Inhibited aortic aneurysm formation in BLT1-deficient mice

Leukotriene B(4) is a proinflammatory lipid mediator generated by the enzymes 5-lipoxygenase and leukotriene A(4) hydrolase. Leukotriene B(4) signals primarily through its high-affinity G protein-coupled receptor, BLT1, which is highly expressed on specific leukocyte subsets. Recent genetic studies in humans as well as knockout studies in mice have implicated the leukotriene synthesis pathway in several vascular pathologies. In this study, we tested the hypothesis that BLT1 is necessary for abdominal aortic aneurysm (AAA) formation, a major complication of atherosclerotic vascular disease. Chow-fed Apoe(-/-) and Apoe(-/-)/Blt1(-/-) mice were treated with a 4-wk infusion of angiotensin II (1000 ng/min/kg) beginning at 20 wk of age, in a well-established murine AAA model. We found a reduced incidence of AAA formation as well as concordant reductions in the maximum suprarenal/infrarenal diameter and total suprarenal/infrarenal area in the angiotensin II-treated Apoe(-/-)/Blt1(-/-) mice as compared with the Apoe(-/-) controls. Diminished AAA formation in BLT1-deficient mice was associated with significant reductions in mononuclear cell chemoattractants and leukocyte accumulation in the vessel wall, as well as striking reductions in the production of matrix metalloproteinases-2 and -9. Thus, we have shown that BLT1 contributes to the frequency and size of abdominal aortic aneurysms in mice and that BLT1 deletion in turn inhibits proinflammatory circuits and enzymes that modulate vessel wall integrity. These findings extend the role of BLT1 to a critical complication of vascular disease and underscore its potential as a target for intervention in modulating multiple pathologies related to atherosclerosis.     

Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1 polymorphisms

Background

Animal studies suggest that brain apolipoprotein E (apoE) levels influence amyloid-β (Aβ) deposition and thus risk for Alzheimer's disease (AD). We have previously demonstrated that deletion of the ATP-binding cassette A1 transporter (ABCA1) in mice causes dramatic reductions in brain and cerebrospinal fluid (CSF) apoE levels and lipidation. To examine whether polymorphisms in ABCA1 affect CSF apoE levels in humans, we measured apoE in CSF taken from 168 subjects who were 43 to 91 years old and were either cognitively normal or who had mild AD. We then genotyped the subjects for ten previously identified ABCA1 single nucleotide polymorphisms (SNPs).

Results

In all subjects, the mean CSF apoE level was 9.09 μg/ml with a standard deviation of 2.70 μg/ml. Levels of apoE in CSF samples taken from the same individual two weeks apart were strongly correlated (r² = 0.93, p < 0.01). In contrast, CSF apoE levels in different individuals varied widely (coefficient of variation = 46%). CSF apoE levels did not vary according to AD status, APOE genotype, gender or race. Average apoE levels increased with age by ~0.5 μg/ml per 10 years (r² = 0.05, p = 0.003). We found no significant associations between CSF apoE levels and the ten ABCA1 SNPs we genotyped. Moreover, in a separate sample of 1225 AD cases and 1431 controls, we found no association between the ABCA1 SNP rs2230806 and AD as has been previously reported.

Conclusion

We found that CSF apoE levels vary widely between individuals, but are stable within individuals over a two-week interval. AD status, APOE genotype, gender and race do not affect CSF apoE levels, but average CSF apoE levels increase with age. Given the lack of association between CSF apoE levels and genotypes for the ABCA1 SNPs we examined, either these SNPs do not affect ABCA1 function or if they do, they do not have strong effects in the CNS. Finally, we find no evidence for an association between the ABCA1 SNP rs2230806 and AD in a large sample set.     

Generalized spectral light scatter models of diverse bacterial colony morphologies

An optical forward‐scatter model was generalized to encompass the diverse nature of bacterial colony morphologies and the spectral information. According to the model, the colony shape and the wavelength of incident light significantly affect the characteristics of a forward elastic‐light‐scattering pattern. To study the relationship between the colony morphology and the scattering pattern, three‐dimensional colony models were generated in various morphologies. The propagation of light passing through the colony model was then simulated. In validation of the theoretical modeling, the scattering patterns of three bacterial genera, Staphylococcus, Exiguobacterium and Bacillus, which grow into colonies having convex, crateriform and flat elevations, respectively, were qualitatively compared to the simulated scattering patterns. The strong correlations observed between simulated and experimental patterns validated the scatter model. In addition, spectral effect on the scattering pattern was studied using the scatter model, and experimentally investigated using Staphylococcus, whose colony has circular form and convex elevation. Both simulation and experiment showed that changes in wavelength affected the overall pattern size and the number of rings.     

