Investigations on the biosynthesis of steroids and terpenoids: XI. The 24-methylene sterol 24(28)-reductase of Saccharomyces cerevisiae

The microsomal fraction of Saccharomyces cerevisiae has been shown to catalyse the NADPH-dependent reduction of ergosta-5,7,22,24(28)-tetraen-3β-ol to ergosterol. This cell-free system together with whole-cell cultures of polyene-resistant mutants has been used to compare the rates of reduction of other 24-methylene sterols. The results indicate that the enzyme involved exhibits a marked specificity for ergosta-5,7,22,24(28)-tetraen-3β-ol and support the concept of a major terminal step in ergosterol biosynthesis.     

Isolation and identification of products from alkylation of nucleic acids: ethyl- and isopropyl-purines.

Ethylation and isopropylation of guanine in alkaline solution, or of adenine in formic acid, by alkyl methanesulphonates gave the following products: 1-, N2-, 3-, O6-, 7- and 9-alkylguanines; 1-, 3-, 7- and 9-alkyladenines. The products were identified from their characteristic u.v-absorption spectra, by comparison with either known ethyladenines or with the corresponding known methyladenines, and were also characterized by mass spectrometry. Their chromatographic properties on paper, t.l.c. and various columns were determined. DNA was alkylated in neutral solution with 14C-labelled alkyl methanesulphonates and the ratios of the alkylpurines formed were obtained, and compared for alkylation by methyl, ethyl and isopropyl methanesulphonates and by N-methyl-N-nitrosourea. The extents of alkylation at O-6 of guanine relative to those at N-7 of guanine varied with the reactivity of the methylating agents according to the predictions of Swain & Scott (1953) relating nucleophilicity of the groups alkylated with the substrate constants of the alkylating agents. The relative extents of alkylation at N-3 of adenine did not follow this correlation.     

New Natural Noncannabinoid Ligands for Cannabinoid Type-2 (CB2) Receptors

Since the discovery that Δ ⁹-tetrahydrocannabinol and related cannabinoids from Cannabis sativa L. act on specific physiological receptors in the human body and the subsequent elucidation of the mammalian endogenous cannabinoid system, no other natural product class has been reported to mimic the effects of cannabinoids. We recently found that N-alkyl amides from purple coneflower (Echinacea spp.) constitute a new class of cannabinomimetics, which specifically engage and activate the cannabinoid type-2 (CB₂) receptors. Cannabinoid type-1 (CB₁) and CB₂ receptors belong to the family of G protein-coupled receptors and are the primary targets of the endogenous cannabinoids N-arachidonoyl ethanolamine and 2-arachidonoyl glyerol. CB₂ receptors are believed to play an important role in distinct pathophysiological processes, including metabolic dysregulation, inflammation, pain, and bone loss. CB₂ receptors have, therefore, become of interest as new targets in drug discovery. This review focuses on N-alkyl amide secondary metabolites from plants and underscores that this group of compounds may provide novel lead structures for the development of CB₂-directed drugs.     

Frequent In-Migration and Highly Focal Transmission of Dengue Viruses among Children in Kamphaeng Phet,Thailand

Revealing the patterns and determinants of the spread of dengue virus (DENV) at local scales is central to understanding the epidemiology and evolution of this major human pathogen. We performed a phylogenetic analysis of the envelope (E) genes of DENV-1, -2, -3, and -4 isolates (involving 97, 23, 5, and 74 newly collected sequences, respectively) sampled from school-based cohort and village-based cluster studies in Kamphaeng Phet, Thailand, between 2004 and 2007. With these data, we sought to describe the spatial and temporal patterns of DENV spread within a rural population where a future vaccine efficacy trial is planned. Our analysis revealed considerable genetic diversity within the study population, with multiple lineages within each serotype circulating for various lengths of time during the study period. These results suggest that DENV is frequently introduced into both semi-urban and rural areas in Kamphaeng Phet from other populations. In contrast, the persistence of viral lineages across sampling years was observed less frequently. Analysis of phylogenetic clustering indicated that DENV transmission was highly spatially and temporally focal, and that it occurred in homes rather than at school. Overall, the strength of temporal clustering suggests that seasonal bottlenecks in local DENV populations facilitate the invasion and establishment of viruses from outside of the study area, in turn reducing the extent of lineage persistence.     

Modeling mate-finding behavior of the swarming polychaete,Nereis succinea,with TangoInSilico,a scientific orkflow-based simulation system for sexual searching

Summary

Pheromones can be used as attractants for the opposite sex in many environments; however, little is known about the search strategies employed in responding to pheromones in the marine environment. The spawning behavior of males of the polychaete Nereis succinea is known to be triggered at close range by a high concentration (>～10^?7 M) of pheromone, cysteine glutathione disulfide (CSSG), released by females. Since CSSG also causes acceleration of swimming and increased turning, in addition to eliciting ejaculation, we proposed the hypothesis that these behaviors elicited by low concentrations of pheromone can be used by males to find females. The current study develops a computer simulation model of male and female N. succinea behavior for testing whether male responses to low concentrations of CSSG can facilitate finding females. Video recording of female swimming behavior in the field showed spontaneous loops, spirals, and circles that have been incorporated into the model. The scientific workflow paradigm within which the computer model has been developed also incorporates a data provenance system to enable systematic replay and testing of responses to individual parameters. Output of the model shows complex turning behavior leading to successful mating encounters at concentrations as low as 3×10^?9 M CSSG. Behavior resembling the output of the model was recorded in field observations. Application of the model in the future will be used to determine what pheromone concentrations produce significant increases in the probability of mating encounters.     

