Constraint and competition in assemblages: a cross-continental and modeling approach for ants

The mechanisms leading to structure in local assemblages are controversial. On the one hand, assemblage structure is thought to be the outcome of local interactions determined by the properties of species and their responses to the local environment. Alternatively, this structure has been shown to be an emergent property of assemblages of identical individuals or of random sampling of a regional assemblage. In ants at baits, a combination of environmental stress and interspecific competition is widely held to lead to a unimodal relationship between the abundance of dominant ants and species richness. It is thought that in comparatively adverse environments, both abundance and richness are low. As habitats become more favorable, abundance increases until the abundance of dominant ants is so high that they exclude those that are subordinate and so depress richness. Here we demonstrate empirically that this relationship is remarkably similar across three continents. Using a null model approach, we then show that the ascending part of the relationship is largely constrained to take this form not simply as a consequence of stress but also as a result of the shape of abundance frequency distributions. While the form of the species-abundance frequency distribution can also produce the descending part of the relationship, interspecific competition might lead to it too. Scatter about the relationship, which is generally not discussed in the literature, may well be a consequence of resource availability and environmental patchiness. Our results draw attention to the significance of regional processes in structuring ant assemblages.     

Proposed reference dose for toxaphene carcinogenicity based on constitutive androstane receptor-mediated mode of action

Toxaphene is a liver tumor promoter in B6C3F1 mice but not in F344 rats or hamsters. Recent studies demonstrate that key events leading to the mouse liver tumor response for toxaphene are mediated by activation of the constitutive androstane receptor (CAR). Benchmark dose modeling was conducted on available data for five endpoints in B6C3F1 mouse liver tissue or cultured liver cells (tumor response, cytotoxicity, proliferation, gap junction intercellular communication inhibition, and CAR-mediated CYP2B10 induction) and for CAR activation in human HepG2 cells, all reported in previous studies. The available evidence supports a nonlinear CAR-mediated mode of action (MOA) for toxaphene-induced mouse tumors including demonstration of a J-shaped dose-response pattern for human CAR activation, indicating that linear risk extrapolation at low doses is not supported for this MOA. Based on analysis of benchmark dose lower confidence limits at 10% response (BMDL10) and no observed effect levels (NOELs) for potential key events in the mouse liver tumor MOA for toxaphene, an RfD of 0.13 mg/kg-d is proposed based on a the BMDL10 for human CAR activation in human HepG2 cells. This value is below candidate RfD values based on BMDL10 estimates for both mouse liver tumors and mouse hepatocyte proliferation and therefore can be considered protective for human risk of liver tumor promotion and other CAR-mediated adverse health effects based on available data.     

Using three-point bending to evaluate tibia bone strength in ovariectomized young mice

It is well known that estrogen deficiency induces a deterioration of bone strength in aged females. The aim of this study is to determine the effect of estrogen depletion on tibia bone strength in sexually mature mice that are still undergoing skeletal maturation. At 8 weeks of age, C57BL/6 female mice underwent an ovariectomy (OVX) or sham (SHAM) surgery. Mice were killed at 2, 4, or 8 weeks post-surgery. Tibia length and cross-sectional area continued to increase in both treatment groups until 4 weeks post-surgery. Compared to SHAM mice, OVX mice demonstrated a significant reduction in uterine weight and plasma estrogen levels. Three-point bending was used to quantify the mechanical properties (breaking point, stress, stiffness, and elasticity) of the tibia. The tibias from the SHAM mice had a higher breaking point than all the age-matched OVX mice. At 8 weeks post-surgery, the tibias from the SHAM mice demonstrated higher elasticity, stress, and stiffness than the younger SHAM mice and the age-matched OVX mice. Compared to the SHAM mice, our study suggests that (1) there is a reduction in the mechanical strength of tibias from young OVX mice, and (2) the greatest decline in tibia strength of the OVX mice was once they reached skeletal maturity.     

