Genome-Wide Analysis in Reveals the Genetic Basis of Variation in Age-Specific Physical Performance and Response to ACE Inhibition.

Despite impressive results in restoring physical performance in rodent models, treatment with renin-angiotensin system (RAS) inhibitors, such as Lisinopril, have highly mixed results in humans, likely, in part, due to genetic variation in human populations. To date, the genetic determinants of responses to drugs, such as RAS inhibitors, remain unknown. Given the complexity of the relationship between physical traits and genetic background, genomic studies which predict genotype- and age-specific responses to drug treatments in humans or vertebrate animals are difficult.

Next Steps in Integrative Biology: Mapping Interactive Processes Across Levels of Biological Organization.

Emergent biological processes result from complex interactions within and across levels of biological organization, ranging from molecular to environmental dynamics. Powerful theories, database tools, and modeling methods have been designed to characterize network connections within levels, such as those among genes, proteins, biochemicals, cells, organisms, and species. Here, we propose that developing integrative models of organismal function in complex environments can be facilitated by taking advantage of these methods to identify key nodes of communication across levels of organization.

Ancestral ecological regime shapes reaction to food limitation in the Least Killifish, .

Populations with different densities often show genetically based differences in life histories. The divergent life histories could be driven by several agents of selection, one of which is variation in per-capita food levels. Its relationship with population density is complex, as it depends on overall food availability, individual metabolic demand, and food-independent factors potentially affecting density, such as predation intensity.

DROP: Molecular voucher database for identification of Drosophila parasitoids.

Molecular identification is increasingly used to speed up biodiversity surveys and laboratory experiments. However, many groups of organisms cannot be reliably identified using standard databases such as GenBank or BOLD due to lack of sequenced voucher specimens identified by experts. Sometimes a large number of sequences are available, but with too many errors to allow identification.

Assessing the Age-Specific Phagocytic Ability of Adult Drosophila melanogaster Hemocytes using an In Vivo Phagocytosis Assay.

Phagocytosis is an essential function of the innate immune response. This process is carried out by phagocytic hemocytes whose primary function is to recognize a wide range of particles and destroy microbial pathogens. As organisms age, this process begins to decline, yet little is known about the underlying mechanisms or the genetic basis of immunosenescence.

Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster.

Physical resiliency declines with age and comorbid conditions. In humans, angiotensin-converting enzyme (ACE) has been associated with attenuation of the decline in physical performance with age. ACE-inhibitor compounds, commonly prescribed for hypertension, often have beneficial effects on physical performance however the generality of these effects are unclear.

Geographic and Seasonal Variation in Species Diversity and Community Composition of Frugivorous Drosophila (Diptera: Drosophilidae) and their Leptopilina (Hymenoptera: Figitidae) Parasitoids.

Many studies have investigated species diversity patterns across space and time, but few have explored patterns of coexistence of tightly interacting species. We documented species diversity patterns in a host-parasitoid system across broad geographic location and seasons. We calculated species diversity (H and eH   ') and compared the relationship between community similarity and geographic distances of frugivorous Drosophila host (Diptera: Drosophilidae) and Leptopilina parasitoid (Hymenoptera: Figitidae) communities across Eastern North America, from New Hampshire to Florida, at two time points during the breeding season.

Knockdown expression of Syndecan in the fat body impacts nutrient metabolism and the organismal response to environmental stresses in Drosophila melanogaster.

The heparan sulfate proteoglycan syndecans are transmembrane proteins involved in multiple physiological processes, including cell-matrix adhesion and inflammation. Recent evidence from model systems and humans suggest that syndecans have a role in energy balance and nutrient metabolism regulation. However, much remains to be learned about the mechanisms through which syndecans influence these phenotypes.

Development and Assessment of Modules to Integrate Quantitative Skills in Introductory Biology Courses.

Redesigning undergraduate biology courses to integrate quantitative reasoning and skill development is critical to prepare students for careers in modern medicine and scientific research. In this paper, we report on the development, implementation, and assessment of stand-alone modules that integrate quantitative reasoning into introductory biology courses. Modules are designed to improve skills in quantitative numeracy, interpreting data sets using visual tools, and making inferences about biological phenomena using mathematical/statistical models.

Variable light environments induce plastic spectral tuning by regional opsin coexpression in the African cichlid fish, Metriaclima zebra.

Critical behaviours such as predation and mate choice often depend on vision. Visual systems are sensitive to the spectrum of light in their environment, which can vary extensively both within and among habitats. Evolutionary changes in spectral sensitivity contribute to divergence and speciation.

Genome-wide analysis in Drosophila reveals age-specific effects of SNPs on fitness traits.

