Anti-AIDS agents. Part 58: synthesis and anti-HIV activity of 1-thia-di-O-(-)-camphanoyl-(+)-cis-khellactone (1-thia-DCK) analogues

Two 1-thia-DCK analogues (9a and 9b) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. Compound 9a showed excellent anti-HIV activity with an EC(50) value of 0.00012 microM and therapeutic index of 1408000. Compound 9b was less active with EC(50) and TI values of 3.11 microM and 62.3, respectively. The bioassay results indicated that thia-DCK analogues merit attention as potential HIV-1 inhibitors.     

Does lack of available suitable habitat explain the patchy distributions of rare calcicole fern species?

In Canada, as in many countries, a relatively large number of fern species occur in specialized habitats and have low numbers of known populations containing few individuals. It has been suggested that the distribution of ferns is mostly determined by factors of climate and habitat due to relatively low limitations in ferns for dispersal and establishment. Here, we attempt to explain whether the local patchy distribution of three calcicole fern species rare in Canada ( Asplenium ruta-muraria , Pellaea atropurpurea and Woodsia obtusa ) is due to a lack of available habitat. Analyses based on micro-scale differences between sites occupied by the ferns and nearby, unoccupied sites did not reveal any significant differences, thereby indicating that the rarity of these species is not entirely driven by the rarity of their microhabitat at a local scale. Our results suggest that the widely accepted premise that ferns are not limited by dispersal or establishment should be reconsidered, as such limitations are the only likely explanation for empty available and suitable habitat.     

Annual and intra-annual growth dynamics of <Emphasis Type="Italic">Myricaria elegans</Emphasis> shrubs in arid Himalaya

Key message

To disentangle complex drivers of Myricaria elegans growth in arid Himalaya, we combined tree-ring analysis with detailed dendrometer records. We found that the combination of winter frost, summer floods, and strong summer diurnal temperature fluctuations control annual and intra-annual growth dynamics. The relative importance of these drivers is, however, changing with ongoing climate change.

Abstract

High-mountain areas are among the most sensitive environments to climate change. Understanding how different organisms cope with ongoing climate change is now a major topic in the ecology of cold environments. Here, we investigate climate drivers of the annual and intra-annual growth dynamics of Myricaria elegans, a 3–6 m tall tree/shrub, in a high-elevation cold desert in Ladakh, a rapidly warming region in the NW Himalayas. As Myricaria forms narrow stands around glacier streams surrounded by the desert, we hypothesized that its growth between 3800 and 4100 m will be primarily limited by low temperatures and summer floods. We found that warmer and less snowy conditions in April and May enhance earlywood production. Latewood formation is mostly driven by the June–July temperatures (T). The positive effect of warmer summers on both annual and intra-annual growth is related to fluctuating daily T (from +30 to 0 °C). In particular, dendrometer measurements over a 2-year period showed that net daily growth increments increased when the summer night T remained above 6 °C. While high night T during generally cold desert nights promoted growth, high daytime T caused water stress and growth inhibition. The growth–temperature dependency has gradually weakened due to accelerated warming since the 1990s. In addition, positive latewood responses to high March precipitation during the colder 1960s–1980s have become negative during the warmer 1990s–2000s, reflecting an intensification of summer floods. Latewood width increased while earlywood width decreased from the 1990s, indicating a prolonged growing season and a higher risk of drought-induced embolism in earlywood vessels. Due to a multiplicity of environmental drivers including winter frost, intensified floods and strong summer diurnal T fluctuations, Myricaria growth is not controlled by a single climate parameter. Similar results are increasingly reported from other Himalayan treelines, showing that ongoing climate change will trigger complex and probably spatially variable responses in tree growth. Our study showed that these complex climatic signals can be disentangled by a combination of long-term data from tree-rings with detailed, but short-term, records from dendrometers.

