Myeloid deletion and therapeutic activation of AMPK do not alter atherosclerosis in male or female mice

The dysregulation of myeloid-derived cell metabolism can drive atherosclerosis. AMP-activated protein kinase (AMPK) controls various aspects of macrophage dynamics and lipid homeostasis, which are important during atherogenesis. Using LysM-Cre to drive the deletion of both the α1 and α2 catalytic subunits (MacKO), we aimed to clarify the role of myeloid-specific AMPK signaling in male and female mice made acutely atherosclerotic by injection of AAV vector encoding a gain-of-function mutant PCSK9 (PCSK9-AAV) and WD feeding. After 6 weeks of WD feeding, mice received a daily injection of either the AMPK activator A-769662 or a vehicle control for an additional 6 weeks. Following this (12 weeks total), we assessed myeloid cell populations and differences between genotype or sex were not observed. Similarly, aortic sinus plaque size, lipid staining, and necrotic area did not differ in male and female MacKO mice compared with their littermate floxed controls. Moreover, therapeutic intervention with A-769662 showed no treatment effect. There were also no observable differences in the amount of circulating total cholesterol or triglyceride, and only minor differences in the levels of inflammatory cytokines between groups. Finally, CD68+ area and markers of autophagy showed no effect of either lacking AMPK signaling or AMPK activation. Our data suggest that while defined roles for each catalytic AMPK subunit have been identified, complete deletion of myeloid AMPK signaling does not significantly impact atherosclerosis. Additionally, these findings suggest that intervention with the first-generation AMPK activator A-769662 is not able to stem the progression of atherosclerosis.     

Cks85A and Skp2 interact to maintain diploidy and promote growth in Drosophila

The Cks or Suc1 proteins are highly conserved small proteins that play remarkably diverse roles in the cell cycle. All Cks homologues have the ability to associate with Cyclin dependent kinases (Cdks) and in many cases this interaction has been shown to be important for function. Here we characterize the null and RNAi knockdown phenotype of the Drosophila Cks1 (Cks85A) gene. Cks85A is essential for viability in Drosophila. Cks85A null animals have reduced overall growth and this correlates with reduced ploidy and impaired DNA replication in endoreplicating cells. Interestingly, Cks85A is also required for the maintenance of diploidy in mitotically cycling cells. The requirement for Cks85A in growth is similar to that of the mammalian Cks1, which was found to interact with the SCF^Skp2 ubiquitin ligase. We identified the Drosophila Skp2 gene and generated null alleles. Comparison of these mutants to null mutants for Cks85A reveals a remarkably similar dual requirement in growth and in maintenance of diploidy. We find that Cks85A interacts directly with the SCF^Skp2 ubiquitin ligase and genetic evidence indicates that this is its major molecular function. The closely related Cks30A cannot interact with the SCF^Skp2 and cannot functionally compensate for loss of Cks85A. We also find that the critical growth promoting and diploidy maintaining functions of Cks85A and Skp2 are independent of known SCF^Skp2 substrates, p27 and Cdt1, indicating that other critical substrates remain to be identified.     

Molecular Mapping and Characterization of Genes Governing Time to Flowering, Seed Weight, and Plant Height in an Intraspecific Genetic Linkage Map of Chickpea (Cicer arietinum)

Drought is the major constraint to chickpea productivity worldwide. Utilizing early flowering genotypes and larger seed size have been suggested as strategies for breeding in drought zones. Therefore, this study aimed to identify potential markers linked to days-to-flowering, 100-seed weight, and plant height in a chickpea intraspecific F_2:3 population derived from the cross ILC3279 × ICCV2. A closely linked marker (TA117) on linkage group LG3 was identified for the days-to-flowering trait, explaining 33% of the variation. In relation to plant height, a quantitative trait loci (QTL) was located in LG3, close to the Ts5 marker, that explained 29% of phenotypic variation. A QTL for 100-seed weight located in LG4, close to TA176, explained 51% of variation. The identification of a locus linked both to high 100-seed weight and days-to-flowering may account for the correlation observed between these traits in this and other breeding attempts.     

Piriformospora indica inoculation alleviates the adverse effect of NaCl stress on growth,gas exchange and chlorophyll fluorescence in tomato (Solanum lycopersicum L.)

