Structural and functional characterization of a mutant of Pseudocerastes persicus natriuretic peptide

We hereby report on a mutational analysis of a novel natriuretic peptide (PNP), recently isolated by us from the Iranian snake venom. The PNP variant (mutPNP) with four substitutions (G16T, K18S, R21S, G23R) and a disulfide bonded ring shortened by 3 residues. mutPNP peptide was expressed in pET32 and purified by affinity separation on nickel resin followed by RP-HPLC chromatography. The conformation of mutPNP was characterized in solution by 1H nuclear magnetic resonance spectroscopy, where it was found that the 14-residue disulfide bonded ring, like the 17-residue ring in PNP, retains a high degree of conformational flexibility. The conformation of mutPNP bound to NPR-C receptor was predicted by homology protein structure modeling. When injected intravenously into rats, mutPNP, in contrast to PNP had no physiological effect on blood pressure or on diuresis. The loss of physiological activity is explained in terms of the modeled bound conformation and the ensemble of solution conformations obtained using the NMR constraints.     

A comprehensive mouse IBD database for the efficient localization of quantitative trait loci

Traditional fine-mapping approaches in mouse genetics that go from a linkage region to a candidate gene are very costly and time consuming. Shared ancestry regions, along with the combination of genetics and genomics approaches, provide a powerful tool to shorten the time and effort required to identify a causative gene. In this article we present a novel methodology that predicts IBD (identical by descent) regions between pairs of inbred strains using single nucleotide polymorphism (SNP) maps. We have validated this approach by comparing the IBD regions, estimated using different algorithms, to the results derived using the sequence information in the strains present in the Celera Mouse Database. We showed that based on the current publicly available SNP genotypes, large IBD regions (>1 Mb) can be identified successfully. By assembling a list of 21,514 SNPs in 61 common inbred strains, we inferred IBD regions between all pairs of strains and confirmed, for the first time, that existing quantitative trait genes (QTG) and susceptibility genes all lie outside of IBD regions. We also illustrated how knowledge of IBD structures can be applied to strain selection for future crosses. We have made our results available for data mining and download through a public website ( ). Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users.     

Men's approval of family planning in Bangladesh

This article attempts to evaluate men's approval of family planning in Bangladesh using the couple data set from the recent Bangladesh Demographic and Health Survey (BDHS), 1999-2000. Family planning approval is addressed both from individual and couple perspectives. Analysis of BDHS data shows that about 85% of the wives report that their husbands approve of family planning, which is lower than the wives' own approval rate (95%). Using the couple data set, husbands' characteristics were matched to the wives' responses on family planning approval. Regression analyses show that age, education, access to TV, inter-spousal communication, current use of family planning and the number of living children significantly determine family planning approval among both men as well as couples. Family planning approval was found to be much lower in Sylhet than in the other administrative divisions. Multilevel modelling analysis suggests almost negligible variation at the community level. The findings indicate the need for careful evaluation of the DHS questions in order to measure appropriately men's family planning attitudes.     

Effect of cotton cultivar on performance of Aphis gossypii (Homoptera: Aphididae) in Iran

Cotton aphids, Aphis gossypii Glover (Homoptera: Aphididae), obtained from cotton, Gossypium hirsutum L., fields in the Gorgan region of northern Iran, were colonized on 'Varamin' cotton plants in a growth chamber. The development, survivorship, and life table parameters of the cotton aphid were evaluated at 27.5 +/- 1 degrees C, 65 +/- 10% RH, and aphotoperiod of 14:10 (L:D) h of artificial light on five commonly growing cotton cultivars: Varamin, 'Sealand' (relatively resistant cultivar), 'Bakhtegan', 'Sahel' (both relatively susceptible cultivars), and 'Siokra' [resistant to Bemisia tabaci (Gennadius)]. The developmental times of immature stages ranged from 4.6 d on Bakhtegan and Varamin to 6.3 d on Sealand, whereas the immature survival was 97.5 to 65% on Sahel and Siokra, respectively. On average, there were 28.7, 28.3, 23.5, 20.1, and 16.8 nymphs produced per female on Sahel, Bakhtegan, Varamin, Sealand, and Siokra, respectively. The intrinsic rate of natural increase (r(m)) for cotton aphids on Sahel was the highest, whereas the values for r(m) varied from 0.284 (nymphs per female per d) on Siokra to 0.368 on Sahel. Jackknife estimates of generation times (T), net reproductive rate (R(0)), doubling time (DT), and finite rate of increase (lambda) on these cultivars were as follows: 9.79-10.84 d for T, 9.23-23.81 nymphs per female for R(0), 2.17-3.19 d for DT, and 1.28-1.38 nymphs per female per d for lambda. Cotton aphid performance was at its highest on Sahel and lowest on Siokra.     

Xenia effect on seed and embryo size in cotton (<Emphasis Type="Italic">Gossypium hirsutum</Emphasis> L.)

The term xenia was coined to describe the effect of foreign pollen on the development and characters of the seed. To study its importance and consequences for various seed traits in cotton (Gossypium hirsutum L.), the effect of pollen genotype on seed and embryo weight was studied with seeds from 15 F1 hybrids. Cross-fertilization changed seed weight by up to 7.0% in relation to self-fertilization. Xenia effect significantly increased embryo weight of cross-fertilized seeds, by up to 14.4% in comparison to self-fertilized seeds. Seeds of some crosses had a lower hull content than corresponding selfed seeds. On average, the xenia effect was greater for embryo weight than for seed weight. However, in some crosses there was no difference between cross- and self-fertilized seeds for seed weight, embryo weight, moisture content and hull content. Positive xenia effects for seed weight and embryo weight may help us to establish uniform stands of vigorous hybrid seedlings, especially under unfavourable conditions. Also, larger seed and embryo weight, along with lower hull content, could result in higher oil yield. Therefore, careful choosing of genotypes as parents and of cross direction in the production of hybrid seed is very important in cotton.     

