Diterpenoids from Ajuga chamaepitys: Two neo-clerodane derivatives

From the whole plant of Ajuga chamaepitys two new neo-clerodane diterpenoids, ajugapitin and its dihydro derivative, have been isolated. Their     

Synthesis and relative stereochemistry of the four mercapturic acids derived from styrene oxide and N-acetylcysteine

The chemical reaction between (±)-styrene oxide and N-acetylcysteine produces both positional isomers ($\text{1}$ and $\text{2}$) as a mixture of diastereoisomers with a preference for the benzylic thioether isomer $\text{1}$ (2 : 1). Synthesis of the mercapturic acid conjugates from either (+)- or (?)-styrene oxide produces only two of the four possible stereoisomers. The single diastereoisomers of $\text{1}$ and $\text{2}$ were separated by high pressure liquid chromatography (HPLC) and identified by ¹H- and ¹³C-nuclear magnetic resonance (NMR). The relative stereochemistry at the benzylic carbon center of the mercapturic acid conjugates was assigned on the basis of the established chemical correlation between optically pure styrene oxide and its precursor mandelic acid, and considerations on the mechanism of ring opening of epoxides by sulfur nucleophiles. The stereochemical definition of the isomers $\text{3}$–$\text{6}$ should prove useful in investigations of the biotransformation of the glutathione (GSH) conjugates of styrene oxide.     

High mutagenicity and toxicity of a diol epoxide derived from benzo[a]pyrene

(±)-7β,8α-Dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BP 7,8-diol-9,10-epoxide) is a suspected metabolite of benzo[a]pyrene that is highly mutagenic and toxic in several strains of $\text{Salmonella}\text{typhimurium}$ and in cultured Chinese hamster V79 cells. BP 7,8-diol-9,10-epoxide was approximately 5, 10 and 40 times more mutagenic than benzo[a]pyrene 4,5-oxide (BP 4,5-oxide) in strains TA 98 and TA 100 of $\text{S.}\text{typhimurium}$ and in V79 cells, respectively. Both compounds were equally mutagenic to strain TA 1538 and non-mutagenic to strain TA 1535 of $\text{S.}\text{typhimurium}$. The diol epoxide was toxic to the four bacterial strains at 0.5–2.0 nmole/plate, whereas BP 4,5-oxide was nontoxic at these concentrations. In V79 cells, the diol epoxide was about 60-fold more cytotoxic than BP 4,5-oxide.     

Preparation of right-side-out plasma membrane vesicles from Penicillium cyclopium: a critical assessment of markers.

A plasma membrane fraction was obtained by the combined use of differential centrifugation and aqueous polymer two-phase partitioning techniques. Vanadate-inhibited ATPase and glucan synthase activities were highly enriched in this fraction, although the presence of ATPase activity which was not inhibited by vanadate, nitrate, molybdate, anyimycin A or azide was also detected. Other intracellular membrane marker activities were present at very low or undetectable levels. A further separation step using Percoll density gradient centrifugation resulted in the separation of a fraction which exclusively contained vanadate-inhibited ATPase activity, and was enriched with silicotungstic-acid-staining membrane material. Latency tests performed on the plasma membrane markers showed that the membrane vesicles were in the right-side-out orientation.     

Recurrences and Human Agential Meaning Grounding: Laying a Path in Walking

This article addresses the semiotic problem of how meaning is agentially grounded: how actual meaning is possible and is justifiably supported by agents’ capabilities and purposes. This article is particularly focused on human agential grounding; however, to a great degree, insights presented here can be extended to other living beings. Specifically, agential meaning is examined here inside the framework of agentive semiotics and embodied, situated and enactive cognition theories, in line with the mind-life continuity general thesis (which intends to naturalize mind and experience). To offer clarity and methodological precision about agential grounding, three explanation categories (called recurrences) are proposed: phylogenetic recurrence, the evolutionary basis for corporal/embodied grounding; ontogenetic recurrence, the developmental basis for individual meaning grounding; and collective recurrence, the basis for meaning recognized, attributed and assigned inside social contexts. These recurrences are conceived as three types of general processes that constantly enclose possibilities for purpose and meaning emergence in humans. As a result of these types of recurrences, two categories of human agendas or purposes are also proposed: individual and collective. Finally, remarks about how these categories can be useful for semiotic analysis and further research are suggested.     

A Lead ANRIL Polymorphism Is Associated with Elevated CRP Levels in Periodontitis: A Pilot Case-Control Study

Elevated high sensitive C-reactive protein (hsCRP) is a marker for systemic inflammation and a risk marker for atherosclerotic cardiovascular disease (ACVD), and has also been associated with periodontitis. Inter-individual variation for hsCRP in periodontitis has been shown. ANRIL is the strongest genetic susceptibility locus for both periodontitis and ACVD, and it is speculated that genetic variation in ANRIL may modulate inflammatory processes. Therefore, we explored the possible association between hsCRP plasma levels and a leading ANRIL single nucleotide polymorphism (SNP) in periodontitis patients and controls. 171 healthy subjects with North European descent (115 periodontitis and 56 controls) were included in this case-control study. hsCRP levels were determined and subjects were genotyped for the leading ANRIL SNP rs1333048. In a multivariate analysis, periodontitis, female gender, increasing BMI and homozygosity for the major allele (AA-genotype) of rs1333048 were significantly associated with elevated hsCRP plasma levels (p = 0.012, p = 0.004, p = 0.007 and p = 0.003, respectively). Periodontitis patients with rs1333048 AA-genotype showed higher levels of hsCRP than those carrying the minor C allele (median: 4.5 mg/L vs. 1.6 mg/L, p_adjusted = 0.007). This study is the first to show that, in addition to gender and BMI, also a leading SNP in ANRIL is explanatory for inter-individual variation in hsCRP levels in periodontitis patients of North European descent.     

Comparison and Analysis of Zinc and Cobalt-Based Systems as Catalytic Entities for the Hydration of Carbon Dioxide

In nature, the zinc metalloenzyme carbonic anhydrase II (CAII) efficiently catalyzes the conversion of carbon dioxide (CO₂) to bicarbonate under physiological conditions. Many research efforts have been directed towards the development of small molecule mimetics that can facilitate this process and thus have a beneficial environmental impact, but these efforts have met very limited success. Herein, we undertook quantum mechanical calculations of four mimetics, 1,5,9-triazacyclododedacane, 1,4,7,10-tetraazacyclododedacane, tris(4,5-dimethyl-2-imidazolyl)phosphine, and tris(2-benzimidazolylmethyl)amine, in their complexed form either with the Zn²⁺ or the Co²⁺ ion and studied their reaction coordinate for CO₂ hydration. These calculations demonstrated that the ability of the complex to maintain a tetrahedral geometry and bind bicarbonate in a unidentate manner were vital for the hydration reaction to proceed favorably. Furthermore, these calculations show that the catalytic activity of the examined zinc complexes was insensitive to coordination states for zinc, while coordination states above four were found to have an unfavorable effect on product release for the cobalt counterparts.