Nuclear phosphoinositides could bring FYVE alive

Phosphoinositide signalling systems exist in all eukaryotes. A high degree of evolutionary conservation is found at the functional level, but distinct phylogenetic differences are also becoming evident. Although the nuclear phosphoinositide system is likely to be a primordial forerunner of the plasma membrane system, relatively little is known about it. However, nuclear phosphoinositides might have far more diverse roles than hitherto envisaged and interact specifically with regulatory proteins containing phosphoinositide-binding domains. A novel family of proteins, so far only identified in plants, display domain structures that might link phosphoinositide metabolism to nuclear function in an unexpected way.     

Life history of harbor porpoises (Phocoena phocoena) in Scottish (UK) waters

Life history parameters were determined for stranded and bycaught harbor porpoises (Phocoena phocoena) from Scottish (UK) waters (1992–2005). Fetal growth rate was 84.4 mm/mo and mean size at birth was 76.4 cm (range 65–88 cm). Males and females had a similar range of body lengths (65–170 cm and 66–173 cm, respectively), although asymptotic lengths were higher in females than males (approximately 158 cm and 147 cm, respectively). Nonpregnant females were significantly lighter, in relation to their length than males. Maximum estimated age was 20 yr for both sexes. Age at sexual maturity (ASM) was estimated as 4.35 yr in females and 5.00 yr in males. Conception occurred mainly in July and August although reproductively active males were recorded during April to July. Gestation lasted 10–11 mo, with calving mainly between May and July. Lactating females were recorded during June to November, while small calves with solid food in their stomachs were found mainly during February to May. Estimated pregnancy rate (0.34–0.40) is lower than recorded elsewhere, but is likely underestimated due to the prevalence of mature females of poor health status in the sample. Nevertheless, cetacean strandings can be an essential source of data on demographic parameters.     

Bacillus subtilis RecA and its accessory factors,RecF, RecO,RecR and RecX,are required for spore resistance to DNA double-strand break

Bacillus subtilis RecA is important for spore resistance to DNA damage, even though spores contain a single non-replicating genome. We report that inactivation of RecA or its accessory factors, RecF, RecO, RecR and RecX, drastically reduce survival of mature dormant spores to ultrahigh vacuum desiccation and ionizing radiation that induce single strand (ss) DNA nicks and double-strand breaks (DSBs). The presence of non-cleavable LexA renders spores less sensitive to DSBs, and spores impaired in DSB recognition or end-processing show sensitivities to X-rays similar to wild-type. In vitro RecA cannot compete with SsbA for nucleation onto ssDNA in the presence of ATP. RecO is sufficient, at least in vitro, to overcome SsbA inhibition and stimulate RecA polymerization on SsbA-coated ssDNA. In the presence of SsbA, RecA slightly affects DNA replication in vitro, but addition of RecO facilitates RecA-mediated inhibition of DNA synthesis. We propose that repairing of the DNA lesions generates a replication stress to germinating spores, and the RecA·ssDNA filament might act by preventing potentially dangerous forms of DNA repair occurring during replication. RecA might stabilize a stalled fork or prevent or promote dissolution of reversed forks rather than its cleavage that should require end-processing.     

Osteoprotegerin CGA Haplotype Protection against Cerebrovascular Complications in Anti-CCP Negative Patients with Rheumatoid Arthritis

Introduction

Rheumatoid arthritis is an inflammatory disease with high incidence of cardiovascular disease due to accelerated atherosclerosis. Osteoprotegerin (OPG) has been associated with increased risk of atherosclerotic disease in the general population. Several polymorphisms in the OPG gene with functional effects on cardiovascular disease in non-rheumatic individuals have been described. Therefore, we aimed to analyze the effect of three of these functional OPG polymorphisms on the risk of cardiovascular disease in a large and well-characterized cohort of Spanish patients with rheumatoid arthritis.

Methods

Three OPG gene variants (rs3134063, rs2073618 and rs3134069) were genotyped by TaqMan assays in 2027 Spanish patients with rheumatoid arthritis. Anti-cyclic citrullinated peptide (anti-CCP) antibody testing was positive in 997 of 1714 tested. Also, 18.3% of the whole series had experienced cardiovascular events, including 5.4% with cerebrovascular accidents. The relationship between OPG variants and cardiovascular events was assessed using Cox regression.

