A latitudinal gradient in thermal transgenerational plasticity and a test of theory.

Transgenerational plasticity (TGP) occurs when phenotypes are shaped by the environment in both the current and preceding generations. Transgenerational responses to rainfall, CO2 and temperature suggest that TGP may play an important role in how species cope with climate change. However, little is known about how TGP will evolve as climate change continues. Here, we provide a quantitative test of the hypothesis that the predictability of the environment influences the magnitude of the transgenerational response. To do so, we take advantage of the latitudinal decrease in the predictability of temperatures in near shore waters along the US East Coast. Using sheepshead minnows (Cyprinodon variegatus) from South Carolina, Maryland, and Connecticut, we found the first evidence for a latitudinal gradient in thermal TGP. Moreover, the degree of TGP in these populations depends linearly on the decorrelation time for temperature, providing support for the hypothesis that thermal predictability drives the evolution of these traits.

Using seasonal genomic changes to understand historical adaptation to new environments: Parallel selection on stickleback in highly-variable estuaries.

Parallel evolution is considered strong evidence for natural selection. However, few studies have investigated the process of parallel selection as it plays out in real time. The common approach is to study historical signatures of selection in populations already well adapted to different environments. Here, to document selection under natural conditions, we study six populations of threespine stickleback (Gasterosteus aculeatus) inhabiting bar-built estuaries that undergo seasonal cycles of environmental changes. Estuaries are periodically isolated from the ocean due to sandbar formation during dry summer months, with concurrent environmental shifts that resemble the long-term changes associated with postglacial colonization of freshwater habitats by marine populations. We used pooled whole-genome sequencing to track seasonal allele frequency changes in six of these populations and search for signatures of natural selection. We found consistent changes in allele frequency across estuaries, suggesting a potential role for parallel selection. Functional enrichment among candidate genes included transmembrane ion transport and calcium binding, which are important for osmoregulation and ion balance. The genomic changes that occur in threespine stickleback from bar-built estuaries could provide a glimpse into the early stages of adaptation that have occurred in many historical marine to freshwater transitions.

Adaptation in temporally variable environments: stickleback armor in periodically breaching bar-built estuaries.

The evolutionary consequences of temporal variation in selection remain hotly debated. We explored these consequences by studying threespine stickleback in a set of bar-built estuaries along the central California coast. In most years, heavy rains induce water flow strong enough to break through isolating sand bars, connecting streams to the ocean. New sand bars typically re-form within a few weeks or months, thereby re-isolating populations within the estuaries. These breaching events cause severe and often extremely rapid changes in abiotic and biotic conditions, including shifts in predator abundance. We investigated whether this strong temporal environmental variation can maintain within-population variation while eroding adaptive divergence among populations that would be caused by spatial variation in selection. We used neutral genetic markers to explore population structure and then analysed how stickleback armor traits, the associated genes Eda and Pitx1 and elemental composition (%P) varies within and among populations. Despite strong gene flow, we detected evidence for divergence in stickleback defensive traits and Eda genotypes associated with predation regime. However, this among-population variation was lower than that observed among other stickleback populations exposed to divergent predator regimes. In addition, within-population variation was very high as compared to populations from environmentally stable locations. Elemental composition was strongly associated with armor traits, Eda genotype and the presence of predators, thus suggesting that spatiotemporal variation in armor traits generates corresponding variation in elemental phenotypes. We conclude that gene flow, and especially temporal environmental variation, can maintain high levels of within-population variation while reducing, but not eliminating, among-population variation driven by spatial environmental variation.

Habitat association in populations on landscapes with continuous-valued heterogeneous habitat quality.

We explore a spatially implicit patch-occupancy model of a population on a landscape with continuous-valued heterogeneous habitat quality, primarily considering the case where the habitat quality of a site affects the mortality rate but not the fecundity of individuals at that site. Two analytical approaches to the model are constructed, by summing over the sites in the landscape and by integrating over the range of habitat quality. We obtain results relating the equilibrium population density and all moments of the probability distribution of the habitat quality of occupied sites, and relating the probability distributions of total habitat quality and occupied habitat quality. Special cases are considered for landscapes where habitat quality has either a uniform or a linear probability density function. For these cases, we demonstrate habitat association, where the quality of occupied sites is higher than the overall mean quality of all sites; the discrepancy between the two is reduced at larger population densities. The variance of the quality of occupied sites may be greater or less than the overall variance of habitat quality, depending on the distribution of habitat quality across the landscape. Increasing the variance of habitat quality is also shown to increase the ability of a population to persist on a landscape.

