The role of cognitive vulnerability and stress in the prediction of postpartum depressive symptomatology

Objectives. The present study was designed to test the diathesis-stress components of Beck's cognitive theory of depression and the reformulated learned helplessness model of depression in the prediction of postpartum depressive symptomatology. Design and methods. The research used a two-wave longitudinal design-data were collected from 65 primiparous women during their third trimester of pregnancy and then 6 weeks after the birth. Cognitive vulnerability and initial depressive symptomatology were assessed at Time 1, whereas stress and postpartum depressive symptomatology were assessed at Time 2. Results. There was some support for the diathesis-stress component of Beck's cognitive theory, to the extent that the negative relationship between both general and maternal-specific dysfunctional attitudes associated with performance evaluation and Time 2 depressive symptomatology was strongest for women who reported high levels of parental stress. In a similar vein, the effects of dysfunctional attitudes (general and maternal-specific) associated with performance evaluation and need for approval (general measure only) on partner ratings of emotional distress were evident only among those women whose infants were rated as being temperamentally difficult. Conclusion. There was no support for the diathesis-stress component of the reformulated learned helplessness model of depression; however, there was some support for the diathesis-stress component of Beck's cognitive theory.

Barriers to equality: men's and women's attitudes to workplace entitlements in Australia

This paper examines attitudes to workplace entitlements, such as parental leave and flexible work hours. Family friendly policies such as leave to care for children have implications for feminist debates about sameness versus difference and the extent to which such policies will lead to greater equality between men and women, or alternatively, further entrench existing gender divisions of labour: Using data from a recent national survey in Australia, the paper shows that while the Australian workforce is generally in favour of workplace entitlements, women are generally more supportive of these kinds of benefits than men. Surprisingly, most respondents are more supportive of unpaid rather than paid parental leave. The results also show that the most important determinants of support for work entitlements are a combination of the extent to which one needs work entitlements and employment location. The results raise issues about whether the provision of workplace entitlements will encourage greater participation by men in domestic responsibilities, or simply ease women's double burden of paid and unpaid work.

Evolution of local recruitment and its consequences for marine populations

Advantages of dispersal on the scales that are possible in a long pelagic larval period are not apparent, even for benthic species. An alternative hypothesis is that wide dispersal may be an incidental byproduct of an ontogenetic migration from and then back to the parental habitat. Under this hypothesis, the water column is a better habitat than the bottom for early development. Because the parental area is often an especially favorable habitat for juveniles and adults, selection may even favor larval retention or larval return rather than dispersal. Where larval capabilities and currents permit, a high percentage of recruits may then be produced from local adults. Expected consequences of a high proportion of local recruitment are stronger links between stock and recruitment, greater vulnerability to recruitment overfishing and local modifications of habitat, greater local benefits from fishery reserves, and possibly more localized adaptation within populations. Export of some larvae is consistent with a high proportion of retained or returning larvae, could stabilize populations linked by larval exchange, and provide connectivity between marine reserves. Even a small amount of larval export could account for the greater gene flow, large ranges, and long evolutionary durations seen in species with long pelagic larval stages.

Directed evolution of mammalian cytochrome P450 enzymes involved in xenobiotic metabolism

Directed evolution of cytochrome P450 enzymes represents an attractive means of generating novel catalysts for specialized applications. Xenobiotic-metabolizing P450s are particularly well suited to this approach due to their inherent wide substrate specificity. In the present study, a novel method for DNA shuffling was developed using an initial restriction enzyme digestion step, followed by elimination of long parental sequences by size-selective filtration. P450 2C forms were subjected to a single round of shuffling then coexpressed with reductase in E. coli. A sample (54 clones) of the resultant library was assessed for sequence diversity, hemo- and apoprotein expression, and activity towards the substrate indole. All mutants showed a different RFLP pattern compared to all parents, suggesting that the library was free from contamination by parental forms. Haemoprotein expression was detectable in 45/54 (83%) of the mutants sampled. Indigo production was less than or comparable to the activities of one or more of the parental P450s, but three mutants showed indirubin production in excess of that seen with any parental form, representing a gain of function. In conclusion, a method is presented for the effective shuffling of P450 sequences to generate diverse libraries of mutant P450s containing a high proportion of correctly folded hemoprotein, and minimal contamination with parental forms.

