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Coronary artery disease is the most common cause of death globally and is linked to a number of risk factors including serum low density lipoprotein, high density lipoprotein, triglycerides and lipoprotein(a). Recently two proteins, angiopoietin-like protein 3 and 4, have emerged from genetic studies as being factors that significantly modulate plasma triglyceride levels and coronary artery disease. The exact function and mechanism of action of both proteins remains to be elucidated, however, mutations in these proteins results in up to 34% reduction in coronary artery disease and inhibition of function results in reduced plasma triglyceride levels. Here we report the crystal structures of the fibrinogen-like domains of both proteins. These structures offer new insights into the reported loss of function mutations, the mechanisms of action of the proteins and open up the possibility for the rational design of low molecular weight inhibitors for intervention in coronary artery disease.
Purpose
To test whether the negative relationship between perceived stress and quality of life (Hypothesis 1) can be buffered by perceived social support in patients with dementia as well as in caregivers individually (Hypothesis 2: actor effects) and across partners (Hypothesis 3: partner effects and actor-partner effects).
Method
A total of 108 couples (N = 216 individuals) comprised of one individual with early-stage dementia and one caregiving partner were assessed at baseline and one month apart. Moderation effects were investigated by applying linear mixed models and actor-partner interdependence models.
Results
Although the stress-quality of life association was more pronounced in caregivers (beta = -.63, p<.001) compared to patients (beta= -.31, p<.001), this association was equally moderated by social support in patients (beta = .14, p<.05) and in the caregivers (beta =.13, p<.05). From one partner to his or her counterpart, the partner buffering and actor-partner-buffering effect were not present.
Conclusion
The stress-buffering effect has been replicated in individuals with dementia and caregivers but not across partners. Interventions to improve quality of life through perceived social support should not only focus on caregivers, but should incorporate both partners.
Genetic and environmental factors both contribute to cognitive test performance. A substantial increase in average intelligence test results in the second half of the previous century within one generation is unlikely to be explained by genetic changes. One possible explanation for the strong malleability of cognitive performance measure is that environmental factors modify gene expression via epigenetic mechanisms. Epigenetic factors may help to understand the recent observations of an association between dopamine-dependent encoding of reward prediction errors and cognitive capacity, which was modulated by adverse life events. The possible manifestation of malleable biomarkers contributing to variance in cognitive test performance, and thus possibly contributing to the "missing heritability" between estimates from twin studies and variance explained by genetic markers, is still unclear. Here we show in 1475 healthy adolescents from the IMaging and GENetics (IMAGEN) sample that general IQ (gIQ) is associated with (1) polygenic scores for intelligence, (2) epigenetic modification of DRD2 gene, (3) gray matter density in striatum, and (4) functional striatal activation elicited by temporarily surprising reward-predicting cues. Comparing the relative importance for the prediction of gIQ in an overlapping subsample, our results demonstrate neurobiological correlates of the malleability of gIQ and point to equal importance of genetic variance, epigenetic modification of DRD2 receptor gene, as well as functional striatal activation, known to influence dopamine neurotransmission. Peripheral epigenetic markers are in need of confirmation in the central nervous system and should be tested in longitudinal settings specifically assessing individual and environmental factors that modify epigenetic structure.