White matter predictors of cognitive functioning in older adults.

Few studies have applied multiple imaging modalities to examine cognitive correlates of white matter. We examined the utility of T2-weighted magnetic resonance imaging (MRI) -derived white matter hyperintensities (WMH) and diffusion tensor imaging-derived fractional anisotropy (FA) to predict cognitive functioning among older adults. Quantitative MRI and neuropsychological evaluations were performed in 112 older participants from an ongoing study of the genetics of Alzheimer's disease (AD) in African Americans. Regional WMH volumes and FA were measured in multiple regions of interest. We examined the association of regional WMH and an FA summary score with cognitive test performance. Differences in WMH and FA were compared across diagnostic groups (i.e., normal controls, mild cognitive impairment, and probable AD). Increased WMH volume in frontal lobes was associated with poorer delayed memory performance. FA did not emerge as a significant predictor of cognition. White matter hyperintensity volume in the frontal and parietal lobes was increased in MCI participants and more so in AD patients relative to controls. These results highlight the importance of regionally distributed small vessel cerebrovascular disease in memory performance and AD among African American older adults. White matter microstructural changes, quantified with diffusion tensor imaging, appear to play a lesser role in our sample.

Age and Graphomotor Decision Making Assessed with the Digital Clock Drawing Test: The Framingham Heart Study.

BACKGROUND: Digital Clock Drawing Test (dCDT) technology enables the examination of detailed neurocognitive behavior as behavior unfolds in real time; a capability that cannot be obtained using a traditional pen and paper testing format. OBJECTIVE: Parameters obtained from the dCDT were used to investigate neurocognitive constructs related to higher-order neurocognitive decision making and information processing speed. The current research sought to determine the effect of age as related to combined motor and non-motor components of drawing, and higher-order decision making latencies. METHODS: A large group of stroke- and dementia- free Framingham Heart Study participants were administered the dCDT to command and copy with hands set for "10 after 11". Six age groups (age range 28-98) were constructed. RESULTS: Differences between age groups were found for total time to completion, total pen stroke count, and higher-order decision making latencies in both command and copy test conditions. CONCLUSION: Longer age-related decision making latencies may reflect a greater need for working memory and increased self-monitoring in older subjects. These latency measures have potential to serve as neurocognitive biomarkers of Alzheimer's disease and other insidious neurodegenerative disorders.

White matter hyperintensities and cerebral amyloidosis: necessary and sufficient for clinical expression of Alzheimer disease?

IMPORTANCE: Current hypothetical models emphasize the importance of ß-amyloid in Alzheimer disease (AD) pathogenesis, although amyloid alone is not sufficient to account for the dementia syndrome. The impact of small-vessel cerebrovascular disease, visualized as white matter hyperintensities (WMHs) on magnetic resonance imaging scans, may be a key factor that contributes independently to AD presentation. OBJECTIVE: To determine the impact of WMHs and Pittsburgh Compound B (PIB) positron-emission tomography-derived amyloid positivity on the clinical expression of AD. DESIGN: Baseline PIB-positron-emission tomography values were downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Total WMH volume was derived on accompanying structural magnetic resonance imaging data. We examined whether PIB positivity and total WMHs predicted diagnostic classification of patients with AD (n = 20) and control subjects (n = 21). A second analysis determined whether WMHs discriminated between those with and without the clinical diagnosis of AD among those who were classified as PIB positive (n = 28). A third analysis examined whether WMHs, in addition to PIB status, could be used to predict future risk for AD among subjects with mild cognitive impairment (n = 59). SETTING: The Alzheimer's Disease Neuroimaging Initiative public database. PARTICIPANTS: The study involved data from 21 normal control subjects, 59 subjects with mild cognitive impairment, and 20 participants with clinically defined AD from the Alzheimer Disease's Neuroimaging Initiative database. MAIN OUTCOME MEASURES: Clinical AD diagnosis and WMH volume. RESULTS: Pittsburgh Compound B positivity and increased total WMH volume independently predicted AD diagnosis. Among PIB-positive subjects, those diagnosed as having AD had greater WMH volume than normal control subjects. Among subjects with mild cognitive impairment, both WMH and PIB status at baseline conferred risk for future diagnosis of AD. CONCLUSIONS AND RELEVANCE: White matter hyperintensities contribute to the presentation of AD and, in the context of significant amyloid deposition, may provide a second hit necessary for the clinical manifestation of the disease. As risk factors for the development of WMHs are modifiable, these findings suggest intervention and prevention strategies for the clinical syndrome of AD.

