Discovery of natural estrogen receptor modulators with structure-based virtual screening

Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ERα and ERβ. Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC₅₀ values ranging from several micromolar to 100 micromolar. In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC₅₀ value of 2.55 and 4.68 μM for ERα and ERβ, respectively. Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation.     

Neuroactive diol and acyloin metabolites from cone snail-associated bacteria

The bacterium Gordonia sp. 647 W.R.1a.05 was cultivated from the venom duct of the cone snail, Conus circumcisus. The Gordonia sp. organic extract modulated the action potential of mouse dorsal root ganglion neurons. Assay-guided fractionation led to the identification of the new compound circumcin A (1) and 11 known analogs (2–12). Two of these compounds, kurasoin B (7) and soraphinol A (8), were active in a human norepinephrine transporter assay with K_i values of 2575 and 867 nM, respectively. No neuroactivity had previously been reported for compounds in this structural class. Gordonia species have been reproducibly isolated from four different cone snail species, indicating a consistent association between these organisms.     

Psammaplysin F: A unique inhibitor of bacterial chromosomal partitioning

Described is the antibiotic activity of a marine natural product. Psammaplysin F (1) inhibited the growth of four Gram-positive strains by >80% at 50 μM, and the amine at position C-20 is responsible for the observed antibacterial activity. When tested against two strains of methicillin resistant Staphylococcus aureus (MRSA), the minimum inhibitory concentrations (MICs) for psammaplysin F (40–80 μM) were similar to the structurally-related alkaloid psammaplysin H (2). Psammaplysin F (1) increased membrane permeability by two to four-fold compared to psammaplysin H (2) or control-treated bacteria, respectively. Unlike psammaplysin H (2), we show that psammaplysin F (1) inhibits equal partitioning of DNA into each daughter cell, suggesting that this natural product is a unique prokaryotic cell division inhibitor.     

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.     

Synthesis and biological evaluation of prodigiosene conjugates of porphyrin,estrone and 4-hydroxytamoxifen

To generate the first series of prodigiosene conjugates, the tripyrrolic skeleton was appended to estrone, tamoxifen and porphyrin frameworks by way of ester linkers and various hydrocarbon chain lengths. The ability of the conjugates to inhibit various types of cancer cells was evaluated in vitro. The porphyrin conjugates did not exhibit significant activity. The estrone conjugates exhibited modest activity, for the most part. However, significantly greater growth inhibition activity against certain breast, colon, lung, leukemia, melanoma and prostate cell lines was noted. This unusual effect for this first generation model class of compound warrants further investigation and comparison to cases where estrogens are linked to prodigiosenes via connection points that do not feature in estrogen receptor binding. The 4-hydroxytamoxifen conjugates exhibit nanomolar range activity against the MCF-7 breast cancer cell line, paving the way to expand the scope and connectivity of prodigiosene–tamoxifen conjugates.     

广西弄岗国家级自然保护区植物物种多样性初步研究

对广西弄岗国家级自然保护区(以下简称弄岗保护区)维管植物物种多样性组成,包括对异名的订正、新发现类群和新发表类群的添加以及广西新记录种、特有种、国家或区级重点保护物种的统计等进行整理和研究。结果表明:弄岗保护区共计有维管植物1752种,隶属于184科810属。其中蕨类植物中国特有种39种、种子植物广西特有种101种、岩溶特有植物278种、珍稀濒危植物33种、广西重点保护野生植物73种、广西新记录种9种以及植物新类群17种。     

Resilience of a forest fragment exposed to long-term isolation in Singapore

Background: Fragmentation can fundamentally alter the structure of tropical forests. However, the impacts of fragmentation may vary significantly among regions and lead to different outcomes.

Aims: We examined the structure, composition and dynamics of a forest fragment in Singapore to investigate reasons for the apparent resilience of this forest to long-term isolation.

Methods: We conducted 5 censuses of 12,688 trees ≥1-cm dbh in a 2-ha plot on the edge of the fragment between 1993 and 2012.

