Time Space Translation: A Hox Mechanism for Vertebrate A-P Patterning

The vertebrate A-P axis is a time axis. The head is made first and more and more posterior levels are made at later and later stages. This is different to the situation in most other animals, for example, in Drosophila. Central to this timing is Hox temporal collinearity (see below). This occurs rarely in the animal kingdom but is characteristic of vertebrates and is used to generate the primary axial Hox pattern using time space translation and to integrate successive derived patterns (see below). This is thus a different situation than in Drosophila, where the primary pattern guiding Hox spatial collinearity is generated externally, by the gap and segmentation genes.     

Binding affinities of CRBPI and CRBPII for 9-cis-retinoids

Background

Cellular retinol binding-protein I (CRBPI) and cellular retinol binding-protein II (CRBPII) serve as intracellular retinoid chaperones that bind retinol and retinal with high affinity and facilitate substrate delivery to select enzymes that catalyze retinoic acid (RA) and retinyl ester biosynthesis. Recently, 9-cis-RA has been identified in vivo in the pancreas, where it contributes to regulating glucose-stimulated insulin secretion. In vitro, 9-cis-RA activates RXR (retinoid × receptors), which serve as therapeutic targets for treating cancer and metabolic diseases. Binding affinities and structure–function relationships have been well characterized for CRBPI and CRBPII with all-trans-retinoids, but not for 9-cis-retinoids. This study extended current knowledge by establishing binding affinities for CRBPI and CRBPII with 9-cis-retinoids.

Methods

We have determined apparent dissociation constants, K′_d, through monitoring binding of 9-cis-retinol, 9-cis-retinal, and 9-cis-RA with CRBPI and CRBPII by fluorescence spectroscopy, and analyzing the data with non-linear regression. We compared these data to the data we obtained for all-trans- and 13-cis-retinoids under identical conditions.

Results

CRBPI and CRBPII, respectively, bind 9-cis-retinol (K′_d, 11 nM and 68 nM) and 9-cis-retinal (K′_d, 8 nM and 5 nM) with high affinity. No significant 9-cis-RA binding was observed with CRBPI or CRBPII.

Conclusions

CRBPI and CRBPII bind 9-cis-retinol and 9-cis-retinal with high affinities, albeit with affinities somewhat lower than for all-trans-retinol and all-trans-retinal.

General significance

These data provide further insight into structure–binding relationships of cellular retinol binding-proteins and are consistent with a model of 9-cis-RA biosynthesis that involves chaperoned delivery of 9-cis-retinoids to enzymes that recognize retinoid binding-proteins.     

Catabolic and Genetic Diversity of Degradative Bacteria from Fuel-Hydrocarbon Contaminated Aquifers

Abstract Subsurface sediments were recovered from two aquifers contaminated with petroleum hydrocarbons in order to isolate and characterize indigenous microorganisms capable of biodegrading fuel-related compounds. These sediments had been previously studied using catabolic gene probes providing putative demonstration of significant biodegradation potential. Based on 16S rDNA sequence analysis, the isolates were phylogenetically similar to common soil microorganisms, including members of the genera Pseudomonas, Ralstonia, Burkholderia, Sphingomonas, Flavobacterium, and Bacillus. A total of 26 isolates were obtained using a vapor-plate enrichment technique with the volatile aromatic hydrocarbons toluene, ethylbenzene, p-xylene, naphthalene, and JP-4 jet fuel. JP-4, toluene, and ethylbenzene served as growth substrates for more than 80% of the isolates, while less than 10% of the organisms grew on the aromatic compounds benzene and o-xylene. Subsequent assays monitoring the evolution of ¹⁴CO2 indicated that only seven isolates were able to completely mineralize target compounds. One isolate, designated CAFB-naph-5, was able to completely mineralize the monoaromatic compounds salicylate and toluene, as well as the polyaromatic compound naphthalene. Molecular probing of the isolates showed four isolates hybridized with DNA probes targeting genes commonly associated with hydrocarbon-degrading bacteria. The isolates also demonstrated broad ability to grow in the presence of the antimicrobial agents streptomycin, tetracycline rifampicin, carbenicillin, nalidixic acid, kanamycin, and ampicillin. The results of the study demonstrate the biochemical and biodegradative capabilities of microorganisms isolated from contaminated aquifer systems and provide closure for indirect molecular monitoring of degradative potential in contaminated environments.     

Food choice causes interrupted feeding in the generalist grasshopper Schistocerca americana: further evidence for inefficient decision-making

Individual grasshoppers were observed foraging on either single food plant species or binary mixtures of them. Individuals ate slightly less on the mixtures, but grew faster on them. In the mixtures, individuals fed regularly from both plant species, typically eating both within a single meal. Feeding bouts were longer on the preferred plant species in the mixture. The pattern of foraging behavior was markedly different in mixtures and single food treatments. In mixtures, although the total length of time engaged in ingestion over the day was slightly less than in single food treatments, there were relatively more short feeding bouts and more gaps between feeding bouts within meals, so that the time spent in activities associated with the food was markedly longer on mixtures. This is discussed in terms of efficiency and the problem of choice that faces individual generalists. The efficiency factor and its impact on vigilance is added to the other costs of being a polyphagous herbivore.     

Effects of weather and season on the summer activity of dormice Muscardinus avellanarius

Activity schedules of dormice were investigated in relation to weather and seasonal factors, by automatic monitoring of temperatures in nests of free-living animals. Data were obtained for two years and 294 dormouse-nights. The principal exogenous factor influencing pan-seasonal activity was photoperiod, activity beginning about 30 min after sunset and ending about 50 min before sunrise. However, on a seasonal scale, activity start time, end time and length were all strongly affected by ambient temperature and rainfall; higher temperatures appeared to lengthen activity, whereas rainfall reduced it. Diurnal activity was rare and took place when ambient air temperatures at midnight fell below 9°C. There were large differences in activity shedules between years, which were also correlated with weather conditions. Dormice are directly affected by weather, which also strongly influences the availability of their food. Weather may in general heavily influence small hibernators, because they can utilise facultative torpor to overcome adverse conditions. Our results imply that weather may have a profound effect on dormouse life history, especially in Britain's maritime climate where summers are frequently cool and wet.     

Effect of trapidil derivative AR 12456 on intracellular cholesterol homeostasis in human hepatoma cell line Hep G2

The effect of trapidil derivative AR12456 on intracellular cholesterol metabolism was investigated in human hepatoma cell line HepG2. AR12456 enhanced the uptake and degradation of¹²⁵I-LDL in a dose-dependent manner. The drug inhibited cholesterol synthesis and esterification without affecting cellular cholesterol content and bile acid synthesis; cholesterol efflux was slightly increased. These results show that the inhibition of cholesterol synthesis together with the enhanced expression of LDL receptors may partially explain the hypocholesterolemic activity of compound AR12456.