Ancestry informative markers in Amerindians from Brazilian Amazon

Ancestry informative markers (AIMs) are genetic loci with large frequency differences between the major ethnic groups and are very useful in admixture estimation. However, their frequencies are poorly known within South American indigenous populations, making it difficult to use them in admixture studies with Latin American populations, such as the trihybrid Brazilian population. To minimize this problem, the frequencies of the AIMs FY-null RB2300, LPL, AT3-1/1), Sb19.3, APO, and PV92 were determined via PCR and PCR-RFLP in four tribes from Brazilian Amazon (Tikuna, Kashinawa, Baniwa, and Kanamari), to evaluate their potential for discriminating indigenous populations from Europeans and Africans, as well as discriminating each tribe from the others. Although capable of differentiating tribes, as evidenced by the exact test of population differentiation, a neighbor-joining tree suggests that the AIMs are useless in obtaining reliable reconstructions of the biological relationships and evolutionary history that characterize the villages and tribes studied. The mean allele frequencies from these AIMs were very similar to those observed for North American natives. They discriminated Amerindians from Africans, but not from Europeans. On the other hand, the neighbor-joining dendrogram separated Africans and Europeans from Amerindians with a high statistical support (bootstrap = 0.989). The relatively low diversity (GST = 0.042) among North American natives and Amerindians from Brazilian Amazon agrees with the lack of intra-ethnic variation previously reported for these markers. Despite genetic drift effects, the mean allelic frequencies herein presented could be used as Amerindian parental frequencies in admixture estimates in urban Brazilian populations.

Geographical variation in offspring size effects across generations

Offspring size is thought to strongly affect offspring fitness and many studies have shown strong offspring size/fitness relationships in marine and terrestrial organisms. This relationship is strongly mitigated by local environmental conditions and the optimal offspring size that mothers should produce will vary among different environments. It is assumed that offspring size will consistently affect the same traits among populations but this assumption has not been tested. Here I use a common garden experiment to examine the effects of offspring size on subsequent performance for the marine bryozoan Bugula neritina using larvae from two very different populations. The local conditions at one population (Williamstown) favour early reproduction whereas the other population (Pt. Wilson) favours early growth. Despite being placed in the same habitat, the effects of parental larval size were extremely variable and crossed generations. For larvae from Williamstown, parental larval size positively affected initial colony growth and larval size in the next generation. For larvae from the other population, parental larval size positively affected colony fecundity and negatively affected larval size in the next generation. Traditionally, exogenous factors have been viewed as the sole source of variation in offspring size/fitness relationship but these results show that endogenous factors (maternal source population) can also cause variation in this crucial relationship. It appears offspring size effects can be highly variable among populations and organisms can adapt to local conditions without changing the size of their offspring.

Association between dopamine transporter (DATI) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention-deficit hyperactivity disorder

A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with attention-deficit hyperactivity disorder (ADHD) and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. A total of 43 ADHD children and their parents were genotyped for the DAT1 30 variable number of tandem repeats polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index ( leftward to rightward attentional bias). Parents rated their child's response to MPH retrospectively using a three-point scale ( no, mediocre or very good response). Additionally, parents used a symptom checklist to rate behavior while on and off medication. A within-family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to MPH. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a subgroup of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.

