Differential depressant effects of general anesthetics on the cardiovascular response to cocaine in mice.

In recent years, murine models have gained increasing importance for studies of cardiovascular physiology and pharmacology, largely due to the development of transgenic strains with specific alterations in phenotype. Differential effects of general anesthetic agents on the cardiovascular responses to cocaine have been reported in larger mammals; therefore, we studied the effects of commonly used anesthetics on heart function and on blood pressure responses to cocaine in Swiss Webster mice. We positioned a polyethylene catheter (PE-10) in the right carotid artery or left ventricle of mice anesthetized with equivalent anesthetic dose of either ketamine-xylazine (KX, 40 mg/kg + 5 mg/kg), pentobarbital (PEN, 40 mg/kg) or alpha-chloralose-urethane (CU, 80 mg/kg + 100 mg/kg). Cocaine (0.3 mg/kg, 1 mg/kg and 3 mg/kg) was administrated via the left jugular vein by bolus injection. In the KX group, the basal mean arterial pressure (MAP) and systolic left ventricular pressure (LVP) were 110 +/- 12 and 120 +/- 13 mmHg, respectively, close to conscious values. However, PEN and CU significantly decreased the basal parameters (P < 0.01 compared to the KX group). The lowest dose of cocaine (0.3 mg/kg) elicited minimal changes. Significant responses were obtained with a 1-mg/kg dose of cocaine (P < 0.01 compared to baseline). However, at 3 mg/kg, a toxic effect of cocaine appeared in all three anesthetic groups. Compared to published conscious animal data, anesthetic agents attenuated the cardiovascular effects of cocaine. Taken together, our results indicate that minimally effective doses of general anesthetics may significantly alter the basal hemodynamic state and the responses to sympathomimetic agents in the murine model, as has been reported in larger mammalian species. We concluded that anesthesia with ketamine-xylazine provides baseline hemodynamic values close to reported values in conscious animals, but also attenuates the hemodynamic response to cocaine.     

Correlation between the number of adult male Pectinophora gossypiella (Saund.) (Lep., Gelechidae) catches on pheromone traps and the rate of infestation in fruiting bodies of cotton plants by young larvae in three regions of central Greece

In order to evaluate the influence of the number of catches in pheromone-baited traps on the percentage of larval infestation, six delta traps equipped with sex attractant were placed in each of three regions in Central Greece (Farkadona, Farsala, Almyros) in cotton fields from 20 June until 30 September 1995. The collection of fruiting bodies took place weekly and the counting of adults in the traps was carried out each day. The population fluctuation in all three regions was similar with their peak during the first weeks of August. In Farkadona the infestation level was low (1% at the first sampling of August) with a maximum of 9% in the last sampling of September. In Farsala and Almyros, the infestation level was already high (10% and above) in early August. There was a significant positive linear correlation between the number of moth catches and the infestation percentage from first- and second-stage larvae on the first (R = 0694) and second (R = 0.7399) boll-feeding generations.     

A highly conserved signal controls degradation of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase in eukaryotes.

Sterol synthesis by the mevalonate pathway is modulated, in part, through feedback-regulated degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). In both mammals and yeast, a non-sterol isoprenoid signal positively regulates the rate of HMGR degradation. To define more precisely the molecule that serves as the source of this signal, we have conducted both pharmacological and genetic manipulations of the mevalonate pathway in yeast. We now demonstrate that farnesyl diphosphate (FPP) is the source of the positive signal for Hmg2p degradation in yeast. This FPP-derived signal does not act by altering the endoplasmic reticulum degradation machinery in general. Rather, the FPP-derived signal specifically modulates Hmg2p stability. In mammalian cells, an FPP-derived molecule also serves as a positive signal for HMGR degradation. Thus, both yeast and mammalian cells employ the same strategy for regulation of HMGR degradation, perhaps by conserved molecular processes.     

