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.     

Secretion of Recombinant Pediocin PA-1 by Bifidobacterium longum, Using the Signal Sequence for Bifidobacterial α-Amylase

A recombinant DNA, encoding the chimeric protein of the signal sequence for bifidobacterial α-amylase mature pediocin PA-1, was introduced into Bifidobacterium longum MG1. Biologically active pediocin PA-1 was successfully secreted from the strain and showed bactericidal activity against Listeria monocytogenes and the same molecular mass as native pediocin PA-1.     

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.     

The effects of dispersal limitation and topographic heterogeneity on beta diversity and phylobetadiversity in a subtropical forest

We assessed the effects of topographic heterogeneity and stem density on species composition between grains of different sizes (20 × 20, 50 × 50, and 100 × 100 m), based on partial Mantel tests. Similarity in species composition was measured by the abundance-based Jaccard index (C_J) and by an index that incorporates phylogenetic information into C_J (pC_J). Plants were divided into five groups, arbor, subarbor, and shrub according to life form and two other groups: species that produce dry fruits (PDF) and that produce fleshy fruits (PFF). C_J and pC_J between any two grains at each grain size were calculated separately for these groups and for all species combined. In order to examine what influences C_J and pC_J, we analyzed their correlations with topographic heterogeneity variables and two dispersal limitation-related variables (stem and topographic resistance). Our data indicate that at all three grain sizes, C_J and pC_J decrease with increasing distance for all plant groups. Dispersal limitation and topographic heterogeneity were both important at 20 × 20 and 50 × 50 m grain sizes for C_J and pC_J of all plant groups; and at 100 × 100 m grain size, topographic heterogeneity dominates over dispersal limitation for some plant groups. C_J and pC_J of PDFs are less negatively correlated with stem resistance than those of PFFs. We conclude that both beta diversity and phylobetadiversity are dependent on plant groups and grain sizes.     

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.     

Immunohistochemical Identification of Met-Enkephalin in Digestive System and Its Effect on Digestive Enzyme Activities of the Scallop <Emphasis Type="Italic">Chlamys farreri</Emphasis>

The study was designed to determine whether methionine-enkephalin (M-ENK) was present in the digestive system of the scallop Chlamys farreri and investigate the effects of M-ENK on the activity of amylase, protease and lipase in the digestive system of C. farreri. The results indicated that M-ENK-like material was present in the epithelium and connective tissue of labial palps, mouth labia, stomach, intestine, rectum, and hepatopancreas of the scallop C. farreri. Moreover, it was also found that many isolated small cells showing M-ENK-like immunoreactivity were scattered in the epithelial layer of intestine, and many isolated big epithelial cells showing M-ENK-like immunoreactivity were scattered in tubules of hepatopancreas of the scallop. The activity levels of amylase and lipase in crystalline style, hepatopancreas and intestine were enhanced at 1 h after injection of exogenous M-ENK into adductor muscle of the scallops, whereas protease activity levels were significantly suppressed. Our report constitutes the first characterization of M-ENK in the digestive system of scallop C. farreri and investigates the effects of M-ENK on the activities of digestive enzymes of mollusk for the first time. The results suggest an involvement of M-ENK in the functional regulation of the digestive system of C. farreri.     

Evidence from mutation spectra that the UV hypermutability of xeroderma pigmentosum variant cells reflects abnormal, error-prone replication on a template containing photoproducts.

Xeroderma pigmentosum (XP) variant patients are genetically predisposed to sunlight-induced skin cancer. Fibroblasts derived from these patients are extremely sensitive to the mutagenic effect of UV radiation and are abnormally slow in replicating DNA containing UV-induced photoproducts. However, unlike cells from the majority of XP patients, XP variant cells have a normal or nearly normal rate of nucleotide excision repair of such damage. To determine whether their UV hypermutability reflected a slower rate of excision of photoproducts specifically during early S phase when the target gene for mutations, i.e., the hypoxanthine (guanine) phosphoribosyltransferase gene (HPRT), is replicated, we synchronized diploid populations of normal and XP variant fibroblasts, irradiated them in early S phase, and compared the rate of loss of cyclobutane pyrimidine dimers and 6-4 pyrimidine-pyrimidones from DNA during S phase. There was no difference. Both removed 94% of the 6-4 pyrimidine-pyrimidones within 8 h and 40% of the dimers within 11 h. There was also no difference between the two cell lines in the rate of repair during G1 phase. To determine whether the hypermutability resulted from abnormal error-prone replication of DNA containing photoproducts, we determined the spectra of mutations induced in the coding region of the HPRT gene of XP variant cells irradiated in early S and G1 phases and compared with those found in normal cells. The majority of the mutations in both types of cells were base substitutions, but the two types of cells differed significantly from each other in the kinds of substitutions, but the two types differed significantly from each other in the kinds of substitutions observed either in mutants from S phase (P < 0.01) or from G1 phase (P = 0.03). In the variant cells, the substitutions were mainly transversions (58% in S, 73% in G1). In the normal cells irradiated in S, the majority of the substitutions were G.C --> A.T, and most involved CC photoproducts in the transcribed strand. In the variant cells irradiated in S, substitutions involving cytosine in the transcribed strand were G.C --> T.A transversions exclusively. G.C --> A.T transitions made up a much smaller fraction of the substitutions than in normal cells (P < 0.02), and all of them involved photoproducts located in the nontranscribed strand. The data strongly suggest that XP variant cells are much less likely than normal cells to incorporate either dAMP or dGMP opposite the pyrimidines involved in photoproducts. This would account for their significantly higher frequency of mutants and might explain their abnormal delay in replicating a UV-damaged template.