Design and synthesis of novel β-diketo derivatives as HIV-1 integrase inhibitors

A series of novel β-diketo derivatives which combined the virtues of 1,3-diketo, 1,2,3-triazole and polyhydroxylated aromatics moieties, were designed and synthesized as potential HIV-1 integrase (IN) inhibitors and evaluated their inhibition to the strand transfer process of HIV-1 integrase. The result indicates that 3,4,5-trihydroxylated aromatic derivatives exhibit good inhibition to HIV-1 integrase, but dihydroxylated aromatic derivatives and corresponding methoxy aromatic derivatives appear little inhibition to HIV-1 integrase.     

一株红树林真菌抗单纯疱疹病毒Ⅱ型的研究

目的:对分离自海南红树林真菌菌株PH0016的胞外多糖(exopolysaccharide,EPS)抗单纯疱疹病毒Ⅱ型(Herpes simplex virus type 2,HSV-2)活性进行研究。方法:收集纯化菌株PH0016产生的EPS,体外采用细胞病变观察EPS的细胞毒性和抗HSV-2作用。为观察EPS对HSV-2体内感染的治疗效果,小鼠颅内注射0.02ml滴度为100LD50/0.1ml-1的HSV-2,24小时后以不同浓度EPS灌胃,持续7天,14天后计算小鼠存活率和存活时间。菌株分类采用形态学观察和ITS序列分析。结果:EPS可抑制HSV-2病毒活性,病毒感染的细胞病变的半抑制浓度(Inhibited concentration,IC50)为313μg/mL,SI为11.43。EPS 25mg.kg-1.d-1灌胃后,小鼠存活率为40.0%,存活时间为9.82±1.87天,相比模型组实验动物存活时间和存活率均有提高。菌株初步鉴定为淡紫色拟青霉。结论:从海南红树林分离一株淡紫色拟青霉,其产生的EPS具有抗HSV-2活性,值得进一步研究。     

Volatiles from Merino fleece evoke antennal and behavioural responses in the Australian sheep blow fly Lucilia cuprina

To identify flystrike‐related volatile compounds in wool from Merino sheep, the attractiveness of wool to Lucilia cuprina Wiedmann (Diptera: Calliphoridae) was examined. First, a selection of wool samples guided by previous knowledge of sheep lines, predicted to be more susceptible or more resistant to flystrike, was tested. The attractiveness of the 10 samples selected was not associated with field susceptibility: two samples from the more resistant line were identified as most attractive and two samples from the more susceptible line were identified as least attractive, based on the behavioural assays with gravid flies. Comparison of the headspace volatiles of these samples, using solid phase microextraction and gas chromatography‐mass spectrometry‐electroantennographic detection, revealed octanal and nonanal to be present in the attractive wool samples that elicited responses from the fly antenna. Furthermore, the two compounds were not present in wool that was least attractive to L. cuprina. In laboratory bioassays, octanal and nonanal evoked antennal and behavioural responses in gravid L. cuprina, thus confirming their potential role as semiochemicals responsible for attracting L. cuprina to Merino sheep.     

Yaks and sheep trigger different changes in the grasshopper assemblages of the Qilian Mountains via differentially altering plant assemblages

1. The Qilian Mountains represent one of the key livestock‐raising grasslands in China. The two main herbivore species raised in this area – yaks and sheep – are of critical economical value. Grasshoppers compete with these animals for available nutrients, creating multifaceted relationships between livestock, grasshoppers and plants. A clear understanding of such relationships is lacking and is urgently needed to guide conservation efforts. 2. This study aims to document the effects of yak and sheep grazing on grasshopper assemblages and to elucidate the underlying mechanisms of such effects. 3. It is shown here that yaks and sheep impact grasshopper assemblages differently. Grasshopper assemblages exhibited lower density, biodiversity, richness, and evenness of distribution in yak‐grazed pastures than in grazing‐free grasslands. Sheep‐grazed pastures exhibited a dramatically divergent picture, with elevated density, biodiversity and richness, and a slightly decreased evenness of distribution. Grasshoppers were generally larger in grazed pastures than in grazing‐free grasslands, especially in yak‐grazed plots. 4. The present study suggests that differences between yak and sheep pastures in plant assemblage structure and plant traits are probably the underlying forces driving the differences in grasshopper assemblage structure and grasshopper traits, respectively. 5. The study shows that the grasshopper habitat indicator species differ between yak and sheep pastures, raising the possibility that such indicators can be used to monitor grassland usage and degradation in the Qilian Mountains. 6. These results provide novel insights into the dynamic interactions of common domesticated herbivore species, grasshoppers and plants in Qilian Mountains, which augment current knowledge and may ultimately lead to better conservation practices.     

The species richness pattern of vascular plants along a tropical elevational gradient and the test of elevational Rapoport's rule depend on different life‐forms and phytogeographic affinities

The research about species richness pattern and elevational Rapoport's rule (ERR) have been carried out mostly in the temperate regions in the recent years and scarcely in the tropical mountains; meanwhile, it is unclear whether the ERR is consistent among different life‐forms and phytogeographic affinities. Here, we compiled a database of plant species of Mount Kenya, a tropical mountain of East Africa, and divided these species into twelve groups depending on the life‐form and phytogeographic affinity of each species. We inspected the species richness pattern of each group along the elevation gradient and also tested ERR of each group using Stevens' method. Our results showed that species richness of the total species showed a positively skewed (hump‐shaped) pattern along the elevation gradient and different life‐forms and phytogeographic affinities showed similar hump‐shaped patterns as the total species. The average elevation range size of the total species and herbaceous species showed increasing patterns along the elevation gradient, while lycophytes and ferns, and woody species showed an obvious downward trend after peaking in the high elevation regions. We concluded that the widely distributed herbaceous species which also have broad elevation range sizes are more applicable to ERR, while the narrowly distributed woody species with small elevation range sizes occurring in the higher elevations could reverse ERR. Therefore, we concluded that the ERR is not consistent among different organisms in the same region.     