Cognitive deficits, length of illness and symptom severity in schizophrenia

Background Research using neuropsychological testing has demonstrated that patients with schizophrenia show deficits in multiple neurocognitive domains. The aim of this study is to identify cognitive deficits that correlate with length of illness and symptom severity. Method Twenty clinically stable outpatients with chronic schizophrenia (18M : 2F) and 14 healthy controls (13M : 1F), matched on age, gender and parental education, were administered a neuropsychological battery consisting of the Hayling Sentence Completion Test (HSCT), WMS-III Verbal Paired Associates & Letter Number Sequencing, Modified Card Sort Test (MCST), Pyramids & Palm Trees Test, National Adult Reading Test (NART), Controlled Oral Word Association Test (COWAT), and WAIS-III. Severity of symptoms was rated with the Structured Clinical Interview – Positive and Negative Syndromes Scale (SCI-PANSS). Results In comparison to controls, patients showed significant deficits on all of the neuropsychological tasks except for the COWAT. MCST total categories, NART, Verbal IQ and arithmetic, similarities & digit symbol of the WAIS-III had the largest effect size between the groups. The longer the illness duration, the poorer the performance on WAISIII block design and the lower the performance IQ score. The poorer the performance on WMS-III letter number sequencing, the greater the positive symptoms, negative symptoms and general psychopathology. Conclusion Compared to controls, patients showed large effect sizes on measures of executive functioning, intelligence, working memory, verbal comprehension and speed of processing. The findings suggest that impairment in executive functioning and performance IQ is associated with length of illness, while impairment in working memory is associated with heightened symptom severity.

Evidence that two independent host genes influence the severity of tissue damage and susceptibility to acute pyelonephritis in murine systemic candidiasis

Tissue damage in the kidney and brain after systemic infection with Candida albicans was examined in recombinant inbred strains (AKXL) derived from AKR and C57/L progenitors. Nine of the 15 strains showed mild (C57/L-like) tissue damage. Of the remainder, two strains developed lesions comparable to the AKR parental strain, whereas four exhibited a much move severe pattern of tissue damage. This was characterized by pronounced mycelial growth in the brain, and gross oedema of the kidney, with extensive fungal colonization and marked tissue destruction. The presence of the null allele of the haemolytic complement gene (Hc) may be necessary but not sufficient, for the expression of the very severe lesions. The results were interpreted as reflecting the actions of two independent genes, which have been designated Carg1 and Carg2 (Candida albicans resistance genes 1 and 2). (C) 1997 Academic Press Limited.

E7 oncoprotein of human papillomavirus type 16 expressed constitutively in the epidermis has no effect on E7-specific B- or Th-repertoires or on the immune response induced or sustained after immunization with E7 protein

A line of FVB (H-2(q)) mice transgenic for the E6/E7 open reading frames of Human Papillomavirus type 16 driven from the alpha-A crystallin promoter expresses E7 mRNA in lens and skin epithelium. E7 protein is detectable in adult skin, coinciding with the development or inflammatory skin disease, which progresses to papillomata and squamous carcinomata in some mice. By examining the outcome of parenteral immunization with E7 protein, we sought to determine whether endogenous expression of E7 in skin had induced a preexisting immune outcome, i.e., specific immunity or tolerance, or whether the mice remain naive (''ignorant'') to E7. Our data show that the antibody response to defined E7 B-epitopes, the proliferative response to Th epitopes, and the delayed-type hypersensitivity (DTH) response to whole E7 did not differ between groups or young and old E6/E7 transgenic mice (likely having different degrees of lifetime exposure to E7 protein) or between E6/E7-transgenic and nontransgenic parental strain control mice. Although an E7-specific CTL response could not be induced in the H-2(q) background of these mice, incorporation of a D-b allele into the genome allowed comparison of D-b-restricted CTL responses in E6/E7 transgenic and nontransgenic mice. Experiments indicated that the E7-immunization-induced CTL response did not differ significantly between E6/E7 transgenic and nontransgenic mice. We interpret these results to indicate that in spite of expression of E7 protein in adult skin, E6/E7 transgenic mice remain immunologically naive (ignorant) of E7 epitopes presented by immunization. (C) 1997 Academic Press.

