天然产物中透明质酸酶抑制剂的研究

透明质酸酶抑制剂是对透明质酸酶的激活有抑制作用的物质。透明质酸酶是透明质酸的特异性裂解酶,而透明质酸在人体许多发育和调控过程中起重要作用,抑制透明质酸酶的活性可使透明质酸不被分解,维持正常的生理功能,笔者对天然产物中透明质酸酶抑制的研究开发进行了概述,并探讨了透明质酸酶抑制在医药及保健食品工业中的应用潜力。     

On the lack of specificity of proteins and its consequences for a theory of biological organization

It is now widely recognized that gene expression and cellular processes include a probabilistic component. However, this does not essentially modify the theory of genetic programming. This stochastic aspect, which is called noise, is usually conceived as a margin of fluctuation in the way the genetic program functions and the latter remains understood as a specific mechanism guided by genetic information. In contrast, recent data show that proteins do not possess a high level of specificity. They can interact with numerous molecular partners. As a consequence molecular interactions are not simply “noisy”. Because they are subject to large combinatorial interaction possibilities, they are also intrinsically stochastic and must be sorted out by the cell structure. This contradicts the genetic programming theory which is based on the idea that protein interactions are directed by their stereospecificity and genetic information. Taking into account the lack of protein specificity leads to a new theory. Natural selection acts not only in evolution but also in ontogenesis by sorting stochastic molecular interactions. In this frame, the making up of an organism, instead of being a simple bottom-top process in which information flows from genes to phenotypes, is both a bottom-top and top-bottom process. Genes provide proteins, but their stochastic interactions are sorted by selective constraints arising from the cell and multi-cellular structures, which are themselves subject to the action of natural selection.     

Determinants of growing season soil CO2flux in a Minnesota grassland

Soil CO₂ flux was measured across 947 plots at 7 experimentalgrassland sites at the Cedar Creek Natural History Area in order to determinethe relationships between soil CO₂ flux and environmental factors,living plant biomass, and soil C and N. Soil CO₂ flux increased asthe day progressed, and was positively related to aboveground biomass,belowground biomass, and soil % C. However, most of the variation in soilCO₂ flux explained by a multiple regression model(r ² = 0.55) was attributed to the different experimental sites (61%).Soil CO₂ flux increased with increasing aboveground plant biomass(explaining 16% of the model variation),belowground plant biomass (12%), and soil C and C:N ratio(6%). The length of time between aboveground biomass in aplot was clipped and soil CO₂ flux variedamong plots. Soil CO₂ flux declined with increased timesince clipping, supporting the idea that recently fixedcarbon is a significant component of soil CO₂ flux.Soil CO₂ flux did not follow standard Q₁₀relationships. Over a 20 °C temperature range,soil CO₂ flux tended to be lower in warmer plots.More work is necessary to understand what factors explainthe large differences that were seen among experimentalsites in soil CO₂ flux that could not be explainedby biomass or soil properties.     

Viridiflorol induces anti-neoplastic effects on breast,lung, and brain cancer cells through apoptosis

All active natural molecules are not fully exploited as therapeutic agents, causing delays in the advancement of anticancer drug discovery. Viridiflorol is a natural volatile element that may work as anti-cancer compound. We tested the anticancer properties of viridiflorol at different concentrations ranging from 0.03 to 300 μM in vitro on three cancer cells including breast (MCF-7), lung (A549) and brain (Daoy). The cancer cells responses were documented after treatment using MTT and Annexin V assays. Viridiflorol showed cytotoxic effects against all tested cell lines, reducing cell viability in a concentration-dependent manner with variable IC₅₀ values. Daoy and A549 cell lines were more sensitive to viridiflorol when compared with temozolomide and doxorubicin, respectively. Viridiflorol demonstrated the highest anticancer activity against the Daoy cells with an estimated IC₅₀ of 0.1 µM followed by MCF-7 at 10 µM, and A549 at 30 µM. In addition, upon exposure to concentrations ranging from 30 µM to 300 µM of viridiflorol, early and late apoptotic cell death was induced in a concentration dependent manner in Daoy (55.8%-72.1%), MCF-7 (36.2%-72.7%) and A459 (35%-98.9%) cell lines, respectively. In conclusion, viridiflorol demonstrates cytotoxic and apoptotic ability in three different cancer cell lines (brain, breast and lung).     

Efficient isotopic tryptophan labeling of membrane proteins by an indole controlled process conduct

A protocol for the efficient isotopic labeling of large G protein‐coupled receptors with tryptophan in Escherichia coli as expression host was developed that sufficiently suppressed the naturally occurring L‐tryptophan indole lyase, which cleaves tryptophan into indole, pyruvate, and ammonia resulting in scrambling of the isotopic label in the protein. Indole produced by the tryptophanase is naturally used as messenger for cell–cell communication. Detailed analysis of different process conducts led to the optimal expression strategy, which mimicked cell–cell communication by the addition of indole during expression. Discrete concentrations of indole and ¹⁵N₂‐L‐tryptophan at dedicated time points in the fermentation drastically increased the isotopic labeling efficiency. Isotope scrambling was only observed in glutamine, asparagine, and arginine side chains but not in the backbone. This strategy allows producing specifically tryptophan labeled membrane proteins at high concentrations avoiding the disadvantages of the often low yields of auxotrophic E. coli strains. In the fermentation process carried out according to this protocol, we produced ～15 mg of tryptophan labeled neuropeptide Y receptor type 2 per liter medium. Biotechnol. Bioeng. 2013; 110: 1681–1690. © 2013 Wiley Periodicals, Inc.     