Ginseng stem‐leaf saponins in combination with selenium enhance immune responses to an attenuated pseudorabies virus vaccine

Pseudorabies, a herpesvirus infection, is mainly controlled by using attenuated live vaccines. In this study, the effect of ginseng stem and leaf saponins (GSLS) in combination with selenium (Se; in the form of sodium selenite) on vaccination against attenuated pseudorabies virus (aPrV) was evaluated. It was found that GSLS and Se have an adjuvant effect and that a combination of GSLS and Se stimulates significantly enhanced immune responses than does GSLS or Se alone. Following oral administration of GSLS, mice immunized with an attenuated PrV vaccine diluted in Se‐containing physiological saline solution (PSS) provoked a significantly stronger gB‐specific serum antibodies response (IgG, IgG1 and IgG2a), enhanced lymphocyte proliferation and cytolytic activity of NK cells, along with higher production of cytokines (IFN‐γ, IL‐12, IL‐5 and IL‐10) by splenocytes. Notably, the combination of GSLS and Se conferred a much higher resistance to fPrV challenge after immunization of the mice with aPrV vaccine. This study offers convincing experimental evidence that an injection of Se with oral GSLS is a promising adjuvant combination that improves the efficacy of vaccination against PrV and deserves further study regarding improvement of responses to other animal vaccines.     

Spectrum structures and biological functions of 8-mers in the human genome

The spectra of k-mer frequencies can reveal the structures and evolution of genome sequences. We confirmed that the trimodal spectrum of 8-mers in human genome sequences is distinguished only by CG2, CG1 and CG0 8-mer sets, containing 2,1 or 0 CpG, respectively. This phenomenon is called independent selection law. The three types of CG 8-mers were considered as different functional elements. We conjectured that (1) nucleosome binding motifs are mainly characterized by CG1 8-mers and (2) the core structural units of CpG island sequences are predominantly characterized by CG2 8-mers. To validate our conjectures, nucleosome occupied sequences and CGI sequences were extracted, then the sequence parameters were constructed through the information of the three CG 8-mer sets respectively. ROC analysis showed that CG1 8-mers are more preference in nucleosome occupied segments (AUC > 0.7) and CG2 8-mers are more preference in CGI sequences (AUC > 0.99). This validates our conjecture in principle.     

Peptidome analysis reveals the involvement of endogenous peptides in mouse pancreatic dysfunction with aging

Type 2 diabetes (T2D) is a glucose regulation disorder that has significantly enhanced mortality and the global disease burden. The prevalence of T2D has increased worldwide and is higher in the elderly. The function of pancreatic islets decreases with age, which is one important reason for the occurrence of diabetes in the elderly. Recently, peptidome analysis has attracted attention. However, the role of age-related peptides in pancreatic dysfunction has not been investigated extensively. Here, we conducted a comparison of endogenous peptides between pancreas from adult and aging mice by liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 2,089 peptides originating from 1,280 protein precursors were identified, of which 232 were upregulated and 183 were downregulated in the aging mice (fold change ≥ 2 and p < 0.05), suggesting that the expression of pancreatic peptides in mice varied with age. The molecular weight of most peptides was <3.0 kDa, and the isoelectric point distribution had a bimodal characteristic. Further analysis of cleavage site patterns indicated that proteases cleaved pancreatic proteins according to their rules. Moreover, Gene Ontology and pathway analyses showed that the differentially expressed peptides potentially had specific effects on pancreatic dysfunction. Some differential peptides were located within the domains of precursor proteins that were closely associated with the development of diabetes. We believe that our research may advance the current understanding of pancreas-derived peptides and that certain peptides may be involved in the etiology of diabetes.     

Intracellular expression of Vitreoscilla hemoglobin improves S-adenosylmethionine production in a recombinant Pichia pastoris

To develop an efficient way to produce S-adenosylmethionine (SAM), methionine adenosyltransferase gene (mat) from Streptomyces spectabilis and Vitreoscilla hemoglobin gene (vgb) were coexpressed intracellularly in Pichia pastoris, both under control of methanol-inducible promoter. Expression of mat in P. pastoris resulted in about 27 times higher specific activity of methionine adenosyltransferase (SMAT) and about 19 times higher SAM production relative to their respective control, suggesting that overexpression of mat could be used as an efficient method for constructing SAM-accumulating strain. Under induction concentration of 0.8 and 2.4% methanol, coexpression of vgb improved, though to different extent, cell growth, SAM production, and respiratory rate. However, the effects of VHb on SAM content (specific yield of SAM production) and SMAT seemed to be methanol concentration-dependent. When cells were induced with 0.8% methanol, no significant effects of VHb expression on SAM content and specific SMAT could be detected. When the cells were induced with 2.4% methanol, vgb expression increased SAM content significantly and depressed SMAT remarkably. We suggested that under our experimental scheme, the presence of VHb might improve ATP synthesis rate and thus improve cell growth and SAM production in the recombinant P. pastoris.