Treatment with apolipoprotein A-1 mimetic peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis

Introduction

The purpose of this study was to evaluate the effects of L-4F, an apolipoprotein A-1 mimetic peptide, alone or with pravastatin, in apoE^-/-Fas^-/-C57BL/6 mice that spontaneously develop immunoglobulin G (IgG) autoantibodies, glomerulonephritis, osteopenia, and atherosclerotic lesions on a normal chow diet.

Methods

Female mice, starting at eight to nine weeks of age, were treated for 27 weeks with 1) pravastatin, 2) L-4F, 3) L-4F plus pravastatin, or 4) vehicle control, followed by disease phenotype assessment.

Results

In preliminary studies, dysfunctional, proinflammatory high-density lipoproteins (piHDL) were decreased six hours after a single L-4F, but not scrambled L-4F, injection in eight- to nine-week old mice. After 35 weeks, L-4F-treated mice, in the absence/presence of pravastatin, had significantly smaller lymph nodes and glomerular tufts (P_{L, LP} < 0.05), lower serum levels of IgG antibodies to double stranded DNA (dsDNA) (P_L < 0.05) and oxidized phospholipids (oxPLs) (P_{L, LP} < 0.005), and elevated total and vertebral bone mineral density (P_{L, LP} < 0.01) compared to vehicle controls. Although all treatment groups presented larger aortic root lesions compared to vehicle controls, enlarged atheromas in combination treatment mice had significantly less infiltrated CD68⁺ macrophages (P_LP < 0.01), significantly increased mean α-actin stained area (P_LP < 0.05), and significantly lower levels of circulating markers for atherosclerosis progression, CCL19 (P_{L, LP} < 0.0005) and VCAM-1 (P_L < 0.0002).

Conclusions

L-4F treatment, alone or with pravastatin, significantly reduced IgG anti-dsDNA and IgG anti-oxPLs, proteinuria, glomerulonephritis, and osteopenia in a murine lupus model of accelerated atherosclerosis. Despite enlarged aortic lesions, increased smooth muscle content, decreased macrophage infiltration, and decreased pro-atherogenic chemokines in L-4F plus pravastatin treated mice suggest protective mechanisms not only on lupus-like disease, but also on potential plaque remodeling in a murine model of systemic lupus erythematosus (SLE) and accelerated atherosclerosis.     

Non-target effects of repeated methiocarb slug pellet application on carabid beetle (Coleoptera: Carabidae) activity in winter-sown cereals

The effects of repeated annual application of methiocarb-based slug pellets, broadcast on the soil surface and drilled into the seed bed, on carabid beetle activity were investigated over a four year period on a winter-sown cereal field using pitfall traps in barriered plots. Following applications in late autumn all winter-active carabid populations were severely depressed; total carabid activity falling to less than 5% and 10–15% following broadcast and drilled applications, respectively, compared with untreated plots. Spring and summer-active species, not active at the time of application, were largely unaffected by applications and were responsible for a gradual recovery of total activity from early spring onwards. Activity of all affected winter species remained demonstrably depressed on treated areas for the remainder of their seasonal incidence. However, all except one species, Bembidion obtusum, recovered to normal activity levels in the following season prior to reapplication. Recovery patterns are discussed in terms of the known biology of the species involved. Evidence that a minority of summer-active species were also affected by treatments, sometimes positively and sometimes negatively, were attributed to indirect effects possibly involving prey availability and foraging behaviour. The long-term ecological and short-term agronomic implications of methiocarb effects on carabid populations in winter-sown cereals are discussed.     

Anonymous nuclear DNA markers in the American oyster and their implications for the heterozygote deficiency phenomenon in marine bivalves

A puzzling population-genetic phenomenon widely reported in allozyme surveys of marine bivalves is the occurrence of heterozygote deficits relative to Hardy-Weinberg expectations. Possible explanations for this pattern are categorized with respect to whether the effects should be confined to protein-level assays or are genomically pervasive and expected to be registered in both protein- and DNA-level assays. Anonymous nuclear DNA markers from the American oyster were employed to reexamine the phenomenon. In assays based on the polymerase chain reaction (PCR), two DNA-level processes were encountered that can lead to artifactual genotypic scorings: (a) differential amplification of alleles at a target locus and (b) amplification from multiple paralogous loci. We describe symptoms of these complications and prescribe methods that should generally help to ameliorate them. When artifactual scorings at two anonymous DNA loci in the American oyster were corrected, Hardy-Weinberg deviations registered in preliminary population assays decreased to nonsignificant values. Implications of these findings for the heterozygote-deficit phenomenon in marine bivalves, and for the general development and use of PCR-based assays, are discussed.      

