Bivariate variance-component analysis, with application to systolic blood pressure and total cholesterol levels in the Framingham Heart Study

Background :
The correlations between systolic blood pressure (SBP) and total cholesterol levels (CHOL) might result from genetic or environmental factors that determine variation in the phenotypes and are shared by family members. Based on 330 nuclear families in the Framingham Heart Study, we used a multivariate normal model, implemented in the software FISHER, to estimate genetic and shared environmental components of variation and genetic and shared environmental correlation between the phenotypes. The natural logarithm of the phenotypes measured at the last visit in both Cohort 1 and 2 was used in the analyses. The antihypertensive treatment effect was corrected before adjustment of the systolic blood pressure for age, sex, and cohort.
Results :
The univariate correlation coefficient was statistically significant for sibling pairs and parent-offspring pairs, but not significant for spouse pairs. In the bivariate analysis, the cross-trait correlation coefficients were not statistically significant for all relative pairs. The shared environmental correlation was statistically significant, but the genetic correlation was not significant.
Conclusion :
There is no significant evidence for a close genetic correlation between systolic blood pressure and total cholesterol levels. However, some shared environmental factors may determine the variation of both phenotypes.

Familial and genomic analyses of postural changes in systolic and diastolic blood pressure

The physiological adaptation to the erect posture involves integrated neural and cardiovascular responses that might be determined by genetic factors. We examined the familial- and individual-specific components of variance for postural changes in systolic and diastolic blood pressure in 767 volunteer nuclear adult families from the Victorian Family Heart Study. In 274 adult sibling pairs, we made a genome-wide scan using 400 markers for quantitative trait loci linked with the postural changes in systolic and diastolic pressures. Overall, systolic pressure did not change on standing, but there was considerable variation in this phenotype (SD=8.1 mm Hg). Familial analyses revealed that 25% of the variance of change in systolic pressure was attributable to genetic factors. In contrast, diastolic pressure increased by 6.3 mm Hg (SD=7.0 mm Hg) on standing and there was no evidence of contributory genetic factors. Multipoint quantitative genome linkage mapping suggested evidence (Z=3.2) of linkage of the postural change in systolic pressure to chromosome 12 but found no genome-wide evidence of linkage for the change in diastolic pressure. These findings suggest that genetic factors determine whether systolic pressure decreases or increases when one stands, possibly as the result of unidentified alleles on chromosome 12. The genetics of postural changes in systolic blood pressure might reflect the general buffering function of the baroreflex; thereby, the predisposition to sudden decreases or increases in systolic pressure might cause postural hypotension or vessel wall disruption, respectively.

Renal C-type natriuretic peptide and natriuretic peptide receptor B mRNA expression are affected by water deprivation in the Spinifex Hopping mouse

This study investigated the effect of water deprivation on the expression of C-type natriuretic peptide (CNP) and natriuretic peptide receptor B (NPR-B) mRNA, and the ability of NPR-B to generate cGMP in the Spinifex Hopping mouse, Notomys alexis. This rodent is a native of central and western Australia that is well adapted to survive in arid environments. Initially, CNP and NPR-B cDNAs (partial for NPR-B) were cloned and sequenced, and were shown to have high homology with those of rat and mouse. RT-PCR analysis showed CNP mRNA expression in the kidney, proximal and distal colon and small intestine, whilst NPR-B mRNA expression was found in the kidney, proximal and distal colon and the atria. Using a semi-quantitative multiplex PCR technique, the expression of renal CNP and NPR-B mRNA was determined in 7- and 14-day water-deprived hopping mice, in parallel with control hopping mice (access to water). Water deprivation significantly decreased the relative levels of CNP and NPR-B mRNA expression in both the 7- and 14-day water-deprived hopping mice, when compared to control hopping mice. In contrast, the ability of CNP to stimulate cGMP production was significantly increased after 14 days of water deprivation. This study shows that alterations in the renal CNP/NPR-B system may be an important physiological adjustment when water is scarce.

Kinetic analysis of the interaction of the copper chaperone Atox1 with the metal binding sites of the Menkes protein

Excess copper is effluxed from mammalian cells by the Menkes or Wilson P-type ATPases (MNK and WND, respectively). MNK and WND have six metal binding sites (MBSs) containing a CXXC motif within their N-terminal cytoplasmic region. Evidence suggests that copper is delivered to the ATPases by Atox1, one of three cytoplasmic copper chaperones. Attempts to monitor a direct Atox1-MNK interaction and to determine kinetic parameters have not been successful. Here we investigated interactions of Atox1 with wild-type and mutated pairs of the MBSs of MNK using two different methods: yeast two-hybrid analysis and real-time surface plasmon resonance (SPR). A copper-dependent interaction of Atox1 with the MBSs of MNK was observed by both approaches. Cys to Ser mutations of conserved CXXC motifs affected the binding of Atox1 underlining the essentiality of Cys residues for the copper-induced interaction. Although the yeast two-hybrid assay failed to show an interaction of Atox1 with MBS5/6, SPR analysis clearly demonstrated a copper-dependent binding with all six MBSs highlighting the power and sensitivity of SPR as compared with other, more indirect methods like the yeast two-hybrid system. Binding constants for copper-dependent chaperone-MBS interactions were determined to be 10–5-10–6 M for all the MBSs representing relatively low affinity binding events. The interaction of Atox1 with pairs of the MBSs was non-cooperative. Therefore, a functional difference of the MBSs in the MNK N terminus cannot be attributed to cooperativity effects or varying affinities of the copper chaperone Atox1 with the MBSs.