Systematics of the Madagascar Anelosimus spiders: remarkable local richness and endemism,and dual colonization from the Americas

Despite the alarming rates of deforestation and forest fragmentation, Madagascar still harbors extraordinary biodiversity. However, in many arthropod groups, such as spiders, this biodiversity remains mostly unexplored and undescribed. The first subsocial Madagascan species of the theridiid spider genus Anelosimus were described in 2005 when six new species were found to coexist in the Périnet forest fragment within Andasibe-Mantadia NP. However, this discovery was based only on a few specimens and the extent of this Madagascan radiation has remained unknown. We here report on a thorough survey of >350 colonies from Périnet, and three pilot surveys into additional Madagascar forests (Ambohitantely, Ranamofana, and Montagne d’Ambre). The morphological, molecular and natural history data from these surveys facilitated a revised taxonomy and phylogenetic hypothesis of Madagascan Anelosimus. This subsocial clade currently comprises six previously known (Anelosimus andasibe Agnarsson & Kuntner, 2005, Anelosimus may Agnarsson, 2005, Anelosimus nazariani Agnarsson & Kuntner, 2005, Anelosimus sallee Agnarsson & Kuntner, 2005, Anelosimus salut Agnarsson & Kuntner, 2005, Anelosimus vondrona Agnarsson & Kuntner, 2005) and 10 new species: Anelosimus ata sp. n., Anelosimus buffoni sp. n., Anelosimus darwini sp. n., Anelosimus hookeri sp. n., Anelosimus huxleyi sp. n., Anelosimus lamarcki sp. n., Anelosimus moramora sp. n., Anelosimus tita sp. n., Anelosimus torfi sp. n., Anelosimus wallacei sp. n.. With the exception of Anelosimus may and Anelosimus vondrona, all other species appear to be single forest endemics. While additional sampling is necessary, these data imply a much higher local richness and endemism in Madagascan forests than in any other comparable area globally. The phylogenetic results establish a sister clade relationship between the subsocial Anelosimus in Madagascar and the American ‘eximius group’, and between the solitary Anelosimus decaryi on Madagascar and a solitary American clade. These findings imply duplicate colonizations from America, an otherwise rare biogeographical pattern, calling for more detailed investigation of Anelosimus biogeography.     

Similar patterns of frequency‐dependent selection on animal personalities emerge in three species of social spiders

Frequency‐dependent selection is thought to be a major contributor to the maintenance of phenotypic variation. We tested for frequency‐dependent selection on contrasting behavioural strategies, termed here ‘personalities’, in three species of social spiders, each thought to represent an independent evolutionary origin of sociality. The evolution of sociality in the spider genus Anelosimus is consistently met with the emergence of two temporally stable discrete personality types: an ‘aggressive’ or ‘docile’ form. We assessed how the foraging success of each phenotype changes as a function of its representation within a colony. We did this by creating experimental colonies of various compositions (six aggressives, three aggressives and three dociles, one aggressive and five dociles, six dociles), maintaining them in a common garden for 3 weeks, and tracking the mass gained by individuals of either phenotype. We found that both the docile and aggressive phenotypes experienced their greatest mass gain in mixed colonies of mostly docile individuals. However, the performance of both phenotypes decreased as the frequency of the aggressive phenotype increased. Nearly identical patterns of phenotype‐specific frequency dependence were recovered in all three species. Naturally occurring colonies of these spiders exhibit mixtures dominated by the docile phenotype, suggesting that these spiders may have evolved mechanisms to maintain the compositions that maximize the success of the colony without compromising the expected reproductive output of either phenotype.     

A study to determine the impact of IMPT optimization techniques on prostate synthetic CT image sets dose comparison against CT image sets

BackgroundThe objective of this study is to determine the impact of intensity modulated proton therapty (IMPT) optimization techniques on the proton dose comparison of commercially available magnetic resonance for calculating attenuation (MRCA T) images, a synthetic computed tomography CT (sCT) based on magnetic resonance imaging (MRI) scan against the CT images and find out the optimization technique which creates plans with the least dose differences against the regular CT image sets.Material and methodsRegular CT data sets and sCT image sets were obtained for 10 prostate patients for the study. Six plans were created using six distinct IMPT optimization techniques including multi-field optimization (MFO), single field uniform dose (SFUD) optimization, and robust optimization (RO) in CT image sets. These plans were copied to MRCA T, sCT datasets and doses were computed. Doses from CT and MRCA T data sets were compared for each patient using 2D dose distribution display, dose volume histograms (DVH), homogeneity index (HI), conformation number (CN) and 3D gamma analysis. A two tailed t-test was conducted on HI and CN with 5% significance level with a null hypothesis for CT and sCT image sets.ResultsAnalysis of ten CT and sCT image sets with different IMPT optimization techniques shows that a few of the techniques show significant differences between plans for a few evaluation parameters. Isodose lines, DVH, HI, CN and t-test analysis shows that robust optimizations with 2% range error incorporated results in plans, when re-computed in sCT image sets results in the least dose differences against CT plans compared to other optimization techniques. The second best optimization technique with the least dose differences was robust optimization with 5% range error.ConclusionThis study affirmatively demonstrates the impact of IMPT optimization techniques on synthetic CT image sets dose comparison against CT images and determines the robust optimization with 2% range error as the optimization technique which gives the least dose difference when compared to CT plans.