Biology Teaching in Secondary Schools in France

The educational design of a project option in an Open University course on evolution, based on the use of a computer simulation of natural selection, is discussed and the simulation itself described.     

Using stable isotopes to investigate the dietary trophic level of fledgling songbirds

ABSTRACT Use of early successional habitat by mature forest birds during the postfledging period is well documented, but reasons for this habitat shift remain elusive. Although forest‐breeding songbirds are primarily insectivorous during the nestling and early fledgling periods due to high protein requirements, older fledglings may adopt a heavily frugivorous diet. Our objectives were to use stable isotopes to examine the dietary trophic level of juveniles of three species of mature forest songbirds to determine if juvenile songbirds heavily consume fruit resources during the postfledging period and to evaluate a possible link between diet and energetic condition. We collected the outer right rectrix and several body feathers from 34 Wood Thrushes (Hylocichla mustelina), 34 Ovenbirds (Seiurus aurocapilla), and 35 Scarlet Tanagers (Piranga olivacea) captured in regenerating clearcuts in southeastern Ohio in 2005 and 2006. We also collected fruit and arthropod samples from each clearcut. Isotopic values of body feathers were significantly higher (more enriched) than those of rectrices in all cases except values of δ¹³C for Ovenbirds where we found no difference between body and rectrix feathers. These results suggest that juvenile songbirds did not undergo a strong shift to frugivory during the postfledging period, and arthropods were the primary source of protein during the period when rectrix and body feathers were growing. In addition, the energetic condition of birds was not related to the isotopic signature of feathers. Although our results are inconsistent with the hypothesis that juveniles move into regenerating clearcuts enabling them to shift to a primarily frugivorous diet during the postfledging period, they may consume fruit for nonprotein requirements, such as lipids and carbohydrates.     

Minority of mammalian orthologs can be regarded as physiologically closest genes

Orthologs are genes from different genomes that originate from a common ancestor gene by speciation event. They are most similar by the structure of encoded proteins and therefore should have a similar function. Here I apply the principle used for detection of structural orthology for a genome-wide analysis of gene expression. For this purpose, I determine the mutual similarity rank in all-by-all comparison of among-tissues expression patterns. The expression of most part of human–mouse orthologs in homologous tissues is poorly correlated (average mutual coexpression rank is only 4835 out of 18,092). Genes from evolutionarily labile gene families, which experience rapid turnover of family composition, are among those with the strongest expression change. However, the revealed phenomenon is not limited to them. There is no or very weak relationship between protein sequence divergence and mutual coexpression rank. Also, generally there is no relationship between the ratio of nonsynonymous to synonymous nucleotide substitutions and coexpression rank. This relationship is tangible only within evolutionarily labile gene families. These results indicate that despite of a similar biochemical function of orthologs reflected in the conserved protein sequence, the physiological (systemic) context of this function can be changed. Also, these results suggest that gene biochemical function and its physiological role in the organism can evolve independently.     

First total synthesis of prasinic acid and its anticancer activity

The first total synthesis of prasinic acid is being reported along with its biological evaluation. The ten step synthesis involved readily available and cheap starting materials and can easily be transposed to large scale manufacturing. The crucial steps of the synthesis included the formation of two different aromatic units (7 and 9) and their coupling reaction. The synthetic prasinic acid exhibited moderate antitumor activity (IC₅₀ 4.3–9.1 μM) in different lines of cancer cells.     

Comparative toxicity,growth inhibitory and biochemical effects of terpenes and phenylpropenes on Spodoptera littoralis (Boisd.)

Eleven monoterpenes, phenylpropenes and sesquiterpenes were evaluated for their insecticidal and growth inhibitory activities against the second and fourth larval instars of Spodoptera littoralis. Among the tested compounds, 1,8-cineole revealed the highest fumigant toxicity against the 2nd and 4th larval instars with LC₅₀ values of 2.32 and 3.13 mg/L air, respectively. The monoterpenes, p-cymene, α-terpinene, (−)α-pinene and (−)-carvone were highly toxic to both larval stages as their LC₅₀ values ranged between 7.35 and 13.79 mg/L air against 2nd larval instar and between 14.66 and 32.02 mg/L air against 4th larval instar. In topical application assay against the 4th larval instar, (−)-carvone (LD₅₀ = 0.15 mg/larva) and cuminaldehyde (LD₅₀ = 0.27 mg/larva) were the most potent contact toxicants. In residual film assay, trans-cinnamaldehyde, (−)-citronellal and p-cymene showed the highest insecticidal activity against the 2nd larval instar, while α-terpinene and (−)-carvone were most effective compounds against the 4th larval instar. Moreover, the tested compounds caused strong growth reduction of both larval stages with growth inhibition higher than 80% in the 2nd larval instar and higher than 70% in the 4th larval instar. On the other hand, (−)-carvone, cuminaldehyde and (Z,E)-nerolidol showed pronounced inhibitory effects on acetylcholinesterase (AChE) and adenosine triphosphatases (ATPases) activity of S. littoralis larvae. Cuminaldehyde (IC₅₀ = 1.04 mM) and (Z,E)-nerolidol (IC₅₀ = 0.02 mM) caused the highest inhibition of AChE and ATPases, respectively. Taken together, the results indicate that monoterpenes, phenylpropenes and phenylpropenes could be used to develop new botanical insecticides for S. littoralis management.