Testing the white matter retrogenesis hypothesis of cognitive aging.

The retrogenesis hypothesis postulates that late-myelinated white matter fibers are most vulnerable to age- and disease-related degeneration, which in turn mediate cognitive decline. While recent evidence supports this hypothesis in the context of Alzheimer's disease, it has not been tested systematically in normal cognitive aging. In the current study, we examined the retrogenesis hypothesis in a group (n = 282) of cognitively normal individuals, ranging in age from 7 to 87 years, from the Brain Resource International Database. Participants were evaluated with a comprehensive neuropsychological battery and were imaged with diffusion tensor imaging. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (DA), measures of white matter coherence, were computed in 2 prototypical early-myelinated fiber tracts (posterior limb of the internal capsule, cerebral peduncles) and 2 prototypical late-myelinated fiber tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus) chosen to parallel previous studies; mean summary values were also computed for other early- and late-myelinated fiber tracts. We examined age-associated differences in FA, RD, and DA in the developmental trajectory (ages 7-30 years) and degenerative trajectory (ages 31-87 years), and tested whether the measures of white matter coherence mediated age-related cognitive decline in the older group. FA and DA values were greater for early-myelinated fibers than for late-myelinated fibers, and RD values were lower for early-myelinated than late-myelinated fibers. There were age-associated differences in FA, RD, and DA across early- and late-myelinated fiber tracts in the younger group, but the magnitude of differences did not vary as a function of early or late myelinating status. FA and RD in most fiber tracts showed reliable age-associated differences in the older age group, but the magnitudes were greatest for the late-myelinated tract summary measure, inferior longitudinal fasciculus (late fiber tract), and cerebral peduncles (early fiber tract). Finally, FA in the inferior longitudinal fasciculus and cerebral peduncles and RD in the cerebral peduncles mediated age-associated differences in an executive functioning factor. Taken together, the findings highlight the importance of white matter coherence in cognitive aging and provide some, but not complete, support for the white matter retrogenesis hypothesis in normal cognitive aging.

Eco-evolutionary trophic dynamics: loss of top predators drives trophic evolution and ecology of prey.

Ecosystems are being altered on a global scale by the extirpation of top predators. The ecological effects of predator removal have been investigated widely; however, predator removal can also change natural selection acting on prey, resulting in contemporary evolution. Here we tested the role of predator removal on the contemporary evolution of trophic traits in prey. We utilized a historical introduction experiment where Trinidadian guppies (Poecilia reticulata) were relocated from a site with predatory fishes to a site lacking predators. To assess the trophic consequences of predator release, we linked individual morphology (cranial, jaw, and body) to foraging performance. Our results show that predator release caused an increase in guppy density and a "sharpening" of guppy trophic traits, which enhanced food consumption rates. Predator release appears to have shifted natural selection away from predator escape ability and towards resource acquisition ability. Related diet and mesocosm studies suggest that this shift enhances the impact of guppies on lower trophic levels in a fashion nuanced by the omnivorous feeding ecology of the species. We conclude that extirpation of top predators may commonly select for enhanced feeding performance in prey, with important cascading consequences for communities and ecosystems.

Analysis of cell-cycle specific localization of the Rdi1p RhoGDI and the structural determinants required for Cdc42p membrane localization and clustering at sites of polarized growth.

The Cdc42p GTPase regulates multiple signal transduction pathways through its interactions with downstream effectors. Specific functional domains within Cdc42p are required for guanine-nucleotide binding, interactions with downstream effectors, and membrane localization. However, little is known about how Cdc42p is clustered at polarized growth sites or is extracted from membranes by Rho guanine-nucleotide dissociation inhibitors (RhoGDIs) at specific times in the cell cycle. To address these points, localization studies were performed in Saccharomyces cerevisiae using green fluorescent protein (GFP)-tagged Cdc42p and the RhoGDI Rdi1p. GFP-Rdi1p localized to polarized growth sites at specific times of the cell cycle but not to other sites of Cdc42p localization. Overexpression of Rdi1p led to loss of GFP-Cdc42p from internal and plasma membranes. This effect was mediated through the Cdc42p Rho-insert domain, which was also implicated in interactions with the Bni1p scaffold protein. These data suggested that Rdi1p functions in cell cycle-specific Cdc42p membrane detachment. Additional genetic and time-lapse microscopy analyses implicated nucleotide binding in the clustering of Cdc42p. Taken together, these results provide insight into the complicated nature of the relationships between Cdc42p localization, nucleotide binding, and protein-protein interactions.