Blood pressure change with weight loss is affected by diet type in men

Background: Weight loss reduces blood pressure, and the Dietary Approaches to Stop Hypertension (DASH) diet has also been shown to lower blood pressure.

Objective: Our goal was to assess the effect on blood pressure of 2 weight-reduction diets: a low-fat diet (LF diet) and a moderate-sodium, high-potassium, high-calcium, low-fat DASH diet (WELL diet).

Design: After baseline measurements, 63 men were randomly assigned to either the WELL or the LF diet for 12 wk, and both diet groups undertook 0.5 h of moderate physical activity on most days of the week.

Results: Fifty-four men completed the study. Their mean (±SD) age was 47.9 ± 9.3 y (WELL diet, n = 27; LF diet, n = 27), and their mean baseline home systolic and diastolic blood pressures were 129.4 ± 11.3 and 80.6 ± 8.6 mm Hg, respectively. Body weight decreased by 4.9 ± 0.6 kg (±SEM) in the WELL group and by 4.6 ± 0.6 kg in the LF group (P < 0.001 for both). There was a greater decrease in blood pressure in the WELL group than in the LF group [between-group difference (week 12 –baseline) in both SBP (5.5 ± 1.9 mm Hg; P = 0.006) and DBP (4.4 ± 1.2 mm Hg; P = 0.001)].

Conclusions: For a comparable 5-kg weight loss, a diet high in low-fat dairy products, vegetables, and fruit (the WELL diet) resulted in a greater decrease in blood pressure than did the LF diet. This dietary approach to achieving weight reduction may confer an additional benefit in reducing blood pressure in those who are overweight.

The social consequences of 'how the sibling died' for bereaved young adults

Research into how the 'type' of sibling death impacts surviving siblings at a social level was conducted using a semi-structured interview format with 25 bereaved siblings and seven counsellors. The results indicated that in cases where a sibling's death had a greater impact within public spheres, the young adult was more likely to receive beneficial social support than young adults associated with 'private' death examples. The paper concludes by outlining how individuals can provide effective support for bereaved young adults, as well as avoid unhelpful support behaviours.

Zero impact: are lawyers' values affected by law school?(Survey)

In 2001 approximately 700 Australian final-year undergraduate law students were surveyed as the first part of a three-year study of Australian lawyers' values. This study is being undertaken in an effort to understand what values are important in determining lawyers' attitudes to difficult behavioural choices confronting them in legal practice. It is hoped that knowledge of the actual values held by lawyers (in the context of critical professional choices) will enable better targeted values awareness education in both pre- and post-admission contexts.

The main quantitative survey employed a number of hypothetical scenarios. These were designed through the use of ethical dilemmas to examine issues of conflicting loyalties within a context of self-interest and lawyers' perceived obligations to the community, employers, family, friends and clients. (1)

Our approach in this paper is to set the scene by providing basic frequencies to responses in each scenario, followed by an analysis of themes elicited from respondents during the focus groups. Our immediate objective is to provide representative interviewee (that is, respondent) commentary designed to throw some light on the major choices of those respondents in the first year of the main quantitative survey. (2) Note that these focus groups were conducted some months after the quantitative analyses, and in particular after respondents had left law school. All respondents were, by that stage, working within a variety of legal workforce environments. In this analysis, it must be stressed, we have not attempted to match and compare individual respondents' comments with their earlier choices in the quantitative survey. That task awaits the longitudinal analysis now under way for the whole period of data collection during the three-year study.

Sibling peer support group for young people with a sibling using drugs: a pilot study

Siblings of young people abusing drugs are at particular risk for drug abuse and other health compromising behaviors. A Sibling Peer Support Group was developed by the Centre for Adolescent Health (Melbourne, Australia) for young people aged 13 to 18 years with a problematic drug user in their family. Groups aimed to provide support and information, promote harm minimization, and reduce the sense of isolation. The project emanated from the recognized need for specific support for adolescent siblings of problematic drug users. Evaluation of two pilot groups indicated positive benefits for group members, who reported feeling better informed, more supported, and having a reduced sense of isolation. Parents reported that their adolescent attending the group demonstrated improved communication with, and greater understanding and tolerance of, the family member using drugs. Promising indicators at a community level were manifested in enthusiastic collaboration among schools, police and local service agencies, and the organization of a local drug forum. There appeared to be little evidence that the groups inadvertently encouraged drug use. Recruitment of young people into groups was the major challenge for the project, but among drug and alcohol and family organizations there was support for the concept of a Sibling Peer Support Group. A new model to overcome the challenge of recruitment is proposed.

