaticus. The active compounds were separated by silica gel column chromatography, Sephadex LH-20 gel filtration and then purified by flash chromatography on C₁₈ (20–45 μm). The chemical structure of the bioactive compounds I and II were elucidated, based on the spectroscopic data of MS, IR, UV, ¹H-NMR, ¹³C-NMR and X-ray single crystal diffraction analysis. Compounds I and II were identical with oligomycins A and C, the macrolide antibiotics which have been known to be produced by Streptomyces diastatochromogenes, S. libani and S. avermitilis. The two compounds exhibited a strong activity against Aspergillus niger, Alternaria alternata, Botrytis cinerea and Phytophthora capsici but no activity toward bacteria. Although the two above antibiotics were known, their isolation has so far not been reported from S. diastaticus.