     

Single-Electron-Transfer in the Reduction of 1, 2-Dioxetanes by Biologically Active Substrates

Substances of low oxidation potential, which can also make available protons and hydrogen atoms, e.g. phenothiazines. NADH, and ascorbic acid efficiently reduce 1, 2-dioxetanes to their vic-diols by single-electron-transfer; a significant side reaction is catalytic decomposition of dioxetanes into the corresponding ketone fragments     

Insensitivity of D-amino acid dehydrogenase synthesis to catabolic repression in dadR mutants of Salmonella typhimurium

It has been found that synthesis of D-amino acid dehydrogenase in Salmonella typhimurium is stimulated by cyclic AMP and crp gene product. This indicates that catabolic control of the dehydrogenase resembles other bacterial systems of catabolic repression. We have isolated S. typhimurium mutants, dadR, which are resistant to L-methionine-interference with D-histidine utilization and are able to utilize D-tryptophan as a precursor of L-tryptophan. Mapping data indicate that the dadR locus is closely linked to dadA coding for the structure of D-amino acid dehydrogenase. The synthesis of the dehydrogenase in dadR mutants is completely insensitive to the repression by glucose, but remains inducible by L-alanine. We conclude thereof that dadR mutants have changes in the promoter region which increase the expression of the dadA gene in the presence of glucose metabolism. A likely possibility that induction of the dad operon by alanine might be under positive control is discussed.     

Effect of Helium Gas at Elevated Pressure on Iron Transport and Growth of Escherichia coli

Helium at an ambient pressure of 68 at m with 0.2 atm of O(2) shortened by 1 to 1.5 h the lag phase for growth of Escherichia coli in minimal medium supplemented with 2 muliters of cell-free culture filtrate (CFF) per ml or with 1 muM 2,3-dihydroxybenzoylserine (DHBS), an iron chelator. The lag phase of cultures not exposed to helium could be shortened by use of supplements, but higher concentrations were required-10 to 30 muliters of CFF per ml or 10 to 50 muM DHBS. Strain AN 193 of E. coli, which requires the DHBS precursor 2,3-dihydroxybenzoic acid (DHBA), grew well in media with 10 muM DHBA when exposed to helium at 68 atm, whereas 100 muM DHBA was required for growth in unexposed cultures. In the presence of 100 muM DHBA plus 1.0 muM ethylenediaminetetraactic acid, growth was inhibited at 1 and 68 atm. Growth was restored, however, by the addition of 0.1 muM FeSO(4) at 68 atm and 1.0 muM FeSO(4) at 1 atm, but lag times were invariably shorter in the pressurized cultures. Hydrostatic pressures of 68 atm did not reduce the lag phase in the presence of CFF, DHBS, or DHBA. Our results suggest that 68 atm of helium pressure, but not hydrostatic pressure, elicited a more rapid transport of iron into the cells.     

Experimental allergic orchitis: the isolation and partial characterization of an aspermatogenic polypeptide (AP3) with an apparent sequential disease-inducing determinant(s)

An aspermatogenic polypeptide (AP3) capable of inducing experimental allergic orchitis (EAO) in the guinea pig (GP) was purified from GP testes by sequential delipidation, acid extraction, pH precipitation, ammonium sulfate fractionation, trichloroacetic acid precipitation, gel filtration on Sephadex G-75, preparative isoelectric focusing from pH 3-10 followed by isoelectric focusing from pH 7-10, gel filtration on Sephadex G-75 Superfine under reducing conditions, and reduced acid urea gel electrophoresis. Approximately 250 micrograms (BSA equivalents) of AP3 were obtained from 500 g wet weight of GP testes. On 15% reduced acid urea polyacrylamide gels, AP3 appeared as a single band with an Rf of 0.19. SDS-PAGE showed a single band with a mobility corresponding to a m.w. of 12,500 +/- 1500. The isoelectric point, determined during purification, was 9.90 +/- 0.50. Amino acid analysis of AP3 indicates it is a protein. Gas liquid chromatographic analysis failed to reveal the presence of either hexose or hexosamine, indicating that AP3 is probably not a glycopeptide. Two to 5.0 micrograms (BSA equivalents) of AP3 are capable of inducing severe EAO in 100% of GP tested; 1 to 2.0 micrograms (BSA equivalents) induced EAO in 60% of GP tested. Because AP3 appears to be nonglycosylated and the aspermatogenic activity of AP3 is highly resistant to various denaturing conditions including reduction and alkylation, the primary sequence of the polypeptide rather than higher ordered structure may be more important in defining the determinant(s) responsible for its aspermatogenic activity.