• Salinity is now an increasingly serious environmental issue that affects the growth and yield of many plants.
• In the present work, the influence of inoculation with the symbiotic fungus, Piriformospora indica, on gas exchange, water potential, osmolyte content, Na/K ratio and chlorophyll fluorescence of tomato plants under three salinity levels (0, 50, 100 and 150 mm NaCl) and three time periods (5, 10 and 15 days after exposure to salt) was investigated.
• Results indicate that P. indica inoculation improved growth parameters of tomato under salinity stress. This symbiotic fungus significantly increased photosynthetic pigment content under salinity, and more proline and glycine betaine accumulated in inoculated roots than in non‐inoculated roots. P. indica further significantly improved K⁺ content and reduced Na⁺ level under salinity treatment. After inoculation with the endophytic fungus, leaf physiological parameters, such as water potential, net photosynthesis, stomatal conductance and transpiration, were all higher under the salt concentrations and durations compared with controls without P. indica. With increasing salt level and salt treatment duration, values of F₀ and qP increased but F_m, F_v/F_m, F′_v/F′_m and NPQ declined in the controls, while inoculation with P. indica improved these values.
• The results indicate that the negative effects of NaCl on tomato plants were alleviated after P. indica inoculation, probably by improving physiological parameters such as water status and photosynthesis.

     

A Monte Carlo study on dose distribution evaluation of Flexisource 192Ir brachytherapy source

Aim

The aim of this study is to evaluate the dose distribution of the Flexisource ¹⁹²Ir source.

Background

Dosimetric evaluation of brachytherapy sources is recommended by task group number 43 (TG. 43) of American Association of Physicists in Medicine (AAPM).

Materials and methods

MCNPX code was used to simulate Flexisource ¹⁹²Ir source. Dose rate constant and radial dose function were obtained for water and soft tissue phantoms and compared with previous data on this source. Furthermore, dose rate along the transverse axis was obtained by simulation of the Flexisource and a point source and the obtained data were compared with those from Flexiplan treatment planning system (TPS).

Results

The values of dose rate constant obtained for water and soft tissue phantoms were equal to 1.108 and 1.106, respectively. The values of the radial dose function are listed in the form of tabulated data. The values of dose rate (cGy/s) obtained are shown in the form of tabulated data and figures. The maximum difference between TPS and Monte Carlo (MC) dose rate values was 11% in a water phantom at 6.0 cm from the source.

Conclusion

Based on dosimetric parameter comparisons with values previously published, the accuracy of our simulation of Flexisource ¹⁹²Ir was verified. The results of dose rate constant and radial dose function in water and soft tissue phantoms were the same for Flexisource and point sources. For Flexisource ¹⁹²Ir source, the results of TPS calculations in a water phantom were in agreement with the simulations within the calculation uncertainties. Furthermore, the results from the TPS calculation for Flexisource and MC calculation for a point source were practically equal within the calculation uncertainties.     

Temporal Responses of Propagule Banks during Ecological Restoration in the United Kingdom

Successful ecological restoration is expected to be accompanied by change in the propagule bank. We tested for temporal change in the soil propagule bank at two Bracken (Pteridium aquilinum)‐infested sites in the United Kingdom (acid grassland and heathland), each with replicate experiments. A combination of bracken control (cutting, spraying, and combinations) and vegetation restoration treatments (seeding, fertilizer, harrowing) were applied. Soil propagule banks were sampled in 1998, 4–5 years after the start, and in 2003 after a further 5 years. We used univariate and multivariate statistical methods to investigate the response of the propagule bank to experimental treatment in space and time. Few effects were found in 1998, but after a further 5 years, the propagule bank size and composition changed significantly, implying that propagule bank development lags behind vegetation development. The effect of treatment on the propagule bank differed within sites. Thus, ecosystem development is occurring at different speeds and directions even in closely adjacent areas. Coupling between the propagule bank and vegetation changed between sampling times with either some new coupling or decoupling. At both sites, the propagule bank contained propagules of the target community and thus propagule bank development during restoration provides increased potential for vegetation recovery. However, it can take a considerable time for management effects to be detected in the propagule bank. Moreover, the effect or speed of effect is spatially variable. Continuing application of restoration treatments is recommended at heathland where there is a deep bracken litter layer.