Aminoadamantanes containing monoterpene-derived fragments as potent tyrosyl-DNA phosphodiesterase 1 inhibitors

The ability of a number of nitrogen-containing compounds that simultaneously carry the adamantane and monoterpene moieties to inhibit Tdp1, an important enzyme of the DNA repair system, is studied. Inhibition of this enzyme has the potential to overcome chemotherapeutic resistance of some tumor types. Compound (+)-3c synthesized from 1-aminoadamantane and (+)-myrtenal, and compound 4a produced from 2-aminoadamantane and citronellal were found to be most potent as they inhibited Tdp1 with IC₅₀ values of 6 and 3.5 µM, respectively. These compounds proved to have low cytotoxicity in colon HCT-116 and lung A-549 human tumor cell lines (CC₅₀ > 50 µM). It was demonstrated that compound 4a at 10 µM enhanced cytotoxicity of topotecan, a topoisomerase 1 poison in clinical use, against HCT-116 more than fivefold and to a lesser extent of 1.5 increase in potency for A-549.     

Expression of micF involved in porin synthesis in Escherichia coli: two distinct cis-acting elements respectively regulate micF expression positively and negatively

micF RNA, whose sequence is highly complementary to a 5'-portion of ompF mRNA, has been implicated in the osmoregulation and thermoregulation of the ompF porin gene in Escherichia coli. To define and characterize cis-acting regulatory regions upstream of the micF promoter, a series of deletions of the micF promoter fused to the lacZ gene were constructed. Two distinct regions, which function differently, were identified as cis-acting regulatory elements, namely, one responsible for OmpR-dependent activation and the other for OmpR-independent repression of micF expression. The former contains the OmpR-binding site, which simultaneously regulates both the genes, micF and ompC, in response to the medium osmolarity. The latter may be involved in an unknown regulatory process of micF expression.     

Chemical constituents of the roots of Scorzonera divaricata and their chemotaxonomic significance

The phytochemical study of the roots of Scorzonera divaricata Turcz led to the isolation of 27 compounds, including eight sterols (1–8), one lignan (9), two cumarins (10, 11), five phenylpropanoids (12–16), six benzene derivatives (17–22), methyl-β-D-fructofuranoside (23), monolinolein (24), and three aliphatic acids (25–27). The structures of isolated compounds were identified using NMR and ESI-MS spectroscopic methods and comparing them with those previously reported. Except for β-daucosterol (8), scopoletin (10) and caffeic acid (16) from S. divaricata, this is the first report of the other 24 compounds from S. divaricata. Among them, eleven compounds (2–6, 11, 17, 19, 20, 23, 25) were reported from genus Scorzonera for first time, suggesting that they could be used to distinguish S. divaricata from the other species of Scorzonera. Furthermore, the chemotaxonomic significance of isolated compounds from S. divaricata has also been discussed.     

The importance of chemical environmental cues for juvenile Lethrinus nebulosus Forsskål (Lethrinidae, Teleostei) when settling into their first benthic habitat

A commercially important coral-reef fish, the spangled emperor Lethrinus nebulosus, settles into seagrass beds at the end of its pelagic larval phase, but the mechanism for locating these beds is unknown. To investigate this mechanism we first used a wide-choice, ex situ setup to examine the ability of captivity-reared naïve L. nebulosus settlers to select their first benthic habitat by reference to chemical cues. Second, we examined the morphology and ultrastructure of the nasal olfactory organ in settling L. nebulosus juveniles. We obtained the first evidence of a tropical seagrass-settling coral reef fish that can use chemical environmental cues in selecting its first benthic habitat at ranges up to at least 2 m. The L. nebulosus settlers exhibited a well developed pair of nasal olfactory organs, positioned in nares on the dorsal side of the head. These organs were elliptical radial rosettes, one in each of the olfactory chambers, and each comprised 12 lamellae, six on each side of a midline raphe, which were totally covered with sensory and non-sensory cilia, except for the margins. This type of cilia distribution is thought to indicate an acute sense of smell. The olfactory epithelium contained mature and immature ciliated receptor neurons bearing three to five cilia, and a second type of receptor neuron bearing six to eight microvilli.     

PERSPECTIVE: THE THEORIES OF FISHER AND WRIGHT IN THE CONTEXT OF METAPOPULATIONS: WHEN NATURE DOES MANY SMALL EXPERIMENTS

We critically review the two major theories of adaptive evolution developed early in this century, Wright's shifting balance theory and Fisher's large population size theory, in light of novel findings from field observations, laboratory experiments, and theoretical research conducted over the past 15 years. Ecological studies of metapopulations have established that the processes of local extinction and colonization of demes are relatively common in natural populations of many species and theoretical population genetic models have shown that these ecological processes have genetic consequences within and among local demes. Within demes, random genetic drift converts nonadditive genetic variance into additive genetic variance, increasing, rather than limiting, the potential for adaptation to local environments. For this reason, the genetic differences that arise by drift among demes, can be augmented by local selection. The resulting adaptive differences in gene combinations potentially contribute to the genetic origin of new species. These and other recent findings were not discussed by either Wright or Fisher. For example, although Wright emphasized epistatic genetic variance, he did not discuss the conversion process. Similarly, Fisher did not discuss how the average additive effect of a gene varies among demes across a metapopulation whenever there is epistasis. We discuss the implications of such recent findings for the Wright-Fisher controversy and identify some critical open questions that require additional empirical and theoretical study.     

Respiratory components in acidophilic bacteria that respire on iron

Abstract

Microorganisms capable of aerobic respiration on ferrous ions are spread throughout eubacterial and archaebacterial phyla. Phylogenetically distinct organisms were shown to express spectrally distinct redox‐active biomolecules during autotrophic growth on soluble iron. A new iron‐oxidizing eubacterium, designated as strain Funis, was investigated. Strain Funis was judged to be different from other known iron‐oxidizing bacteria on the bases of comparative lipid analyses, 16S rRNA sequence analyses, and cytochrome composition studies. When grown autotrophically on ferrous ions, Funis produced conspicuous levels of a novel acid‐stable, acid‐soluble yellow cytochrome with a distinctive absorbance peak at 579 nm in the reduced state.

Stopped‐flow spectrophotometric kinetic studies were conducted on respiratory chain components isolated from cell‐free extracts of Thiobacillus ferrooxidans. Experimental results were consistent with a model where the primary oxidant of ferrous ions is a highly aggregated c‐type cytochrome that then reduces the periplasmic rusticyanin. The Fe(II)‐dependent, cytochrome c‐catalyzed reduction of the rusticyanin possessed three kinetic properties in common with corresponding intact cells that respire on iron: the same anion specificity, a similar dependence of the rate on the concentration of ferrous ions, and similar rates at saturating concentrations of ferrous ions