Results: Stem density and basal area were not significantly different between 1993 and 2012 and were typical of other south-east Asian forests. However, there were short-term decreases in both variables after droughts in 1997 and 2009, both followed by recovery. Total mortality rate over the 19 years was 3.3% year^?1, considerably higher than other tropical forests in Asia, but it was balanced by high recruitment. The 10 most abundant species were primary forest species, pioneer species comprised <5% of all stems, and none of the 338 species in the plot was exotic. However, species abundances changed more than expected by chance for 86 species, and the rank order of the commonest species changed significantly. Species abundance changes were not related to known species traits.

Conclusions: Despite the long period of isolation, we found a surprising level of resilience of the Bukit Timah forest. While the forest may be more sensitive to the effects of climatic fluctuations at decadal time scales, there were very few signs of forest degradation in this diverse fragment of tropical forest.     

Simulated impact of the renewable fuels standard on US Conservation Reserve Program enrollment and conversion

A socioeconomic model is used to estimate the land‐use implications on the U.S. Conservation Reserve Program from potential increases in second‐generation biofuel production. A baseline scenario with no second‐generation biofuel production is compared to a scenario where the Renewable Fuels Standard (RFS2) volumes are met by 2022. We allow for the possibility of converting expiring CRP lands to alternative uses such as conventional crops, dedicated second‐generation biofuel crops, or harvesting existing CRP grasses for biomass. Results indicate that RFS2 volumes (RFS2‐v) can be met primarily with crop residues (78% of feedstock demand) and woody residues (19% of feedstock demand) compared with dedicated biomass (3% of feedstock demand), with only minimal conversion of cropland (0.27 million hectares, <1% of total cropland), pastureland (0.28 million hectares of pastureland, <1% of total pastureland), and CRP lands (0.29 million hectares of CRP lands, 3% of existing CRP lands) to biomass production. Meeting RFS2 volumes would reduce CRP re‐enrollment by 0.19 million hectares, or 4%, below the baseline scenario where RFS2 is not met. Yet under RFS2‐v scenario, expiring CRP lands are more likely to be converted to or maintain perennial cover, with 1.78 million hectares of CRP lands converting to hay production, and 0.29 million hectares being harvested for existing grasses. A small amount of CRP is harvested for existing biomass, but no conversion of CRP to dedicated biomass crops, such as switchgrass, are projected to occur. Although less land is enrolled in CRP under RFS2‐v scenario, total land in perennial cover increases by 0.15 million hectares, or 2%, under RFS2‐v. Sensitivity to yield, payment and residue retention assumptions are evaluated.     

北京雾灵山自然保护区冬春季地面活动鸟兽红外相机初步调查

为了解北京雾灵山自然保护区野生动物资源现状,于2014年11月至2015年4月,在保护区内放置30台红外相机开展调查。结果共记录鸟类5目14科27种,兽类4目8科10种,其中勺鸡(Pucrasia macrolopha)、红角鸮(Otus sunia)、纵纹腹小鸮(Athene noctua)和中华斑羚(Naemorhedus griseus)为国家Ⅱ级重点保护野生动物。鸟类物种数月变化剧烈。相对丰富度最高的6种动物为狍(Capreolus pygargus)(60.19)、红嘴蓝鹊(Urocissa erythrorhyncha)(34.14)、星鸦(Nucifraga caryocatactes)(27.78)、岩松鼠(Sciurotamias davidianus)(23.34)、松鸦(Garrulus glandarius)(23.34)、中华斑羚(21.99)。对狍、岩松鼠、中华斑羚进行日活动节律分析,狍属晨昏活动型;中华斑羚有两个活动高峰;岩松鼠的日活动高峰集中在晨间,为单峰型。本研究提供了北京雾灵山部分鸟兽资源的最新动态现状及活动节律信息,同时表明红外相机在拍摄地栖性鸟类、大中型兽类、夜行性动物方面具有优势,而对于非地栖鸟类和小型兽类,红外相机有一定局限性。本研究为应用红外相机技术开展森林野生动物多样性监测提供了经验。