In vivo dosimetry during DSA of the carotid and renal arteries. Deriviation of local DRLs

The Euratom directive 97/43 recommends the use of patient dose surveys in diagnostic radiology and the establishment of diagnostic reference dose levels (DRLs). The aims of this study are to perform measurements of the entrance surface dose (ESD) during diagnostic digital subtraction angiography (DSA) of the renal and carotid arteries using thermoluminescence dosemeters (TLDs), extraction of local DRLs, and calculation of the effective dose. Dose measurement for the staff was also performed. Dose measurements were performed on 48 participating patients. The mean effective dose was calculated to be 15.9 mSv and 8.9 mSv, for the renal and carotid DSA, respectively. The effective dose of the radiologist was calculated to be 0.022 mSv and 0.023 mSv per procedure for renal and carotid DSA respectively, when wearing a protective apron and using a movable ceiling mounted shield. Radiation dose variation depends on the physical characteristics of the patient, on the procedure preferences by radiologists and on the difficulties in conducting the procedures. The lack of DRLs for the specific examinations lead the research team to choose the DRL for DSA of the renal arteries to be 169 mGy for ESD at the pelvic region and for DSA of the carotid arteries to be 313 mGy for ESD at the region of the aortic arc.     

CCR5Delta32 protein expression and stability are critical for resistance to human immunodeficiency virus type 1 in vivo

Human immunodeficiency virus type 1 (HIV-1) infection of individuals carrying the two alleles of the CCR5Delta32 mutation (CCR5(-/-)) has rarely been reported, but how the virus overcomes the CCR5Delta32 protective effect in these cases has not been delineated. We have investigated this in 6 infected (HIV(+)) and 25 HIV(-) CCR5(-/-) individuals. CD4(+) T lymphocytes isolated from HIV(-) CCR5(-/-) peripheral blood mononuclear cells (PBMCs) showed lower levels of CXCR4 expression that correlated with lower X4 Env-mediated fusion. Endogenous CCR5Delta32 protein was detected in all HIV(-) CCR5(-/-) PBMC samples (n = 25) but not in four of six unrelated HIV(+) CCR5(-/-) PBMC samples. Low levels were detected in another two HIV(+) CCR5(-/-) PBMC samples. The expression of adenovirus 5 (Ad5)-encoded CCR5Delta32 protein restored the protective effect in PBMCs from three HIV(+) CCR5(-/-) individuals but failed to restore the protective effect in PBMCs isolated from another three HIV(+) CCR5(-/-) individuals. In the latter samples, pulse-chase analyses demonstrated the disappearance of endogenous Ad5-encoded CCR5Delta32 protein and the accumulation of Ad5-encoded CCR5 during the chase periods. PBMCs isolated from CCR5(-/-) individuals showed resistance to primary X4 but were readily infected by a lab-adapted X4 strain. Low levels of Ad5-encoded CCR5Delta32 protein conferred resistance to primary X4 but not to lab-adapted X4 virus. These data provide strong support for the hypothesis that the CCR5Delta32 protein actively confers resistance to HIV-1 in vivo and suggest that the loss or reduction of CCR5Delta32 protein expression may account for HIV-1 infection of CCR5(-/-) individuals. The results also suggest that other cellular or virally induced factors may be involved in the stability of CCR5Delta32 protein.     

Spermidine triggering effect to the signal transduction through the AtoS-AtoC/Az two-component system in Escherichia coli

Recent analysis revealed that, in Escherichia coli the AtoS-AtoC/Az two-component system (TCS) and its target atoDAEB operon regulate the biosynthesis of short-chain poly-(R)-3-hydroxybutyrate (cPHB) biosynthesis, a biopolymer with many physiological roles, upon acetoacetate-mediated induction. We report here that spermidine further enhanced this effect, in E. coli that overproduces both components of the AtoS-AtoC/Az TCS, without altering their protein levels. However, bacteria that overproduce either AtoS or AtoC did not display this phenotype. The extrachromosomal introduction of AtoS-AtoC/Az in an E. coli DeltaatoSC strain restored cPHB biosynthesis to the level of the atoSC(+) cells, in the presence of the polyamine. Lack of enhanced cPHB production was observed in cells overproducing the TCS that did not have the atoDAEB operon. Spermidine attained the cPHB enhancement through the AtoC/Az response regulator phosphorylation, since atoC phosphorylation site mutants, which overproduce AtoS, accumulated less amounts of cPHB, compared to their wild-type counterparts. Exogenous addition of N(8)-acetyl-spermidine resulted in elevated amounts of cPHB but at lower levels than those attained upon spermidine addition. Furthermore, AtoS-AtoC/Az altered the intracellular distribution of cPHB according to the inducer recognized by the TCS. Overall, AtoS-AtoC/Az TCS was induced by spermidine to regulate both the biosynthesis and the intracellular distribution of cPHB in E. coli.     

The population genetics of two orchid bees suggests high dispersal,low diploid male production and only an effect of island isolation in lowering genetic diversity

Orchid bees (Hymenoptera, Apidae, Euglossini) are important pollinators of many plant families in Neotropical forests, habitats that have become increasingly degraded and fragmented by agricultural practices. To understand the extent to which loss of natural habitat and isolation has affected the genetic diversity and diploid male production (DMP) of two orchid bee species, Euglossa dilemma and Euglossa viridissima, we collected and genotyped 1686 males at five microsatellite loci and tested for differences in allelic richness, heterozygosity and DMP across three different types of land use (natural, agricultural and urban) and between mainland and island populations in the Yucatan Peninsula of Mexico. We also investigated the impact of land use and geographic isolation on gene flow. Euglossa dilemma and E. viridissima seemed to be particularly resilient to loss of natural habitat; in locations with human impact, we did not find reduced genetic diversity, and populations generally showed very little population genetic structure. Only on islands did E. dilemma show significantly reduced genetic diversity. Even after accounting for putative null alleles, DMP was very low (0.2–1.3%) across all sampling sites, including on islands. We therefore suggest that DMP is an insensitive measure of inbreeding and population decline in our two study species.     

Inbreeding depression and drift load in small populations at demographic disequilibrium

Inbreeding depression is a major driver of mating system evolution and has critical implications for population viability. Theoretical and empirical attention has been paid to predicting how inbreeding depression varies with population size. Lower inbreeding depression is predicted in small populations at equilibrium, primarily due to higher inbreeding rates facilitating purging and/or fixation of deleterious alleles (drift load), but predictions at demographic and genetic disequilibrium are less clear. In this study, we experimentally evaluate how lifetime inbreeding depression and drift load, estimated by heterosis, vary with census (N_c) and effective (estimated as genetic diversity, H_e) population size across six populations of the biennial Sabatia angularis as well as present novel models of inbreeding depression and heterosis under varying demographic scenarios at disequilibrium (fragmentation, bottlenecks, disturbances). Our experimental study reveals high average inbreeding depression and heterosis across populations. Across our small sample, heterosis declined with H_e, as predicted, whereas inbreeding depression did not vary with H_e and actually decreased with N_c. Our theoretical results demonstrate that inbreeding depression and heterosis levels can vary widely across populations at disequilibrium despite similar H_e and highlight that joint demographic and genetic dynamics are key to predicting patterns of genetic load in nonequilibrium systems.