Brachiopod caeca – a respiratory role?

Recently the author presented data which supported the suggestion (Owen & Williams 1969) that the brachiopod caeca can inhibit boring organisms and store excess nutrients (Curry 1983). In the light of this work it is appropriate to describe and discuss an additional function which has been proposed for the caeca, especially as the data appear in a zoological journal which may not otherwise come to the attention of brachiopod palaeontologists.     

Monocarbonyl Analogs of Curcumin with Potential to Treat Colorectal Cancer

Curcumin has a plethora of biological properties, making this compound potentially effective in the treatment of several diseases, including cancer. However, curcumin clinical use is compromised by its poor pharmacokinetics, being crucial to find novel analogs with better pharmacokinetic and pharmacological properties. Here, we aimed to evaluate the stability, bioavailability and pharmacokinetic profiles of monocarbonyl analogs of curcumin. A small library of monocarbonyl analogs of curcumin 1a–q was synthesized. Lipophilicity and stability in physiological conditions were both assessed by HPLC-UV, while two different methods assessed the electrophilic character of each compound monitored by NMR and by UV-spectroscopy. The potential therapeutic effect of the analogs 1a–q was evaluated in human colon carcinoma cells and toxicity in immortalized hepatocytes. Our results showed that the curcumin analog 1e is a promising agent against colorectal cancer, with improved stability and efficacy/safety profile.     

Long‐term impacts of invasive species on a native top predator in a large lake system

1. Declining abundances of forage fish and the introduction and establishment of non‐indigenous species have the potential to substantially alter resource and habitat exploitation by top predators in large lakes. 2. We measured stable isotopes of carbon (δ¹³C) and nitrogen (δ¹⁵N) in field‐collected and archived samples of Lake Ontario lake trout (Salvelinus namaycush) and five species of prey fish and compared current trophic relationships of this top predator with historical samples. 3. Relationships between δ¹⁵N and lake trout age were temporally consistent throughout Lake Ontario and confirmed the role of lake trout as a top predator in this food web. However, δ¹³C values for age classes of lake trout collected in 2008 ranged from 1.0 to 3.9‰ higher than those reported for the population sampled in 1992. 4. Isotope mixing models predicted that these changes in resource assimilation were owing to the replacement of rainbow smelt (Osmerus mordax) by round goby (Neogobius melanostomus) in lake trout diet and increased reliance on carbon resources derived from nearshore production. This contrasts with the historical situation in Lake Ontario where δ¹³C values of the lake trout population were dominated by a reliance on offshore carbon production. 5. These results indicate a reduced capacity of the Lake Ontario offshore food web to support the energetic requirements of lake trout and that this top predator has become increasingly reliant on prey resources that are derived from nearshore carbon pathways.     

Urban Place: Reconnecting with the Natural World

Urban Place: Reconnecting with the Natural World. Peggy F. Barlett, ed. Cambridge, MA: MIT Press, 2005. 330 pp.     

Cheilostomatous Bryozoa from Vanuatu

The present account of some Bryozoa from Vanuatu is the first study of reef-flat species from the eastern Coral Sea. Based on samples collected from several shallow water localities on the island of Efate, a total of 92 species is described, including a new family, three new genera and 20 new species. Some of the newly recognized species are the result of taxonomic revision stimulated by these new samples, while others are entirely new to science. Of the new taxa described here, 16 are presently known only from Vanuatu. The total number of species recorded does not accurately represent the true taxonomic diversity of the Cheilostomatida of Vanuatu, and further sampling, at other localities and in other habitats, is needed before it can be reasonably estimated. The fauna is predominantly Indo-West Pacific in character with a high proportion of species apparently known only in the Southwest Pacific.     

Sampling properties of DNA sequence data in phylogenetic analysis

We inferred phylogenetic trees from individual genes and random samples of nucleotides from the mitochondrial genomes of 10 vertebrates and compared the results to those obtained by analyzing the whole genomes. Individual genes are poor samples in that they infrequently lead to the whole-genome tree. A large number of nucleotide sites is needed to exactly determine the whole-genome tree. A relatively small number of sites, however, often results in a tree close to the whole-genome tree. We found that blocks of contiguous sites were less likely to lead to the whole-genome tree than samples composed of sites drawn individually from throughout the genome. Samples of contiguous sites are not representative of the entire genome, a condition that violates a basic assumption of the bootstrap method as it is applied in phylogenetic studies.