Replication slippage versus point mutation rates in short tandem repeats of the human genome

Short tandem repeats (STRs) are subjected to two kinds of mutational modifications: point mutations and replication slippages. The latter is found to be the more frequent cause of STR modifications, but a satisfactory quantitative measure of the ratio of the two processes has yet to be determined. The comparison of entire genome sequences of closely enough related species enables one to obtain sufficient statistics by counting the differences in the STR regions. We analyzed human–chimpanzee DNA sequence alignments to obtain the counts of point mutations and replication slippage modifications. The results were compared with the results of a computer simulation, and the parameters quantifying the replication slippage probability as well as the probabilities of point mutations within the repeats were determined. It was found that within the STRs with repeated units consisting of one, two or three nucleotides, point mutations occur approximately twice as frequently as one would expect on the basis of the 1.2% difference between the human and chimpanzee genomes. As expected, the replication slippage probability is negligible below a 10-bp threshold and grows above this level. The replication slippage events outnumber the point mutations by one or two orders of magnitude, but are still lower by one order of magnitude relative to the mutability of the markers that are used for genotyping purposes.     

Somatostatin-14 influences pituitary–ovarian axis in peripubertal rats

The effects of multiple somatostatin (SRIH-14) administration on the pituitary-ovarian axis were examined in peripubertal rats. Female Wistar rats received subcutaneously, two daily doses of 20 mug SRIH-14 per 100 g body weight (b.w.) for five consecutive days (from the 33rd to the 37th day of life). Follicle-stimulating (FSH), luteinizing (LH) and somatotropic (GH) cells were examined by the peroxidase-anti-peroxidase immunocytochemical method. Changes in cell volumes, volume densities and number per unit area (mm(2)) of FSH-, LH- and GH-immunoreactive cells were evaluated by stereology and morphometry. Serum FSH and LH levels were determined by RIA. Ovaries were analyzed by simple point counting of follicles. The volumes and volume densities of FSH-, LH- and GH-immunoreactive cells were significantly decreased while their numbers per mm(2) remained unchanged. SRIH-14 induced a significant decrease in serum FSH and LH levels. In the ovary, SRIH-14 induced an increase in the number of primordial follicles, followed by a reduction in the number of small healthy growing follicles and absence of preovulatory follicles. The number of atretic follicles was unchanged. We concluded that treatment with SRIH-14 during the peripubertal period markedly inhibited pituitary FSH, LH and GH cells. In the ovary, SRIH-14 acted by inhibiting folliculogenesis without affecting atretic processes.     

Gender-related differences in maximum mechanical power output in short-term activities in children and adolescents

The study was designed to examine the gender-related differences in maximum mechanical power output in various short-burst activities during growth. The subject sample consisted of four subgroups: 9 boys (14.11 +/- 0.6 yr), 9 boys (10.67 +/- 0.71 yr), 7 girls (14.29 +/- 0.49 yr), 7 girls (10.57 +/- 0.54 yr). We measured peak power (PP), mean power (MP), fatigue index (FI) during 30-s WAnT, squat jump height (SJH) and power (SJP), and counter movement jump height (CMJH) and power (CMJP), maximum speed over 20-metre distance (S20). Lactation concentration was measured in the 3rd and 5th minutes after the WAnT Ratio normalisation and ANCOVA were used to remove the influence of the differences in muscle (MM) and body mass (BM). Male adolescents had higher absolute values of PP (P < 0.05), MP (P < 0.05) than female. Ratio normalisation showed that boys had higher PP/BM (P < 0.05), PP/MM (P < 0.05), MP/BM (P < 0.05), MP/MM (P < 0.06) than girls. The ANCOVA adjustment for MM showed differences between genders in PP (P < 0.001), MP (P < 0.001), SJH (P < 0.05), SJP (P < 0.05) and CMJP (P < 0.001), whereas the ANCOVA adjustment for BM showed differences only in PP (P < 0.001), MP (P < 0.001). Prepubertal boys had higher absolute values only in SJP (P < 0.05). We concluded that variations in body composition could not be the only key to gender-related differences in power output in short-burst activities.     

