In vitro structure–activity relationships of aplysinopsin analogs and their in vivo evaluation in the chick anxiety–depression model

Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms and have been shown to possess a range of biological activities. In vitro receptor binding assays showed that of the 12 serotonin receptor subtypes, analogues showed a high affinity for the 5-HT_2B and 5-HT_2C receptor subtypes, with selectivity for 5-HT_2B over 5-HT_2C. While no conclusions could be drawn about the number and position of N-methylations, bromination at C-4 and C-5 of the indole ring resulted in greater binding affinities, with K_i’s as low as 35 nM. This data, combined with previous knowledge of the CNS activity of aplysinopsin analogs, suggested that these compounds may have potential as leads for antidepressant drugs. Compounds 3c, 3u, and 3x were evaluated in the chick anxiety–depression model to assess their in vivo efficacy. Compound 3c showed a modest antidepressant effect at a dose of 30 nM/kg in the animal model.     

Assessing hydrologic alteration: Evaluation of different alternatives according to data availability

The natural flow regime of rivers across the world has been largely modified. Understanding the extent to which the flow regime deviates from natural conditions is necessary for designing sound management and restoration measures. In this regard, ‘Indicators of Hydrologic Alteration’ is currently considered one of the most effective approaches for assessing hydrologic alteration (HA). However, several generalized drawbacks such as the climatic variability between the pre- and post-impacted series and the scarcity of hydrological data in many impaired rivers should be addressed. In this study, a protocol with the following five alternative designs based on data availability is presented: (1) Paired-Before–After Control–Impact (BACIP), (2) Before–After (BA), (3) Control–Impact (CI), (4) Hydrological Classification (HC) and (5) Predicted Hydrological indices (HP). BACIP compares the status of the impacted gauge before and after the perturbation is started, in addition to controlling for natural climatic changes. Hence, it has been considered as the reference benchmark for all other designs. When this protocol was applied to 11 reservoirs situated in the northern third of the Iberian Peninsula, the BA design was able to correctly identify most of the non-significant HA but failed in almost one quarter of the significant alterations. Similarly, BACIP and CI showed an agreement of >80%. This suggests that the method is suitable when proper data are unavailable for BACIP or BA. In addition, our results indicated that the critical thresholds for HA varied depending on the hydrological index being considered. Significant HAs ranged from <5% for the number of days with increasing and decreasing flows to >64% for the duration of low-flow pulses. To delineate adequate thresholds, further research combining hydrological analyses with the biological response to the HA is warranted. Finally, the application of HC and HP designs revealed a significant degree of uncertainty related to the intra-class variability and the predictive error of the models. Therefore, 25% of the analysis could not be evaluated. However, in the evaluable cases, the HC and HP designs correctly assessed >75% of the HA, which highlighted the potential of this method in cases of scarce streamflow data.     

The cost-effectiveness of using raptor nest sites to identify areas with high species richness of other taxa

Given the limited resources available for conservation, it is important that the areas to preserve are selected in a cost effective manner. However, the cost effectiveness of the surrogate species strategy (the use of information on one or more species to identify areas of value for other species for which there is no, or more limited, available information) has seldom been evaluated.In this study, we investigate the opportunity cost of setting aside breeding sites of two forest raptor species (the surrogate species) by evaluating their individual and combined contribution to preserve diversity of polypores (wood-decaying fungi) and birds against the contributions of previously established nature reserves. We use numeric optimization models to compare different reserve selection strategies.Site selection based on nest sites of the dominant raptor species was more cost-effective than strategies using sites of the subordinate species or those processes previously used to select nature reserves in Finland. The inclusion of both raptor species in the reserve selection model further improved its performance relative to other approaches. This indicates that the means by which Finnish reserves are selected could be enhanced by including the breeding sites of these, and maybe other species, among the criteria used to select reserves in the future.These results show that information on charismatic and well-surveyed species could be a cost-efficient add-on to help enhance conservation endeavours. Where there is inter-specific competition for biodiverse sites, and using multiple species is costly, basing reserve selection primarily on breeding sites of a dominant species may be the best strategy. However, further work is required to establish the extent to which dominant species are typically better indicators of conservation relevance.     

Incorporating spatial autocorrelation in rarefaction methods: Implications for ecologists and conservation biologists

Recently, methods for constructing Spatially Explicit Rarefaction (SER) curves have been introduced in the scientific literature to describe the relation between the recorded species richness and sampling effort and taking into account for the spatial autocorrelation in the data. Despite these methodological advances, the use of SERs has not become routine and ecologists continue to use rarefaction methods that are not spatially explicit. Using two study cases from Italian vegetation surveys, we demonstrate that classic rarefaction methods that do not account for spatial structure can produce inaccurate results. Furthermore, our goal in this paper is to demonstrate how SERs can overcome the problem of spatial autocorrelation in the analysis of plant or animal communities. Our analyses demonstrate that using a spatially-explicit method for constructing rarefaction curves can substantially alter estimates of relative species richness. For both analyzed data sets, we found that the rank ordering of standardized species richness estimates was reversed between the two methods. We strongly advise the use of Spatially Explicit Rarefaction methods when analyzing biodiversity: the inclusion of spatial autocorrelation into rarefaction analyses can substantially alter conclusions and change the way we might prioritize or manage nature reserves.     