Effects of high-intensity aerobic interval training vs. moderate exercise on hemodynamic, metabolic and neuro-humoral abnormalities of young normotensive women at high familial risk for hypertension

Exercise training has an important role in the prevention and treatment of hypertension, but its effects on the early metabolic and hemodynamic abnormalities observed in normotensive offspring of hypertensive parents (FH+) have not been studied. We compared high-intensity interval (aerobic interval training, AIT) and moderate-intensity continuous exercise training (CMT) with regard to hemodynamic, metabolic and hormonal variables in FH+ subjects. Forty-four healthy FH+ women (25.0+/-4.4 years) randomized to control (ConFH+) or to a three times per week equal-volume AIT (80-90% of VO(2MAX)) or CMT (50-60% of VO(2MAX)) regimen, and 15 healthy women with normotensive parents (ConFH-; 25.3+/-3.1 years) had their hemodynamic, metabolic and hormonal variables analyzed at baseline and after 16 weeks of follow-up. Ambulatorial blood pressure (ABP), glucose and cholesterol levels were similar among all groups, but the FH+ groups showed higher insulin, insulin sensitivity, carotid-femoral pulse wave velocity (PWV), norepinephrine and endothelin-1 (ET-1) levels and lower nitrite/ nitrate (NOx) levels than ConFH- subjects. AIT and CMT were equally effective in improving ABP (P<0.05), insulin and insulin sensitivity (P<0.001); however, AIT was superior in improving cardiorespiratory fitness (15 vs. 8%; P<0.05), PWV (P<0.01), and BP, norepinephrine, ET-1 and NOx response to exercise (P<0.05). Exercise intensity was an important factor in improving cardiorespiratory fitness and reversing hemodynamic, metabolic and hormonal alterations involved in the pathophysiology of hypertension. These findings may have important implications for the exercise training programs used for the prevention of inherited hypertensive disorder. Hypertension Research (2010) 33, 836-843; doi:10.1038/hr.2010.72; published online 7 May 2010

Behavior Profile of Family Members of Donors and Nondonors of Organs

Organ transplant shortage is a global problem caused by several factors, most of which are related to members of the family, who play it major role in the donation process. Objective. We sought to determine the most determinant features in the donor profile that relate to positive decisions versus refusal of donation. Material and Methods. Fifty-six families who were approached by the Organ Procurement Organization (OPO) from November 2004 to April 2006 agreed to participate in this work. To assess donor profiles, we used it structured interview. Results. Parental involvement directly in decisions about donation lead to significantly less frequent consent (P = .005), young donor age was associated with a reduced probability of donation (P = .002), violent death negatively influenced donation consent, excluding suicide (P = .004). Conclusion. The present study showed violent death, young patient age, and parental donation consent to be the most important factors that make it harder to obtain consent organ donation. When a collateral relative (sibling/uncle) or children were responsible for the donation decision, there was more success of consent.

Sialylation of beta 1 Integrins blocks cell adhesion to galectin-3 and protects cells against galectin-3-induced apoptosis

In previous studies, we determined that beta 1 integrins from human colon tumors have elevated levels of alpha 2-6 sialylation, a modification added by beta-galactosamide alpha-2,6-sialyltranferase I (ST6Gal-I). Intriguingly, the beta 1 integrin is thought to be a ligand for galectin-3 (gal-3), a tumor-associated lectin. The effects of gal-3 are complex; intracellular forms typically protect cells against apoptosis through carbohydrate-independent mechanisms, whereas secreted forms bind to cell surface oligosaccharides and induce apoptosis. In the current study, we tested whether alpha 2-6 sialylation of the beta 1 integrin modulates binding to extracellular gal-3. Herein we report that SW48 colonocytes lacking alpha 2-6 sialylation exhibit beta 1 integrin-dependent binding to gal-3-coated tissue culture plates; however, binding is attenuated upon forced expression of ST6Gal-I. Removal of alpha 2-6 sialic acids from ST6Gal-I expressors by neuraminidase treatment restores gal-3 binding. Additionally, using a blot overlay approach, we determined that gal-3 binds directly and preferentially to unsialylated, as compared with alpha 2-6-sialylated, beta 1 integrins. To understand the physiologic consequences of gal-3 binding, cells were treated with gal-3 and monitored for apoptosis. Galectin-3 was found to induce apoptosis in parental SW48 colonocytes ( unsialylated), whereas ST6Gal-I expressors were protected. Importantly, gal-3-induced apoptosis was inhibited by function blocking antibodies against the beta 1 subunit, suggesting that beta 1 integrins are critical transducers of gal-3-mediated effects on cell survival. Collectively, our results suggest that the coordinate up-regulation of gal-3 and ST6Gal-I, a feature that is characteristic of colon carcinoma, may confer tumor cells with a selective advantage by providing a mechanism for blockade of the pro-apoptotic effects of secreted gal-3.