Host age and fitness-related traits in a koinobiont aphid parasitoid

Abstract.  1. Trade-offs play a key role in species evolution and should be found in host–parasitoid interactions where the host quality may differ between host age categories.
2. The braconid wasp, Aphidius ervi , is a solitary endoparasitoid that allows its aphid hosts to continue to feed and grow after parasitisation. The hypotheses that host age influences their quality and that female parasitoids exploit their hosts based on that quality were tested under laboratory conditions using no-choice tests.
3.  Aphidius ervi females accepted the aphid Myzus persicae for oviposition and their progeny developed successfully in all host ages. The fitness-related traits of parasitoids did not increase linearly with the host age in which they developed. Host quality was found to be optimal at intermediate host ages and the females preferred to parasitise these hosts. The shortest progeny development time and a more female-biased sex ratio were observed in hosts of intermediate age.
4. This study suggests the existence of multiple interactive trade-offs occurring during host–parasitoid interactions according to host age related quality.     

Benzimidazole- and benzoxazole-based inhibitors of Rho kinase

Inhibitors of Rho kinase have been developed based on two distinct scaffolds, benzimidazoles, and benzoxazoles. SAR studies and efforts to optimize the initial lead compounds are described. Novel selective inhibitors of ROCK-II with excellent potency in both enzyme and cell-based assays were obtained. These inhibitors possess good microsomal stability, low cytochrome P-450 inhibitions and good oral bioavailability.     

Genetic relatedness in wintering groups of house sparrows (Passer domesticus)

Social behaviour of group-living animals is often influenced by the relatedness of individuals, thus understanding the genetic structure of groups is important for the interpretation of costs and benefits of social interactions. In this study, we investigated genetic relatedness in feeding aggregations of free-living house sparrows ( Passer domesticus ) during the nonbreeding season. This species is a frequent model system for studies of social behaviour (e.g. aggression, social foraging), but we lack adequate information on the kin structure of sparrow flocks. During two winters, we ringed and observed sparrows at feeding stations, and used resightings to identify stable flock-members and to calculate association indices between birds. We genotyped the birds using seven highly polymorphic microsatellite loci, and estimated pairwise relatedness coefficients and relatedness categories (close kin vs. unrelated) by maximum likelihood method. We found that most birds were unrelated to each other in the flocks (mean ± SE relatedness coefficient: 0.06 ± 0.002), although most individuals had at least a few close relatives in their home flock (14.3 ± 0.6% of flock-mates). Pairwise association between individuals was not significantly related to their genetic relatedness. Furthermore, there was no difference between within-flock vs. between-flock relatedness, and birds had similar proportions of close kin within and outside their home flock. Finally, relatedness among members of different flocks was unrelated to the distance between their flocks. Thus, sparrow flocks were not characterized by association of relatives, nevertheless the presence of some close kin may provide opportunity for kin-biased behaviours to evolve.     

Affinity maturation and characterization of a human monoclonal antibody against HIV-1 gp41

The human D5 monoclonal antibody binds to the highly conserved hydrophobic pocket on the N-terminal heptad repeat (NHR) trimer of HIV-1 gp41 and exhibits modest yet relatively broad neutralization activity. Both binding and neutralization depend on residues in the complementarity determining regions (CDRs) of the D5 IgG variable domains on heavy chain (VH) and light chain (VL). In an effort to increase neutralization activity to a wider range of HIV-1 strains, we have affinity matured the parental D5 scFv by randomizing selected residues in 5 of its 6 CDRs. The resulting scFv variants derived from four different CDR changes showed enhanced binding affinities to gp41 NHR mimetic (5-helix) which correlated to improved neutralization potencies by up to 8-fold. However, when converted to IgG1s, these D5 variants had up to a 12-fold reduction in neutralization potency over their corresponding scFvs despite their slightly enhanced in vitro binding affinities. Remarkably, D5 variant IgG1s bearing residue changes in CDRs that interact with epitope residues N-terminal to the hydrophobic pocket (such as VH CDR3 and VL CDR3) retained more neutralization potency than those containing residue changes in pocket-interacting CDRs (such as VH CDR2). These results provide compelling evidence for the existence of a steric block to an IgG that extends to the gp41 NHR hydrophobic pocket region, and can be a useful guide for developing therapeutic antibodies and vaccines circumventing this block.     

