Thinking and doing: the effects of dopamine and oxytocin genes and executive function on mothering behaviours

Animal and human studies suggest that initial expression of maternal behaviour depends on oxytocin and dopamine systems. However, the mechanism by which these systems affect parenting behaviours and the timing of these effects are not well understood. This article explores the role of mothers' executive function in mediating the relation between oxytocin and dopamine gene variants and maternal responsiveness at 48 months post‐partum. Participants (n = 157) were mothers recruited in the Maternal Adversity, Vulnerability and Neurodevelopment Study, which assesses longitudinally two cohorts of mothers and children in Canada. We examined single nucleotide polymorphisms (SNPs) related to the dopamine and oxytocin systems (DRD1 rs686, DRD1 rs265976, OXTR rs237885 and OXTR rs2254298), assessed mothers' decision‐making at 48 months using the Cambridge Neurological Automated Testing Battery (CANTAB) and evaluated maternal responsiveness from videotaped interactions during the Etch‐A‐Sketch co‐operation task. Mediation analyses showed that OXTR rs2254298 A‐carriers had an indirect effect on positive parenting which was mediated by mothers' performance on decision‐making task (estimate = 0.115, P < 0.005), while OXTR rs2254298 A‐carriers had both direct and indirect effects on physically controlling parenting, also mediated through enhanced performance on decision‐making (estimate = ?0.059, P < 0.005). Dopamine SNPs were not associated with any measure of executive function or parenting (all P > 0.05). While oxytocin has previously been associated with only the early onset of maternal behaviour, we show that an OXTR polymorphism is involved in maternal behaviour at 48 months post‐partum through mothers' executive function. This research highlights the importance of the oxytocin system to maternal parenting beyond infancy.     

Effects of Maternal Obstructive Sleep Apnoea on Fetal Growth: A Prospective Cohort Study

Objective

The objective of this study is to determine whether obstructive sleep apnea (OSA) is associated with reduced fetal growth, and whether nocturnal oxygen desaturation precipitates acute fetal heart rate changes.

Study Design

We performed a prospective observational study, screening 371 women in the second trimester for OSA symptoms. 41 subsequently underwent overnight sleep studies to diagnose OSA. Third trimester fetal growth was assessed using ultrasound. Fetal heart rate monitoring accompanied the sleep study. Cord blood was taken at delivery, to measure key regulators of fetal growth.

Results

Of 371 women screened, 108 (29%) were high risk for OSA. 26 high risk and 15 low risk women completed the longitudinal study; 14 had confirmed OSA (cases), and 27 were controls. The median (interquartile range) respiratory disturbance index (number of apnoeas, hypopnoeas or respiratory related arousals/hour of sleep) was 7.9 (6.1–13.8) for cases and 2.2 (1.3–3.5) for controls (p<0.001). Impaired fetal growth was observed in 43% (6/14) of cases, vs 11% (3/27) of controls (RR 2.67; 1.25–5.7; p = 0.04). Using logistic regression, only OSA (OR 6; 1.2–29.7, p = 0.03) and body mass index (OR 2.52; 1.09–5.80, p = 0.03) were significantly associated with impaired fetal growth. After adjusting for body mass index on multivariate analysis, the association between OSA and impaired fetal growth was not appreciably altered (OR 5.3; 0.93–30.34, p = 0.06), although just failed to achieve statistical significance. Prolonged fetal heart rate decelerations accompanied nocturnal oxygen desaturation in one fetus, subsequently found to be severely growth restricted. Fetal growth regulators showed changes in the expected direction- with IGF-1 lower, and IGFBP-1 and IGFBP-2 higher- in the cord blood of infants of cases vs controls, although were not significantly different.

Conclusion

OSA may be associated with reduced fetal growth in late pregnancy. Further evaluation is warranted to establish whether OSA may be an important contributor to adverse perinatal outcome, including stillbirth.     