Growth and product quality of European eel (Anguilla anguilla) as affected by dietary protein and lipid sources

A 12-week feeding trial was undertaken to evaluate the effects of partial replacement of marine raw materials in the diet with soybean meal and beef tallow on growth and product quality of European eel (Anguilla anguilla ). Based on growth, feed efficiency and chemical composition, soybean meal was found to be an unsuitable ingredient for eel diets as a substitute for fishmeal (25% on a protein basis), probably because of the low digestibility of its carbohydrate content. However, beef tallow can be used to replace 50% of fish oil without reduction in growth, provided that digestible carbohydrates are present in the diet. No major effects of protein and lipid sources in the diet were found on fillet chemical composition. Sensory analysis revealed no significant differences between fish fed the control and the experimental diets, with the exception of salty taste which was significantly higher in fish fed combined soybean meal and beef tallow compared with fish fed the control diet.

The role of sisters in body image dissatisfaction and disordered eating

The Tripartite Influence Model (TIM) argues sociocultural agents affect body image dissatisfaction (BID) via the mediators of social comparison and internalization. BID subsequently influences disordered eating. Forty-seven Australian sister pairs (18–25 years) provided self-reports of perceived familial modeling and pressure by the sociocultural agents of mother, father and sister, social comparison, internalization, BID, bulimic behaviors, and dietary restriction. Sisters were correlated on internalization, BID, disordered eating, and parental modeling and pressure. Mothers and sisters were equally important modeling agents. Sisters were an equivalent social comparison target to peers. Consistent with the TIM, internalization and social comparison mediated familial pressure on BID. Contrary to the model, sister modeling directly affected bulimic behaviors and dietary restriction.

Osmoregulatory balance in Murray cod, Maccullochella peelii peelii (Mitchell), affected with chronic ulcerative dermatopathy

This study examined the osmoregulatory capability of Murray cod, Maccullochella peelii peelii, affected by chronic ulcerative dermatopathy (CUD) in intensive aquaculture. This condition appears to arise only in facilities utilizing groundwater, with the causative agent suggested to be a water-borne factor. Healthy Murray cod (~ 700 g) were transferred to a CUD-affected farm to monitor the progression of the syndrome and began to show signs of CUD after approximately five months. In order to evaluate possible effects of CUD on osmoregulation; plasma electrolyte concentrations, osmolality, and Na⁺,K⁺-ATPase activities were measured, and gill histology and immunohistochemistry were analyzed. Plasma electrolyte concentrations and osmolality of CUD-affected Murray cod were consistent with reference values determined for non CUD-affected fish. A greater number of gill mucous cells were observed in Murray cod cultured at the CUD-affected farm compared to non CUD-affected fish. We also found an un-identified cell type that was present solely in the gills of CUD-affected Murray cod. Gill Na⁺,K⁺-ATPase activity was significantly higher in severely CUD-affected Murray cod compared to individuals transferred to the CUD-affected farm. While there appeared to be some minor changes in the gills of CUD-affected fish, this study demonstrated that Murray cod were able to effectively osmoregulate, although, perhaps at an energetic cost.

Interacting amino acid preferences of 3D pattern pairs at the binding sites of transient and obligate protein complexes

To assess the physico-chemical characteristics of protein-protein interactions, protein sequences and overall structural folds have been analyzed previously. To highlight this, discovery and examination of amino acid patterns at the binding sites defined by structural proximity in 3-dimensional (3D) space are essential. In this paper, we investigate the interacting preferences of 3D pattern pairs discovered separately in transient and obligate protein complexes. These 3D pattern pairs are not necessarily sequence-consecutive, but each residue in two groups of amino acids from two proteins in a complex is within certain °A threshold to most residues in the other group. We develop an algorithm called AA-pairs by which every pair of interacting proteins is represented as a bipartite graph, and it discovers all maximal quasi-bicliques from every bipartite graph to form our 3D pattern pairs. From 112 and 2533 highly conserved 3D pattern pairs discovered in the transient and obligate complexes respectively, we observe that Ala and Leu is the highest occuring amino acid in interacting 3D patterns of transient (20.91%) and obligate (33.82%) complexes respectively. From the study on the dipeptide composition on each side of interacting 3D pattern pairs, dipeptides Ala-Ala and Ala-Leu are popular in 3D patterns of both transient and obligate complexes. The interactions between amino acids with large hydrophobicity difference are present more in the transient than in the obligate complexes. On contrary, in obligate complexes, interactions between hydrophobic residues account for the top 5 most occuring amino acid pairings.