Epigenetics and atherosclerosis

The contribution of epigenetic mechanisms to cardiovascular diseases remains poorly understood. Hypomethylation of genomic DNA is present in human atherosclerotic lesions and methylation changes also occur at the promoter level of several genes involved in the pathogenesis of atherosclerosis, such as extracellular superoxide dismutase, estrogen receptor-α, endothelial nitric oxide synthase and 15-lipoxygenase. So far, no clear data is available about histone modification marks in atherosclerotic lesions. It remains unclear whether epigenetic changes are causally related to the pathogenetic features, such as clonal proliferation of lesion smooth muscle cells, lipid accumulation and modulation of immune responses in the lesions, or whether they merely represent a consequence of the ongoing pathological process. However, epigenetic changes could at least partly explain poorly understood environmental and dietary effects on atherogenesis and the rapid increases and decreases in the incidence of coronary heart disease observed in various populations. RNAi mechanisms may also contribute to the epigenetic regulation of vascular cells. Therapies directed towards modification of the epigenetic status of vascular cells might provide new tools to control atherosclerosis-related cardiovascular diseases.     

Hormone response of diabetic patients to exercise at cool and warm temperatures

Both exercise and high ambient temperatures stimulate the secretion of counterregulatory hormones which can change glucose homeostasis. We studied whether in diabetic patients there are any differences in the hormonal response to exercise performed at cool or warm ambient temperatures. A study was performed on eight male insulin-dependent patients at rest and during exercise at +10 degrees C and +30 degrees C. Exercise consisted of three consecutive 15-min periods at 60% of maximal aerobic capacity. The concentrations of plasma lactate and counterregulatory hormones at rest were similar at warm and cool temperature, whereas prolactin concentration was higher (P less than 0.01) at +30 degrees C. Exercise resulted in an increase in noradrenaline, growth hormone and prolactin (P less than 0.01), prevented the diurnal decrease in cortisol, but had no effect on glucagon. Hormone responses to exercise were similar at +10 degrees C and at +30 degrees C, except for cortisol and noradrenaline which showed greater responses at warm than at cool temperatures. This may have been due to the higher relative work load at warm compared to cool temperatures as suggested by the higher heart rate and greater increase of lactate at +30 degrees C. These data indicate that within a range of ambient temperatures commonly occurring in sports, the response of counterregulatory hormones is largely independent of ambient temperature in insulin-dependent diabetic patients.     

Single-enzyme kinetics with fluorogenic substrates: lessons learnt and future directions

Single-molecule fluorescence techniques have developed into powerful tools for studying the kinetics of biological reactions at the single-molecule level. Using fluorogenic substrates, enzymatic reactions can be observed in real-time with single-turnover resolution. The turnover sequence contains all kinetic information, giving access to reaction substeps and dynamic processes such as fluctuations in the reaction rate. Despite their clearly proven potential, the accuracy of current measurements is limited by the availability of substrates with 1:1 stoichiometry and the signal-to-noise ratio of the measurement. In this review we summarize the state-of-the-art and discuss these limitations using experiments performed with α-chymotrypsin as an example. We are further providing an overview of recent efforts aimed at the improvement of fluorogenic substrates and the development of new detection schemes. These detection schemes utilize nanophotonic structures such as zero mode waveguides or nanoantennas. Nanophotonic approaches reduce the size of the effective detection volume and are a powerful strategy to increase the signal-to-noise ratio. We believe that a combination of improved substrates and novel detection schemes will pave the way for performing accurate single-enzyme experiments in biologically relevant conditions.     

Is the polyploid cranberry (Vaccinium sp.) in Finland tetraploid or hexaploid?

Only the hexaploid chromosome number of 2n=72 has been reported with convincing documentation for polyploid cranberry ( Vaccinium ) clones in Finland. Meiosis is regular in those cases which have been checked and dispersal by seeds is apparently efficient. The recent documented determinations of hexaploidy in Central Europe and N Asia and the reports in N America and N Europe may mean a circumpolar distribution of hexaploid cranberry.     