Valproic acid induces extracellular signal-regulated kinase 1/2 activation and inhibits apoptosis in endothelial cells

The histone deacetylase (HDAC) inhibitor valproic acid (VPA) was recently shown to inhibit angiogenesis, but displays no toxicity in endothelial cells. Here, we demonstrate that VPA increases extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation in human umbilical vein endothelial cells (HUVEC). The investigation of structurally modified VPA derivatives revealed that the induction of ERK 1/2 phosphorylation is not correlated to HDAC inhibition. PD98059, a pharmacological inhibitor of the mitogen-activated protein kinase kinase 1/2, prevented the VPA-induced ERK 1/2 phosphorylation. In endothelial cells, ERK 1/2 phosphorylation is known to promote cell survival and angiogenesis. Our results showed that VPA-induced ERK 1/2 phosphorylation in turn causes phosphorylation of the antiapoptotic protein Bcl-2 and inhibits serum starvation-induced HUVEC apoptosis and cytochrome c release from the mitochondria. Moreover, the combination of VPA with PD98059 synergistically inhibited angiogenesis in vitro and in vivo.     

EVOLUTION OF ADULT FEMALE LIFE HISTORY AND MORPHOLOGY IN A PACIFIC SALMON (COHO: ONCORHYNCHUS KISUTCH)

Female competition on the spawning grounds can generate strong natural selection on female coho salmon (Oncorhynchus kisutch). We examined the morphology and investment into egg production of 13 wild and five hatchery populations. For each population, the degrees of breeding competition and migration arduousness were quantified. The results support the importance of breeding competition in the evolution of female morphology and life history. Female secondary sexual characters, including body coloration and length of kype (an extension of the upper jaw used for fighting), increase significantly with degree of breeding competition among populations. In contrast, egg size and female investment into egg production tend to decrease as competition increases, probably as a result of life-history trade-offs. The difficulty of migration to the spawning grounds also molds female morphology and life history. Salmon become more streamlined with increasing migration arduousness, and the biomass of eggs produced appears to decline. In hatcheries, where breeding competition is relaxed, characters associated with breeding competition and spawning performance are reduced. In contrast, egg size is increased. These results indicate that the morphology and life history of adult female salmon respond evolutionarily to local selection pressures, including both the biotic demands of breeding competition and the abiotic demands of migration.     

Novel structural insights into rotavirus recognition of ganglioside glycan receptors

Rotaviruses ubiquitously infect children under the age of 5, being responsible for more than half a million diarrhoeal deaths each year worldwide. Host cell oligosaccharides containing sialic acid(s) are critical for attachment by rotaviruses. However, to date, no detailed three-dimensional atomic model showing the exact rotavirus interactions with these glycoconjugate receptors has been reported. Here, we present the first crystallographic structures of the rotavirus carbohydrate-recognizing protein VP8^? in complex with ganglioside G_M3 glycans. In combination with assessment of the inhibition of rotavirus infectivity by N-acetyl and N-glycolyl forms of this ganglioside, our results reveal key details of rotavirus-ganglioside G_M3 glycan recognition. In addition, they show a direct correlation between the carbohydrate specificities exhibited by VP8^? from porcine and by monkey rotaviruses and the respective infectious virus particles. These novel results also indicate the potential binding interactions of rotavirus VP8^? with other sialic acid-containing gangliosides.     

Death and the Oldest Old: Attitudes and Preferences for End-of-Life Care - Qualitative Research within a Population-Based Cohort Study