NK细胞中过表达Livin的实验研究

目的:将携带Livin的质粒pIRES2-EGFP-Livin进行扩增,转染自然杀伤细胞(NK)及胃癌细胞株SGC-7901,并检测其在NK及胃癌细胞株SGC-7901中的表达。方法:将携带Livin基因的质粒p IRES2-EGFP-Livin进行扩增,鉴定质粒纯度与浓度;从健康人外周血中获得NK细胞,应用HP转染试剂将质粒pIRES2-EGFP-Livin转染体外培养的NK及胃癌细胞,对比分析NK及胃癌细胞株SGC-7901中基因转染效率及目的基因的表达情况。结果:用无血清培养基在体外成功的扩增大量的NK细胞;质粒提取试剂盒抽提得到大量无内毒素的质粒,质粒DNA基因序列并未发生突变,浓度和纯度较高。胃癌细胞株SGC-7901中观察到明显的质粒pIRES2-EGFP-Livin绿色荧光表达;而NK中未观察到绿色荧光表达。结论:质粒pIRES2-EGFP-Livin能使Lvin蛋白表达于胃癌细胞株SGC-7901中,而在NK中未表达。     

Synthesis and Th1-immunostimulatory activity of α-galactosylceramide analogues bearing a halogen-containing or selenium-containing acyl chain

A novel series of CD1d ligand α-galactosylceramides (α-GalCers) were synthesized by incorporation of the heavy atoms Br and Se in the acyl chain backbone of α-galactosyl-N-cerotoylphytosphingosine. The synthetic analogues are potent CD1d ligands and stimulate mouse invariant natural killer T (iNKT) cells to selectively enhance Th1 cytokine production. These synthetic analogues would be efficient X-ray crystallographic probes to disclose precise atomic positions of alkyl carbons and lipid–protein interactions in KRN7000/CD1d complexes.     

Biodiversity analysis of natural arthropods enemies in vineyard agroecosystems in La Rioja,Spain

Major knowledge gaps exist regarding effects of landscape-level agroecosystem composition on the presence of natural enemies of agricultural pests. The objective of this study was to evaluate the influence of landscape mosaic characteristics on the diversity of predators and parasitoids of a viticultural landscape in La Rioja, Spain. Five habitats were evaluated: Mediterranean forest, Mediterranean scrub, olive groves, natural grassland, and vineyards. In all, we collected 28,640 arthropods, representing 10 orders: Araneae, Coleoptera, Dermaptera, Diptera, Hemiptera, Hymenoptera, Mantodea, Neuroptera, Solifugae, and Thysanoptera. The grassland habitat presented the highest arthropod abundances. Carabid beetles showed preferences for Mediterranean forest and scrub, whereas reduviid bugs showed preferences for natural grassland. Landscape heterogeneity and connectivity with natural elements in the study area turn out to be effective in conservation of diversity of natural enemies of viticulture.     

HSP60/10 chaperonin systems are inhibited by a variety of approved drugs,natural products,and known bioactive molecules

All living organisms contain a unique class of molecular chaperones called 60?kDa heat shock proteins (HSP60 – also known as GroEL in bacteria). While some organisms contain more than one HSP60 or GroEL isoform, at least one isoform has always proven to be essential. Because of this, we have been investigating targeting HSP60 and GroEL chaperonin systems as an antibiotic strategy. Our initial studies focused on applying this antibiotic strategy for treating African sleeping sickness (caused by Trypanosoma brucei parasites) and drug-resistant bacterial infections (in particular Methicillin-resistant Staphylococcus aureus – MRSA). Intriguingly, during our studies we found that three known antibiotics – suramin, closantel, and rafoxanide – were potent inhibitors of bacterial GroEL and human HSP60 chaperonin systems. These findings prompted us to explore what other approved drugs, natural products, and known bioactive molecules might also inhibit HSP60 and GroEL chaperonin systems. Initial high-throughput screening of 3680 approved drugs, natural products, and known bioactives identified 161 hit inhibitors of the Escherichia coli GroEL chaperonin system (4.3% hit rate). From a purchased subset of 60 hits, 29 compounds (48%) re-confirmed as selective GroEL inhibitors in our assays, all of which were nearly equipotent against human HSP60. These findings illuminate the notion that targeting chaperonin systems might be a more common occurrence than we previously appreciated. Future studies are needed to determine if the in vivo modes of action of these approved drugs, natural products, and known bioactive molecules are related to GroEL and HSP60 inhibition.     

Structural requirement of tunicamycin V for MraY inhibition

Elucidating a structure-activity relationship study by evaluating a series of truncated analogues is a simple but important and effective tactic in medicinal chemistry based on natural products with a large and complex chemical structure. In this study, a series of truncated analogues of tunicamycin V were designed and synthesized and their MraY inhibitory activity was investigated in order to gain insight into the effect of these moieties on MraY inhibition.