Biometry of Cenomanian–Turonian placoliths: a proxy for changes of fertility and surface‐water temperature?

Most publications discussing Cenomanian–Turonian calcareous nannofossils focus on abundance fluctuations across the boundary interval. So far, there have been no studies that deal with the influence of palaeoenvironmental changes on the size of common Cenomanian–Turonian nannofossil taxa. The genera Biscutum, Broinsonia, Prediscosphaera, Retecapsa and Watznaueria have therefore been analysed from 19 samples of Cenomanian–Turonian age from the Goban Spur, northeast Atlantic. The genus Biscutum shows a slight decrease of mean length from 4.14 μm in the Cenomanian to 3.94 μm in the Turonian. Broinsonia is marked by a decrease from 6.07 μm in the Cenomanian to 5.64 μm in the Turonian. On the other hand, Prediscospheara increases in size from 4.98 μm in the Cenomanian to 5.61 μm in the Turonian. Two genera (Retecapsa, Watznaueria) show no significant changes in their mean length. The mean size of Biscutum is perhaps controlled by nutrients, where larger specimens may have preferred the more fertile palaeoenvironment of the Late Cenomanian. The size decrease of Biscutum in the Turonian is probably related to reduced nutrient availability. The genus Prediscosphaera spp., may have favoured low‐fertility conditions, as its mean size increases in the Turonian. A worldwide decline of the frequency of Broinsonia spp. during the Cenomanian–Turonian transition implies that this genus is not solely controlled by the nutrient content. The size of Broinsonia spp. may have been therefore influenced by the latest Cenomanian warming event. The increase in sea‐surface temperature may have been unfavourable for Broinsonia spp. as reflected by decreasing mean size and frequency. □Calcareous nannofossils, biometry, morphometry, Oceanic Anoxic Event 2.     

Phylogenetic analysis reveals that Rhabdopleura is an extant graptolite

A phylogenetic analysis of morphological data from modern pterobranch hemichordates (Cephalodiscus, Rhabdopleura) and representatives of each of the major graptolite orders reveals that Rhabdopleura nests among the benthic, encrusting graptolite taxa as it shares all of the synapomorphies that unite the graptolites. Therefore, rhabdopleurids can be regarded as extant members of the Subclass Graptolithina (Class Pterobranchia). Combined with the results of previous molecular phylogenetic studies of extant deuterostomes, these results also suggest that the Graptolithina is a sister taxon to the Subclass Cephalodiscida. The Graptolithina, as an important component of Early–Middle Palaeozoic biotas, provide data critical to our understanding of early deuterostome phylogeny. This result allows one to infer the zooid morphology, mechanics of colony growth and palaeobiology of fossil graptolites in direct relation to the living members of the clade. The Subdivision Graptoloida (nom. transl.), which are all planktic graptolites, is well supported in this analysis. In addition, we recognize the clade Eugraptolithina (nov.). This clade comprises the Graptoloida and all of the other common and well‐known graptolites of the distinctive Palaeozoic fauna. Most of the graptolites traditionally regarded as tuboids and dendroids appear to be paraphyletic groups within the Eugraptolithina; however, Epigraptus is probably not a member of this clade. The Eugraptolithina appear to be derived from an encrusting, Rhabdopleura‐like species, but the available information is insufficient to resolve the phylogeny of basal graptolites. The phylogenetic position of Mastigograptus and the status of the Dithecoidea and Mastigograptida also remain unresolved. □ Biodiversity, Cambrian, Hemichordata, Deuterostomia, Ordovician.     

Somatoform disorders among patients attending walk-in clinics in Trinidad: prevalence and association with depression and anxiety

Objectives Somatoform disorders are common in international primary care settings, but have been little studied in the developing world. The objective of this study was to determine the prevalence of severe undifferentiated somatoform disorder, and its relationship to depression and anxiety, among patients attending walk-in clinics in Trinidad.Methods The study participants, who were all aged 18 years or older and attending walk-in clinics at 16 randomly selected health centres, were surveyed between May and August 2007 using the PRIME-MD questionnaire.Results There were 594 participants (the response rate was 92%), of whom 72.7% were female. Their ages ranged from 18 to 93 years, and 54.5% were over 50 years of age. In total, 37.2% were married and 25.9% were single. Indo-Trinidadians represented 43.1% and Afro-Trinidadians represented 36% of the study sample; 56.5% of the participants reported that their income was less than US$ 400 per month, and 65.7% were unemployed. At walk-in clinics in Trinidad, the estimated prevalence of severe undifferentiated somatoform disorder was 10.3% (95% CI: 7.86–12.74), that of hypochondriasis was 28.5% (95% CI: 24.9–32.1), and that of body dysmorphic disorder was 15.8% (95% CI: 11.9–18.7). Severe undifferentiated somatoform disorder was statistically significantly associated with gender and ethnicity but not with age, level of education, employment status or income. Chi-square testing found significant associations between the presence of severe undifferentiated somatoform disorder and both depression and anxiety (P < 0.05), between hypochondriasis and both anxiety and depression (P < 0.05), and between body dysmorphic disorder and depression (P < 0.05) but not anxiety. Regression analysis suggested that the demographic features that predicted severe undifferentiated somatoform disorder were being female or Indo-Trinidadian.Conclusions Walk-in clinics in Trinidad that serve older patients on a lower income have a high proportion of patients with somatoform disorders as measured by the PRIME-MD scale. These patients exhibit many features of anxiety and depression. These findings have implications for medical training and service delivery.