Protein Phosphorylation and Calcium Uptake into Rat Forebrain Synaptosomes: Modulation by the σ Ligand, 1,3-Ditolylguanidine

Abstract: The σ ligand 1,3-di- O -tolylguanidine (DTG) increased basal dynamin and decreased depolarization-stimulated phosphorylation of the synaptosomal protein synapsin Ib without having direct effects on protein kinases or protein phosphatases. DTG dose-dependently decreased the basal cytosolic free Ca²⁺ concentration ([Ca²⁺]_i) and blocked the depolarization-dependent increases in [Ca²⁺]_i. These effects were inhibited by the σ antagonists rimcazole and BMY14802. The nitric oxide donors sodium nitroprusside (SNP) and 8-( p -chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate decreased basal [Ca²⁺]_i and the KCl-evoked rise in [Ca²⁺]_i to an extent similar to DTG. SNP, but not DTG, produced a rise in cyclic GMP levels, suggesting that the effect of DTG on [Ca²⁺]_i was not mediated via downstream regulation of cyclic GMP levels. DTG increased ⁴⁵Ca²⁺ uptake and efflux under basal conditions and inhibited the ⁴⁵Ca²⁺ uptake induced by depolarization with KCl. The KCl-evoked rise in [Ca²⁺]_i was inhibited by ω-conotoxin (ω-CgTx)-GVIA and -MVIIC but not nifedipine and ω-agatoxin-IVA. The effect of DTG on decreasing the KCl-evoked rise in [Ca²⁺]_i was additive with ω-CgTx-MVIIC but not with ω-CgTx-GVIA. These data suggest that DTG was producing some of its effects on synapsin I and dynamin phosphorylation and intrasynaptosomal Ca²⁺ levels via inhibition of N-type Ca²⁺ channels.     

Geographic variation in cardiovascular inflammation among healthy women in the Women's Health Study

Background

Geographic variation in traditional cardiovascular disease (CVD) risk factors has been observed among women in the US. It is not known whether state-level variation in cardiovascular inflammation exists or could be explained by traditional clinical risk factors and behavioral lifestyle factors.

Methods and Results

We used multilevel linear regression to estimate state-level variation in inflammatory biomarker patterns adjusted for clinical and lifestyle characteristics among 26,029 women free of CVD. Participants derived from the Women''s Health Study, a national cohort of healthy middle-aged and older women. Inflammatory biomarker patterns (plasma levels of high-sensitivity C-reactive protein (hsCRP), soluble intercellular adhesion molecule-1 (sICAM-1), and fibrinogen) were compared to state-level patterns of traditional CVD risk factors and global risk scores. We found that all three inflammatory biomarkers exhibited significant state-level variation including hsCRP (lowest vs. highest state median 1.3 mg/L vs. 2.7 mg/L, unadjusted random effect estimate 1^st to 99^th percentile range for log hsCRP 0.52, p<.001), sICAM-1 (325 ng/ml vs. 366ng/ml, unadjusted random effect estimate 1^st to 99^th percentile range 0.44, p<.001), and fibrinogen (322 mg/dL vs. 367 mg/dL, unadjusted random effect estimate 1^st to 99^th percentile range 0.41, p = .001). Neither demographic, clinical or lifestyle characteristics explained away state-level effects in biomarker patterns. Southern and Appalachian states (Arkansas, West Virginia) had the highest inflammatory biomarker values. Regional geographic patterns of traditional CVD risk factors and risk scores did not completely overlap with biomarkers of inflammation.

Conclusions

There is state-level geographic variation in inflammatory biomarkers among otherwise healthy women that cannot be completely attributed to traditional clinical risk factors or lifestyle characteristics. Future research should aim to identify additional factors that may explain geographic variation in biomarkers of inflammation among healthy women.     

Adenovirus-5-vectored P. falciparum vaccine expressing CSP and AMA1. Part B: safety, immunogenicity and protective efficacy of the CSP component

Background

A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.

Methodology/Principal Findings

NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.

Significance

The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00392015","term_id":"NCT00392015"}}NCT00392015     

Rapid Schedules for Koh Clearing and Alizarin Red S Staining of Fetal Rat Bone

Various schedules for staining fetal rat skeleton with alizarin red S were tested to determine a procedure that would produce a completely cleared and well-stained specimen in a short period of time. A 2 day procedure is presented which can produce specimens that are satisfactory but not completely transparent. A 7 day procedure produces cleared and stained specimens which can be well visualized with a dissecting microscope (30×). Fetal rats of 21 days gestation were fixed in 10% formalin for at least 1 wk. The specimens were skinned and eviscerated and then dehydrated in 2 changes of acetone for 12 hr (8 ml per gram body weight). The specimens were then placed in 1% KOM-alizarin red S (6 mg/liter) or 3 days, followed by 10% KOH-alizarin red S for 3 days. Finally, the specimens were placed in a mixture of benzyl alcohol, ethanol, and glycerol (1:2:2) (4 ml per gram body weight) for 12 hr, and then transferred to pure glycerol for storage.