IntroductionIncreasing longevity means more people will be dying in very old age, but little is known about the preferences of the ‘oldest old’ regarding their care at the end of life.AimsTo understand very old people’s preferences regarding care towards the end of life and attitudes towards dying, to inform policy and practice.MethodsQualitative data collection for n = 42 population-based cohort study participants aged 95–101 (88% women, 42% in long-term-care): topic-guided interviews with n = 33 participants and n = 39 proxy informants, most with both (n = 30: 4 jointly + separate interviews for 26 dyads).ResultsDeath was a part of life: these very old people mainly live day-to-day. Most were ready to die, reflecting their concerns regarding quality of life, being a nuisance, having nothing to live for and having lived long enough. Contrasting views were rare exceptions but voiced firmly. Most were not worried about death itself, but concerned more about the dying process and impacts on those left behind; a peaceful and pain-free death was a common ideal. Attitudes ranged from not wanting to think about death, through accepting its inevitable approach to longing for its release. Preferring to be made comfortable rather than have life-saving treatment if seriously ill, and wishing to avoid hospital, were commonly expressed views. There was little or no future planning, some consciously choosing not to. Uncertainty hampered end-of-life planning even when death was expected soon. Some stressed circumstances, such as severe dependency and others’ likely decision-making roles, would influence choices. Carers found these issues harder to raise but felt they would know their older relatives’ preferences, usually palliative care, although we found two discrepant views.ConclusionsThis study’s rare data show ≥95-year-olds are willing to discuss dying and end-of-life care but seldom do. Formal documentation of wishes is extremely rare and may not be welcome. Although being “ready to die” and preferring a palliative approach predominated, these preferences cannot be assumed.     

Surface respreading after collapse of monolayers containing major lipids of pulmonary surfactant

Isotherms have been obtained near 37 degrees C for a series of repetitive compressions and expansions of monolayers that contain major components of lung surfactant. The minimum surface tension or maximum surface pressure which could be achieved under conditions of dynamic compression, and the rate of return of lipid from excluded phase to the monolayers were measured. Monolayers of pure 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), or of DPPC plus 10 or 30 mol% of the calcium salt of 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (POPG) (POPG-Ca) achieved very high surface pressures or low surface tensions (near 0 mN m-1), but they showed no return of material from the collapse phases under the test conditions. Monolayers of POPG-Ca alone collapsed at relatively low surface pressures (high surface tensions), but showed good return of material from the collapse phase into the monolayer. Monolayers containing more complex mixtures of lipids (DPPC, phosphatidylglycerol (PG), unsaturated phosphatidylcholine (PC), cholesterol (chol] in ratios similar to those found in surfactant achieved minimum surface tensions intermediate between those of monolayers with less complex compositions. These more complex mixtures showed a better rate of return of lipids from the collapse phases to the monolayer than did simple DPPC-POPG mixtures. 31P-NMR and differential scanning calorimetric investigations of the mixture DPPC/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)/POP G/DPPG/chol (10:4:2:1:3) showed that in the bulk phase at 37 degrees C, it was in bilayers in the liquid-crystalline state.     

Occurrence of an inhibitor of lactic Acid bacteria in green olives

Green olives were found to contain an inhibitor(s) of several species of lactic acid bacteria usually associated with the Spanish-type brined olive fermentation. The inhibitor was demonstrated by the presence of inhibition zones surrounding tissue which had been cut from frozen olives and implanted in a seeded nutritive agar medium. Relative potencies of aqueous extracts of frozen olives were determined by a paper disc assay method. The Mission variety of olive contained the most inhibitor, and the Manzanillo and Ascolano, about 50 and 40% as much as the Mission variety, respectively. Sevillano and Barouni varieties contained comparatively little inhibitor. Effects of the inhibitor on growth rates of lactic acid bacteria were determined by adding various amounts of a concentrated aqueous extract of olives to a nutritive broth medium contained in screw-capped tubes. Of the four species of lactic acid bacteria tested, Leuconostoc mesenteroides was the most sensitive, and Lactobacillus plantarum was the least sensitive; Pediococcus cerevisiae and Lactobacillus brevis were intermediate in sensitivity. Extracts possessed a bactericidal property, as evidenced by their effect on L. mesenteroides. Sodium chloride, especially at concentrations of about 5% and higher, greatly increased the effectiveness of the inhibitor. The inhibitor was ethyl alcohol-soluble and was stable when heated at 100 C in aqueous solution. Potencies of extracts were reduced greatly by adjustment to pH 10, but no appreciable effect was noted by adjustment to pH 0.8.