Structure and diversity of the Mesozoic wood genus Xenoxylon in Far East Asia: implications for terrestrial palaeoclimates

Although the faunal elements of Far East Asian Mesozoic terrestrial biota have attracted much attention in recent years, their palaeoecology remains poorly known. In particular, features of the palaeoclimate are highly controversial. To address this point we used the Mesozoic fossil wood Xenoxylon , a genus recognized as an indicator of wet temperate biotopes and which is common in the area during the Carnian–Maastrichtian interval. We re-appraised bibliographic data and gathered new data for Xenoxylon in the Mesozoic of Far East Asia. This demonstrated that previous taxonomic approaches to the genus have been so far idiosyncratic. We examined the anatomical diversity of morphogenus Xenoxylon in Far East Asia and compared it to that of samples from Europe. This indicates that in an area centred on north-eastern China, Xenoxylon reached a level of anatomical diversity unmatched elsewhere in the world. We hypothesize that this diversity witnesses the persistence of palaeoecological conditions particularly suitable for Xenoxylon and that a wet temperate climate prevailed over most of the area throughout the Carnian–Maastrichtian interval. It is in this setting that the famous Jehol Biota probably evolved.     

GeneComps and ChemComps: a new CTD metric to identify genes and chemicals with shared toxicogenomic profiles

The Comparative Toxicogenomics Database is a public resource that promotes understanding about the effects of environmental chemicals on human health. Currently, CTD describes over 184,000 molecular interactions for more than 5,100 chemicals and 16,300 genes/proteins. We have leveraged this dataset of chemical-gene relationships to compute similarity indices following the statistical method of the Jaccard index. These scores are used to produce lists of comparable genes (“GeneComps”) or chemicals (“ChemComps”) based on shared toxicogenomic profiles. GeneComps and ChemComps are now provided for every curated gene and chemical in CTD. ChemComps are particularly significant because they provide a way to group chemicals based upon their biological effects, instead of their physical or structural properties. These metrics provide a novel way to view and classify genes and chemicals and will help advance testable hypotheses about environmental chemical-genedisease networks.

Availability

CTD is freely available at http://ctd.mdibl.org/     

Temperature adaptation of soil bacterial communities along an Antarctic climate gradient: predicting responses to climate warming

Soil microorganisms, the central drivers of terrestrial Antarctic ecosystems, are being confronted with increasing temperatures as parts of the continent experience considerable warming. Here we determined short‐term temperature dependencies of Antarctic soil bacterial community growth rates, using the leucine incorporation technique, in order to predict future changes in temperature sensitivity of resident soil bacterial communities. Soil samples were collected along a climate gradient consisting of locations on the Antarctic Peninsula (Anchorage Island, 67 °34′S, 68 °08′W), Signy Island (60 °43′S, 45 °38′W) and the Falkland Islands (51 °76′S 59 °03′W). At each location, experimental plots were subjected to warming by open top chambers (OTCs) and paired with control plots on vegetated and fell‐field habitats. The bacterial communities were adapted to the mean annual temperature of their environment, as shown by a significant correlation between the mean annual soil temperature and the minimum temperature for bacterial growth (T_min). Every 1 °C rise in soil temperature was estimated to increase T_min by 0.24–0.38 °C. The optimum temperature for bacterial growth varied less and did not have as clear a relationship with soil temperature. Temperature sensitivity, indicated by Q₁₀ values, increased with mean annual soil temperature, suggesting that bacterial communities from colder regions were less temperature sensitive than those from the warmer regions. The OTC warming (generally <1 °C temperature increases) over 3 years had no effects on temperature relationship of the soil bacterial community. We estimate that the predicted temperature increase of 2.6 °C for the Antarctic Peninsula would increase T_min by 0.6–1 °C and Q₁₀ (0–10 °C) by 0.5 units.