Essential trace and toxic element distribution in the scalp hair of Pakistani myocardial infarction patients and controls

The pathogenesis of heart disease has been associated with changes in the balance of certain trace elements. The aim of this study was to evaluate the Zn, Fe, Cu, Cr, Ni, Pb, and Cd contents in scalp hair samples of myocardial infarction (MCI) patients hospitalized in the cardiac ward of National Hospital in Hyderabad city (Pakistan). Scalp hair samples were collected from 193 patients (104 male, 89 female) of 3 age groups (46–60, 61–75, and 76–90 yr), for a comparative study, 200 normal, healthy subjects (103 male, 97 female) of the same age groups residing in the same city were selected. All metals in scalp hair samples were assessed by a flame/graphite furnace atomic absorption spectrophotometer, prior to microwave-assisted and conventional wet acid digestion methods. Results were calculated in micrograms per gram. The mean values of Fe and Zn of scalp hair samples of MCI patients were significantly reduced compared to the control subjects of both genders. The mean Fe concentrations in male patients were 19.42, 12.36, and 6.98 vs 30.69, 24.42, and 16.75 for the control patients in the three age groups (46–60, 61–75, and 76–90 yrs, respectively). The mean Zn concentration in male patients were 169.2, 149.4, and 107.7 μg/g vs 206.1, 188.0, and 154.4 μg/g for the control group (p<0.002, 0.004, and 0.001) in all three age groups, respectively. These differences were also observed in the female study groups. The mean values of Pb, Cd, and Ni were significantly high in patients compared to healthy subjects (mean Pb in male patients: 11.85, 12.89, and 14.52 those of female patients were 11.88, 12.73, and 14.21 vs the male controls patients (6.08, 7.56, and 8.56) and female controls (5.99, 7.41, and 8.25) for all three age groups, respectively. The concentration of Ni and Cd in the scalp hair samples of the heart patients of both sexes were significantly higher compared to the control; in the case of Ni the range of significant difference for males was found to be p<0.001–0.009 and for females to be p<0.0.002–0.007 and significantly high concentration of Cd were observed in hair samples of patients than in controls in the range for males (p<0.001–0.009) and in females (p<0.001–0.011). The Zn/Cu and Zn/Cd ratios in the scalp hair (p<0.01) of the diseased groups were significantly lower than that of the healthy groups. Deficiency of essential trace metals and high level of toxic metals might play a role in the development of heart disease in the subjects of this study. Toxic metals might also cause diminished absorption of essential elements.     

Growth hormone receptor deficiency results in blunted ghrelin feeding response, obesity, and hypolipidemia in mice

We have previously shown that growth hormone (GH) overexpression in the brain increased food intake, accompanied with increased hypothalamic agouti-related protein (AgRP) expression. Ghrelin, which stimulates both appetite and GH secretion, was injected intracerebroventricularly to GHR-/- and littermate control (+/+) mice to determine whether ghrelin's acute effects on appetite are dependent on GHR signaling. GHR-/- mice were also analyzed with respect to serum levels of lipoproteins, apolipoprotein (apo)B, leptin, glucose, and insulin as well as body composition. Central injection of ghrelin into the third dorsal ventricle increased food consumption in +/+ mice, whereas no change was observed in GHR-/- mice. After ghrelin injection, AgRP mRNA expression in the hypothalamus was higher in +/+ littermates than in GHR-/- mice, indicating a possible importance of AgRP in the GHR-mediated effect of ghrelin. Compared with controls, GHR-/- mice had increased food intake, leptin levels, and total and intra-abdominal fat mass per body weight and deceased lean mass. Moreover, serum levels of triglycerides, LDL and HDL cholesterol, and apoB, as well as glucose and insulin levels were lower in the GHR-/- mice. In summary, ghrelin's acute central action to increase food intake requires functionally intact GHR signaling. Long-term GHR deficiency in mice is associated with high plasma leptin levels, obesity, and increased food intake but a marked decrease in all lipoprotein fractions.     

Plasma kisspeptin is raised in patients with gestational trophoblastic neoplasia and falls during treatment

Kisspeptin is a 54-amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates G protein-coupled receptor 54 (GPR54). The kisspeptin-GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy, but levels in GTN have not previously been reported. The present study was designed to determine whether plasma kisspeptin levels are altered in patients with malignant GTN. Thirty-nine blood samples were taken from 11 patients with malignant GTN at presentation during and after chemotherapy. Blood was also sampled from nonpregnant and pregnant volunteers. Plasma kisspeptin IR and hCG concentrations were measured. Plasma kisspeptin IR concentration in nonpregnant (n = 16) females was <2 pmol/l. Plasma kisspeptin IR in females was 803 +/- 125 pmol/l in the first trimester of pregnancy (n = 13), 2,483 +/- 302 pmol/l in the third trimester of pregnancy (n = 7), and <2 pmol/l on day 15 postpartum (n = 7). Plasma kisspeptin IR and hCG concentrations in patients with malignant GTN were elevated at presentation and fell during and after treatment with chemotherapy in each patient (mean plasma kisspeptin IR: prechemotherapy 1,363 +/- 1,076 pmol/l vs. post-chemotherapy <2 pmol/l, P < 0.0001; mean plasma hCG: prechemotherapy 227,191 +/- 152,354 U/l vs. postchemotherapy 2 U/l, P < 0.0001). Plasma kisspeptin IR strongly positively correlated with plasma hCG levels (r(2) = 0.99, P < 0.0001). Our results suggest that measurement of plasma kisspeptin IR may be a novel tumor marker in patients with malignant GTN.