Expression of constitutively activated human c-Kit in myb transformed early myeloid cells leads to factor independence, histiocytic differentiation, and tumorigenicity

The cDNAs encoding wild type (WT) human receptor tyrosine kinase c-Kit and a constitutively activated mutant, V816Kit, were introduced into granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent early murine hemopoietic cells, which had been transformed with activated Myb, WTKit cells were able to grow in the presence of the human ligand for Kit, stem cell factor (SCF), but displayed reduced growth and clonogenic potential in either SCF or GM-CSF compared with the parental cells in GM-CSF. In contrast, V816Kit cells grew without factor at a higher rate than the parental cells in GM-CSF and displayed increased clonogenicity. Dissection of the growth characteristics in liquid culture showed that in the presence of appropriate factors, the different populations had similar proliferation rates, but that V816Kit profoundly increased cell survival compared with WTKit or parental cells, This suggests that the signals transduced by WTKit activated with SCF, and by V816Kit, were not identical. Also, WTKit and V816Kit-expressing cells both varied from the early myeloid progenitor phenotype of the parental cells and gave rise to a small number of large to giant adherent cells that expressed macrophage (alpha-naphthyl acetate) esterase and neutrophil (naphtol-AS-D-chloroacetate) esterase, were highly phagocytic and phenotypically resembled histiocytes. Thus, WTKit activated by SCF and V816Kit were able to induce differentiation in a proportion of Myb-transformed myeloid cells. The factor independent V816Kit cells, unlike the parental and WTKit expressing cells, were shown to produce tumors of highly mitotic, invasive cells at various stages of differentiation in syngeneic mice. These results imply that constitutively activated Kit can promote the development of differentiated myeloid tumors and that its oncogenic effects are not restricted to lineages (mast cell and B-cell acute lymphoblastic leukemia), which have been reported previously. Furthermore, the mixed populations of cells in culture and in the tumors phenotypically resembled the leukemic cells from patients with monocytic leukemia with histiocytic differentiation (acute myeloid leukemia-M5c), a newly proposed subtype of myeloid leukemia. (C) 1997 by The American Society of Hematology.

Paternal and maternal ages at conception and risk of bipolar affective disorder in their offspring

Background. A consistent association between paternal age and their offspring`s risk of schizophrenia has been observed, with no independent association with maternal age. The relationship of paternal and maternal ages with risk of bipolar affective disorders (BPAD) in the offspring is less clear. The present study aimed at testing the hypothesis that paternal age is associated with their offspring`s risk of BPAD, whereas maternal age is not. Method. This population-based cohort study was conducted with individuals born in Sweden during 1973-1980 and still resident there at age 16 years. Outcome was first hospital admission with a diagnosis of BPAD. Hazard ratios (HRs) were calculated using Cox`s proportional hazard regression. Results. After adjustment for all potential confounding variables except maternal age, the HR for risk of BPAD for each 10-year increase in paternal age was 1.28 [95% confidence interval (Cl) 1.11-1.48], but this fell to 1.20 (95% CI 0.97-1.48) after adjusting for maternal age. A similar result was found for maternal age and risk of BPAD [HR 1.30 (95% CI 1.08-1.56) before adjustment for paternal age, HR 1.12 (95% Cl 0.86-1.45) after adjustment]. The HR associated with having either parent aged 30 years or over was 1.26 (95% CI 1.01-1.57) and it was 1.45 (95%, CI 1.16-1.81) if both parents were >30 years. Conclusions. Unlike schizophrenia, the risk of BPAD seems to be associated with both paternal and maternal ages.