A perinatal nitric oxide donor increases renal vascular resistance and ameliorates hypertension and glomerular injury in adult fawn-hooded hypertensive rats

Enhancing perinatal nitric oxide (NO) availability persistently reduces blood pressure in spontaneously hypertensive rats. We hypothesize that this approach can be generalized to other models of genetic hypertension, for instance those associated with renal injury. Perinatal exposure to the NO donor molsidomine was studied in fawn-hooded hypertensive (FHH) rats, a model of mild hypertension, impaired preglomerular resistance, and progressive renal injury. Perinatal molsidomine increased urinary NO metabolite excretion at 8 wk of age, i.e., 4 wk after treatment was stopped (P < 0.05). Systolic blood pressure was persistently reduced after molsidomine (42-wk females: 118 +/- 3 vs. 141 +/- 5 and 36-wk males: 139 +/- 4 vs. 158 +/- 4 mmHg; both P < 0.001). Perinatal treatment decreased glomerular filtration rate (P < 0.05) and renal blood flow (P < 0.01) and increased renal vascular resistance (P < 0.05), without affecting filtration fraction, suggesting persistently increased preglomerular resistance. At 4 wk of age natriuresis was transiently increased by molsidomine (P < 0.05). Molsidomine decreased glomerulosclerosis (P < 0.05). Renal blood flow correlated positively with glomerulosclerosis in control (P < 0.001) but not in perinatally treated FHH rats. NO dependency of renal vascular resistance was increased by perinatal molsidomine. Perinatal enhancement of NO availability can ameliorate development of hypertension and renal injury in FHH rats. Paradoxically, glomerular protection by perinatal exposure to the NO donor molsidomine may be due to persistently increased preglomerular resistance. The mechanisms by which increased perinatal NO availability can persistently reprogram kidney function and ameliorate hypertension deserve further study.     

Formation of noncanonical DNA structures mediated by human ORC4, a protein component of the origin recognition complex

Many genomic sequences, DNA replication origins included, contain specific structural motifs prone to alternative base pairing. Structural rearrangements of DNA require specific environmental conditions and could be favored by chemical agents or proteins. To improve our understanding of alternative conformations of origins and the manner in which they form, we have investigated the effect of DNA-binding, AAA+ protein human ORC4 on single-stranded origin DNA or various oligonucleotides. Here we demonstrate that human ORC4 stimulated formation of inter- and intramolecular T.A.T triplexes and created novel structures, such as homoadenine duplexes. Adenine-based structures were held together by Hoogsteen hydrogen bonds, as demonstrated on 7-deaza-dAMP- or dAMP-containing substrates, and characterized by increased thermal stability. Adenine pairing occurred only in the presence of human ORC4, in a neutral buffer supplemented with ATP and Mg (2+) ions. The protein mutant that could not bind ATP was inactive in this reaction. Since the action of human ORC4 could be biologically important, its potential impact on DNA replication is discussed.     

Assessing the radiological load on the environment in the middle Danube river basin on the basis of a study of the Kopački Rit Nature Park,Croatia

A study of the environmental radioactivity in the Kopa?ki Rit Nature Park, Croatia, is presented. This wildlife reserve is part of the Middle Danube River Basin, and it is exposed to various pollutants due to a number of human activities in the surroundings, where there is a nuclear power plant and also urban centres and areas of intense agricultural production. Results for the activity concentrations of soil and surface water samples do not indicate any elevated radioactivity level, which is confirmed by on-site measurements of ambient dose rate equivalent. An assessment of the radiological load on the local biota, carried out using the ERICA tool, implies an overall low radiological risk even if conservative values of the risk quotient are used. Therefore, human activities do not have a significant effect on the radiological load on the Kopa?ki Rit area. A similar conclusion might be made with regard to numerous similar environments in the Middle Danube River Basin.