Measuring inputs to a common function: The case of Dlx5 and Dlx6.

Physically linked Dlx5 and Dlx6 paralogs are co-expressed in vertebrates and various combinations of null alleles in mice demonstrate not only functional redundancy between the paralogous factors but a similar quantitative contribution to craniofacial functions during development. While it is not possible to rule out that the bigene pair contributes some paralog-specific functions it is clear that, for many functions in the head, Dlx5 and Dlx6 are interchangeable. To assess the relative quantitative contribution made by each paralog to bigene function, we have made comparisons of the expression of Dlx5 and Dlx6 in chick embryos and quantitated the transcriptional properties of the encoded proteins in a variety of regulatory and cellular contexts. Our data indicate that the transcriptional activities of both Dlx5 and Dlx6 are very much context dependent; isolated domains fused to a heterologous DNA binding domain have little intrinsic activity, while individual domains are more active when contiguous with their own homeodomain. We find Dlx5 and Dlx6 to be quantitatively indistinguishable on a variety of natural cis-regulatory sequences in a heterologous cellular context but observed quantitatively different transcriptional outputs in cells that normally express these genes, suggesting differential interactions with co-evolved co-activators.

Prospective study of Dietary Approaches to Stop Hypertension- and Mediterranean-style dietary patterns and age-related cognitive change: the Cache County Study on Memory, Health and Aging.

BACKGROUND: Healthy dietary patterns may protect against age-related cognitive decline, but results of studies have been inconsistent. OBJECTIVE: We examined associations between Dietary Approaches to Stop Hypertension (DASH)- and Mediterranean-style dietary patterns and age-related cognitive change in a prospective, population-based study. DESIGN: Participants included 3831 men and women ≥65 y of age who were residents of Cache County, UT, in 1995. Cognitive function was assessed by using the Modified Mini-Mental State Examination (3MS) ≤4 times over 11 y. Diet-adherence scores were computed by summing across the energy-adjusted rank-order of individual food and nutrient components and categorizing participants into quintiles of the distribution of the diet accordance score. Mixed-effects repeated-measures models were used to examine 3MS scores over time across increasing quintiles of dietary accordance scores and individual food components that comprised each score. RESULTS: The range of rank-order DASH and Mediterranean diet scores was 1661-25,596 and 2407-26,947, respectively. Higher DASH and Mediterranean diet scores were associated with higher average 3MS scores. People in quintile 5 of DASH averaged 0.97 points higher than those in quintile 1 (P = 0.001). The corresponding difference for Mediterranean quintiles was 0.94 (P = 0.001). These differences were consistent over 11 y. Higher intakes of whole grains and nuts and legumes were also associated with higher average 3MS scores [mean quintile 5 compared with 1 differences: 1.19 (P < 0.001), 1.22 (P < 0.001), respectively]. CONCLUSIONS: Higher levels of accordance with both the DASH and Mediterranean dietary patterns were associated with consistently higher levels of cognitive function in elderly men and women over an 11-y period. Whole grains and nuts and legumes were positively associated with higher cognitive functions and may be core neuroprotective foods common to various healthy plant-centered diets around the globe.