Spermidine and spermine stimulate the activity of T4-DNA ligase

When the ability of T4-DNA ligase from E. coli NM 989 to form higher molecular weight polymers from linearized plasmid pJDB 207 was followed, it was observed that physiological concentrations (0.5 to 1.0 mM) of spermidine and spermine greatly stimulated the formation of these polymers. The effect had a strict specificity since 1,3-diaminopropane, putrescine (1,4-diaminobutane) and N1-acetylspermidine neither stimulated nor inhibited this activity of DNA ligase. The structural analogues of spermidine, methyl bis(guanylhydrazone) and 1,1'-[(methylethanediylidene)dinitrilo]bis(3-aminoguanidine) totally abolished the stimulatory effect of spermidine on T4-DNA ligase without affecting the enzyme's basal activity.     

Infanticide and Population Growth in the Bank Vole (Myodes glareolus): The Effect of Male Turnover and Density

One major intrinsic factor affecting recruitment of young into a population is infanticide, the killing of conspecific young by adult males. It occurs in most mammal species, like our study species the bank vole (Myodes glareolus), and is widely accepted as an adaptive behavior, which may increase male fitness via nutritional gain, decreased competition, or an increased access to mates. A turnover of males in a population increases the risk of infanticide owing to a disruption of social structures. In a controlled field study, we tested the effects of total male turnover and density on juvenile recruitment and female space use in experimental bank vole populations. Juvenile recruitment declined significantly in low‐density populations with male turnover, while growth of high‐density populations seemed unaffected. The females’ spatial behavior seemed unaffected by both male turnover and density. Our results suggest that male infanticide may considerably affect population growth and it is more likely to do so at lower densities.     

Cysteine proteinases in chondrosarcomas

The aim of the present study was to define the role of cathepsins B, H, K, L and S in the pathogenesis of human chondrosarcomas. For this purpose 40 tumour samples obtained from 12 patients with the diagnosis of conventional chondrosarcoma were systematically investigated for the expression of cathepsin mRNAs by Northern hybridisation, and for immunohistochemical localisation of the proteins. Northern analysis demonstrated the highest levels of cathepsins B and L in a recurring grade 1 chondrosarcoma, and in a grade 3 chondrosarcoma and in fibrous histiocytomas. Increased expression of cathepsin K mRNA was seen in seven chondrosarcomas, as well as in control tumours; fibrous histiocytomas, osteosarcomas, enchondromas and a giant cell tumour of bone. Cathepsin L was immunolocalised within the large chondrocytes, while cathepsin K was predominantly localised in large multinucleated osteoclastic cells and in some hypertrophic chondrocytes. These results suggest that chondrosarcoma can be included in the growing list of tumours, where cathepsins may well be involved in tumour progression. The simultaneous upregulation of cathepsins B and L, together with matrix metalloproteinase-13, and the association of cathepsin K with negative prognostic parameters suggests that an aggressive biological behaviour of chondrosarcoma may be related to the synthesis of cysteine proteinases and activation of other proteolytic enzymes. If this turns out to be the case, cathepsin inhibitors could provide the much needed adjuvant therapy for chondrosarcomas.     

Population and community level responses in Anas -species to patch disturbance caused by an ecosystem engineer, the beaver

We studied the response of a guild of three Anas -species, to patch disturbance caused by the beaver Castor canadensis in southern Finland during 1988–1996 Of the three species, the teal Anas crecca increased in beaver ponds during the first two years of beaver occupation compared to the situation before the beaver The mallard Anas platyrhynchos and wigeon Anas penelope did not respond to beaver flooding during the first two years Also dominance relations changed upon inundation The mallard usually was more numerous than the teal before the beaver, but the reverse was the case during beaver occupation The study shows that some animal guilds may benefit from disturbance although species dominance relations may change And, that this change in dominance can be caused by an ecosystem engineer, the beaver