Intrauterine programming of ageing

Ageing is an unavoidable corollary to being alive; the most intuitive interpretation of ageing being that it is the consequence of progressive body degeneration. In agreement with this, current models propose that ageing occurs through a stepwise accumulation of DNA damage, which ultimately limits the regenerative capacity of tissues. On the other hand, there is increasing evidence that fetal distress can influence the development of disease in adult life, a phenomenon known as ‘intrauterine programming’. The extent to which an intrauterine exposure to DNA damage can compromise lifespan remains unclear. My group has recently generated a murine model of a human syndrome linked to defective DNA repair and observed that these animals age prematurely, but the accumulation of DNA damage is restricted mostly to the embryonic period. Here, I discuss the implications of this finding and propose that ageing can be influenced by fetal distress.     

Functional Effects of Adiponectin on Endothelial Progenitor Cells

Adiponectin is an adipokine whose plasma levels are inversely correlated to metabolic syndrome components. Adiponectin protects against atherosclerosis and decreases risks in myocardial infarction. Endothelial progenitor cells (EPCs) are a heterogeneous population of circulating cells involved in vascular repair and neovascularization. EPCs number is reduced in patients with cardiovascular disease. We hypothesize that the positive effects of adiponectin against atherosclerosis are explained in part by its interactions with EPCs. Cells were obtained from healthy volunteers' blood by mononuclear cell isolation and plating on collagen‐coated dishes. Three sub‐populations of EPCs were identified and characterized using flow cytometry. EPCs' expression of adiponectin receptors, AdipoR1, and AdipoR2 was evaluated by quantitative PCR. The effects of recombinant adiponectin on EPCs' susceptibility to apoptosis were assessed. Finally, expression of neutrophil elastase by EPCs and activity of this enzyme on adiponectin processing were assessed. Quantitative PCR analysis of EPCs mRNAs showed that AdipoR1 mRNA is expressed at higher levels than AdipoR2. Expression of AdipoR1 protein was confirmed by western blot. Adiponectin significantly increased survival of two sub‐populations of EPCs in conditions of serum deprivation. Such effect could not be demonstrated in the third EPCs sub‐population. We also demonstrated that EPCs, particularly one sub‐population, express neutrophil elastase. Neutrophil elastase activity was confirmed in EPCs' conditioned media. Adiponectin protects some EPCs sub‐populations against apoptosis and therefore could modulate EPCs ability to induce repair of vascular damage. Neutrophil elastase activity of EPCs could locally modulate adiponectin activity by its involvement in the generation of the globular form of adiponectin.     

On the classification of Calligonum juochiangense and C. pumilum (Polygonaceae)

After observing specimens of Calligonum pumilum Losinsk. and C. juochiangense Y. X. Liou in both the field and in herbarium collections, it was found that the morphological characters of these two species are quite different, especially with respect of the twisted direction of fruit ribs, number of bristle rows along each rib, rigidity and degree of interweaving of bristles, as well as their geographic distribution. Therefore, it is concluded that C. pumilum and C. juochiangense should be accepted as two independent species.     

Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer’s disease

Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer’s disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure–activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid β-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC₅₀?=?10.2?±?1.2, 16.5?±?1.7, and 15.3?±?1.8?nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD.     

Prenatal diagnosis of Pallister-Killian syndrome and literature review

Pallister-Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2−4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS.     

Farms,pastures and woodlands: the fine‐scale distribution of Palearctic Culicoides spp. biting midges along an agro‐ecological gradient

The spatial epidemiology of Bluetongue virus (BTV) at the landscape level relates to the fine‐scale distribution and dispersal capacities of its vectors, midges belonging to the genus Culicoides Latreille (Diptera: Ceratopogonidae). Although many previous researches have carried out Culicoides sampling on farms, little is known of the fine‐scale distribution of Culicoides in the landscape immediately surrounding farms. The aim of this study was to gain a better understanding of Culicoides populations at increasing distances from typical dairy farms in north‐west Europe, through the use of eight Onderstepoort‐type black‐light traps positioned along linear transects departing from farms, going through pastures and entering woodlands. A total of 16 902 Culicoides were collected in autumn 2008 and spring 2009. The majority were females, of which more than 97% were recognized as potential vectors. In pastures, we found decreasing numbers of female Culicoides as a function of the distance to the farm. This pattern was modelled by leptokurtic models, with parameters depending on season and species. By contrast, the low number of male Culicoides caught were homogeneously distributed along the transects. When transects entered woodlands, we found a higher abundance of Culicoides than expected considering the distance of the sampling sites to the farm, although this varied according to species.     

Functional RelBE-Family Toxin-Antitoxin Pairs Affect Biofilm Maturation and Intestine Colonization in Vibrio cholerae

Toxin–antitoxin (TA) systems are small genetic elements that typically encode a stable toxin and its labile antitoxin. These cognate pairs are abundant in prokaryotes and have been shown to regulate various cellular functions. Vibrio cholerae, a human pathogen that is the causative agent of cholera, harbors at least thirteen TA loci. While functional HigBA, ParDE have been shown to stabilize plasmids and Phd/Doc to mediate cell death in V. cholerae, the function of seven RelBE-family TA systems is not understood. In this study we investigated the function of the RelBE TA systems in V. cholerae physiology and found that six of the seven relBE loci encoded functional toxins in E. coli. Deletion analyses of each relBE locus indicate that RelBE systems are involved in biofilm formation and reactive oxygen species (ROS) resistance. Interestingly, all seven relBE loci are induced under the standard virulence induction conditions and two of the relBE mutants displayed a colonization defect, which was not due to an effect on virulence gene expression. Although further studies are needed to characterize the mechanism of action, our study reveals that RelBE systems are important for V. cholerae physiology.