Association study of three polymorphisms of the TGF-β1 gene with AD

Objectives: To explore the impact of the -800 and -509 TGF-ß1 promoter polymorphisms and the +25 polymorphism on the risk of occurrence of Alzheimer's disease in a large population of sporadic cases and controls, and on the amyloid ß (Aß) load in the brains of Alzheimer patients. Methods: The TGF-ß1 genotypes of the three polymorphisms were determined in 678 sporadic Alzheimer's disease patients and 667 controls. They were also characterised, along with Aß load, in the brains of 81 necropsy confirmed Alzheimer patients. Results: No significant variations in the distribution of the genotypes and haplotypes were observed between Alzheimer patients and controls, or in the amount of Aß deposition. Conclusions: These results do not suggest an influence of genetic variability at the TGF-ß1 gene locus on the occurrence of Alzheimer's disease

A plantar flexion device exercise programme for patients with peripheral arterial disease: a randomised prospective feasibility study

Objectives: To determine if the use of a plantar flexion device (Step It pedal) in a newly developed exercise programme is of benefit to patients with peripheral arterial disease. Design: Prospective feasibility trial with patients randomised to either standard care or the Step It exercise programme plus standard care. Setting: Physiotherapy Department at Cumberland Infirmary, Carlisle, UK. Participants: Patients were identified from the vascular team's referral list. In total, 42 patients agreed to take part; 18 in the control group and 24 in the intervention group. Interventions: Eligible participants were randomised and received either standard care or took part in a plantar flexion resistance exercise programme, involving the Step It pedal, for a period of 12 weeks. Main outcome measures: Maximum walking distance, claudication distance and ankle brachial pressure index. Results: Eighty-three percent of patients completed the study. Improvements in median distance to claudication symptoms and maximum walking distance were observed in the intervention group but not in the control group. Nine out of 15 (60%) participants in the control group and 14 out of 20 (70%) participants in the intervention group improved their walking distance. Ankle brachial pressure index remained virtually unchanged in both groups. Conclusions: Due to the variability of patients' fitness in the sample, it cannot be concluded whether use of the Step It pedal has additional benefits to patients over standard care. However, the study completion rate implies that patients with peripheral arterial disease are receptive to undertaking exercise programmes

Live-bearing cockroach genome reveals convergent evolutionary mechanisms linked to viviparity in insects and beyond

Live birth (viviparity) has arisen repeatedly and independently among animals. We sequenced the genome and transcriptome of the viviparous Pacific beetle-mimic cockroach and performed comparative analyses with two other viviparous insect lineages, tsetse flies and aphids, to unravel the basis underlying the transition to viviparity in insects. We identified pathways undergoing adaptive evolution for insects, involved in urogenital remodeling, tracheal system, heart development, and nutrient metabolism. Transcriptomic analysis of cockroach and tsetse flies revealed that uterine remodeling and nutrient production are increased and the immune response is altered during pregnancy, facilitating structural and physiological changes to accommodate and nourish the progeny. These patterns of convergent evolution of viviparity among insects, together with similar adaptive mechanisms identified among vertebrates, highlight that the transition to viviparity requires changes in urogenital remodeling, enhanced tracheal and heart development (corresponding to angiogenesis in vertebrates), altered nutrient metabolism, and shifted immunity in animal systems.</p

Association of 3'-UTR polymorphisms of the oxidised LDL receptor 1 (OLR1) gene with Alzheimer's disease

Although possession of the ε4 allele of the apolipoprotein E gene appears to be an important biological marker for Alzheimer's disease (AD) susceptibility, strong evidence indicates that at least one additional risk gene exists on chromosome 12. Here, we describe an association of the 3'-UTR +1073 C/T polymorphism of the OLR1 (oxidised LDL receptor 1) on chromosome 12 with AD in French sporadic (589 cases and 663 controls) and American familial (230 affected sibs and 143 unaffected sibs) populations. The age and sex adjusted odds ratio between the CC+CT genotypes versus the TT genotypes was 1.56 (p=0.001) in the French sample and 1.92 (p=0.02) in the American sample. Furthermore, we have discovered a new T/A polymorphism two bases upstream of the +1073 C/T polymorphism. This +1071 T/A polymorphism was not associated with the disease, although it may weakly modulate the impact of the +1073 C/T polymorphism. Using 3'-UTR sequence probes, we have observed specific DNA protein binding with nuclear proteins from lymphocyte, astrocytoma, and neuroblastoma cell lines, but not from the microglia cell line. This binding was modified by both the +1071 T/A and +1073 C/T polymorphisms. In addition, a trend was observed between the presence or absence of the +1073 C allele and the level of astrocytic activation in the brain of AD cases. However, Aß(40), Aß(42), Aß total, and Tau loads or the level of microglial cell activation were not modulated by the 3'-UTR OLR1 polymorphisms. Finally, we assessed the impact of these polymorphisms on the level of OLR1 expression in lymphocytes from AD cases compared with controls. The OLR1 expression was significantly lower in AD cases bearing the CC and CT genotypes compared with controls with the same genotypes. In conclusion, our data suggest that genetic variation in the OLR1 gene may modify the risk of AD