Results

No association between OPG gene variants and cardiovascular disease was observed in the whole group of rheumatoid arthritis patients or in anti-CCP positive patients. Nevertheless, a protective effect of CGA haplotype on the risk of cardiovascular disease in general, and specifically in the risk of cerebrovascular complications after adjusting for sex, age at disease diagnosis and traditional cardiovascular risk factors was disclosed in anti-CCP negative patients (HR = 0.54; 95%CI: 0.31–0.95; p = 0.032 and HR = 0.17; 95%CI: 0.04–0.78; p = 0.022, respectively).

Conclusion

Our results indicate a protective effect of the OPG CGA haplotype on cardiovascular risk, mainly due to a protective effect against cerebrovascular events in anti-CCP negative rheumatoid arthritis patients.     

Genetic polymorphisms of CYP2C8, CYP2C9 and CYP2C19 in Ecuadorian Mestizo and Spaniard populations: a comparative study

This study was designed to investigate the potential differences between Spaniards and Ecuadorian Mestizo people regarding CYP2C8, CYP2C9, and CYP2C19 genetic polymorphisms. DNA from 282 Spaniard and 297 Ecuadorian subjects were analyzed by either a previously reported pyrosequencing method (CY2C8*3, CYP2C9*2, CYP2C9*3, CYP2C19*2 and CYP2C19*3) or a nested PCR technique (CYP2C19*17). Whereas CYP2C19*17 allele distribution was higher in Ecuadorians than in Spaniards (P < 0.001) and the frequency of CYP2C19*3 was similar in these two populations (P > 0.05), the other allelic variants were detected at significantly lower frequencies in Ecuadorians than in Spaniards (P < 0.05). According to the diplotype distributions, the prevalence of the presumed CYP2C9 and CYP2C8 extensive metabolizers was higher in Ecuadorians than in Spaniards (P < 0.05). Individuals genotyped CYP2C19*1/*17 and *17/*17 who were considered as ultrarapid metabolizers were overrepresented in Ecuadorians in relation to Spaniards (P < 0.001). By contrast, among Ecuadorians no poor metabolizers (PMs) of either CYP2C8 or CYP2C9 were found and only two individuals were CYP2C19 PMs. These data are compatible with a higher CYP2C8, CYP2C9, and CYP2C19 activity in Mestizo Ecuadorians as opposed to Spaniards, which could imply differences in dosage requirements for drugs metabolized by these cytochromes and should also be considered in allele-disease association studies.     

Indirect evidence of alteration in the expression of the rDNA genes in interspecific hybrids betweenDrosophila melanogaster andDrosophila simulans

Crosses betweenDrosophila melanogaster females andD. simulans males produce viable hybrid females, while males are lethal. These males are rescued if they carry theD. simulans Lhr gene. This paper reports that females of the wild-typeD. melanogaster population Staket do not produce viable hybrid males when crossed withD. simulans Lhr males, a phenomenon which we designate as the Staket phenotype. The agent responsible for this phenomenon was found to be the StaketX chromosome (X ^mel ,Stk). Analysis of the Staket phenotype showed that it is suppressed by extra copies ofD. melanogaster rDNA genes and that theX ^mel ,Stk chromosome manifests a weak bobbed phenotype inD. melanogaster X ^mel ,Stk/0 males. The numbers of functional rDNA genes inX ^mel ,Stk andX ^mel ,y w (control) chromosomes were found not to differ significantly. Thus a reduction in rDNA gene number cannot account for the weak bobbedX ^mel ,Stk phenotype let alone the Staket phenotype. The rRNA precursor molecules transcribed from theX ^mel ,Stk rDNA genes seem to be correctly processed in both intraspecific (melanogaster) and interspecific (melanogaster-simulans) conditions. It is therefore suggested that theX ^mel ,Stk rDNA genes are inefficiently transcribed in themelanogaster-simulans hybrids.