Most organisms exhibit senescence; a decline in physiological function with age. In nature, rates of senescence vary extensively among individuals and this variation has a significant genetic component; however, we know little about the genes underlying senescence. Here we show the first evidence that individual alleles influence fecundity in an age-specific manner and so the genetic basis of natural variation in fecundity changes dramatically with age.

Phagocytic ability declines with age in adult Drosophila hemocytes.

Most multicellular organisms show a physiological decline in immune function with age. However, little is known about the mechanisms underlying these changes. We examined Drosophila melanogaster, an important model for identifying genes affecting innate immunity and senescence, to explore the role of phagocytosis in age-related immune dysfunction.

Evolution in population parameters: density-dependent selection or density-dependent fitness?

Density-dependent selection is one of earliest topics of joint interest to both ecologists and evolutionary biologists and thus occupies an important position in the histories of these disciplines. This joint interest is driven by the fact that density-dependent selection is the simplest form of feedback between an ecological effect of an organism's own making (crowding due to sustained population growth) and the selective response to the resulting conditions. This makes density-dependent selection perhaps the simplest process through which we see the full reciprocity between ecology and evolution.

The adaptive significance of population differentiation in offspring size of the least killifish, Heterandria formosa.

We tested the hypothesis that density-dependent competition influences the evolution of offspring size. We studied two populations of the least killifish (Heterandria formosa) that differ dramatically in population density; these populations are genetically differentiated for offspring size, and females from both populations produce larger offspring when they experience higher social densities. To look at the influences of population of origin and relative body size on competitive ability, we held females from the high-density population at two different densities to create large and small offspring with the same genetic background.

Defense traits of larval Drosophila melanogaster exhibit genetically based trade-offs against different species of parasitoids.

Populations of Drosophila melanogaster face significant mortality risks from parasitoid wasps that use species-specific strategies to locate and survive in hosts. We tested the hypothesis that parasitoids with different strategies select for alternative host defense characteristics and in doing so contribute to the maintenance of fitness variation and produce trade-offs among traits. We characterized defense traits of Drosophila when exposed to parasitoids with different host searching behaviors (Aphaereta sp.

Genomic basis of aging and life-history evolution in Drosophila melanogaster.

Natural diversity in aging and other life-history patterns is a hallmark of organismal variation. Related species, populations, and individuals within populations show genetically based variation in life span and other aspects of age-related performance. Population differences are especially informative because these differences can be large relative to within-population variation and because they occur in organisms with otherwise similar genomes.

Age-specific variation in immune response in Drosophila melanogaster has a genetic basis.

Immunosenescence, the age-related decline in immune system function, is a general hallmark of aging. While much is known about the cellular and physiological changes that accompany immunosenescence, we know little about the genetic influences on this phenomenon. In this study we combined age-specific measurements of bacterial clearance ability following infection with whole-genome measurements of the transcriptional response to infection and wounding to identify genes that contribute to the natural variation in immunosenescence, using Drosophila melanogaster as a model system.

A conserved role for syndecan family members in the regulation of whole-body energy metabolism.

Syndecans are a family of type-I transmembrane proteins that are involved in cell-matrix adhesion, migration, neuronal development, and inflammation. Previous quantitative genetic studies pinpointed Drosophila Syndecan (dSdc) as a positional candidate gene affecting variation in fat storage between two Drosophila melanogaster strains. Here, we first used quantitative complementation tests with dSdc mutants to confirm that natural variation in this gene affects variability in Drosophila fat storage.

Age- and diet-specific effects of variation at S6 kinase on life history, metabolic, and immune response traits in Drosophila melanogaster.

Life history theory hypothesizes that genetically based variation in life history traits results from alleles that alter age-specific patterns of energy allocation among the competing demands of reproduction, storage, and maintenance. Despite the important role that alleles with age-specific effects must play in life history evolution, few naturally occurring alleles with age-specific effects on life history traits have been identified. A recent mapping study identified S6 kinase (S6k) as a candidate gene affecting lipid storage in Drosophila.

Systems genetics analysis of body weight and energy metabolism traits in Drosophila melanogaster.

Background: Obesity and phenotypic traits associated with this condition exhibit significant heritability in natural populations of most organisms. While a number of genes and genetic pathways have been implicated to play a role in obesity associated traits, the genetic architecture that underlies the natural variation in these traits is largely unknown. Here, we used 40 wild-derived inbred lines of Drosophila melanogaster to quantify genetic variation in body weight, the content of three major metabolites (glycogen, triacylglycerol, and glycerol) associated with obesity, and metabolic rate in young flies.

Adaptive maternal adjustments of offspring size in response to conspecific density in two populations of the least killifish, Heterandria formosa.

Given a trade-off between offspring size and number and an advantage to large size in competition, theory predicts that the offspring size that maximizes maternal fitness will vary with the level of competition that offspring experience. Where the strength of competition varies, selection should favor females that can adjust their offspring size to match the offspring's expected competitive environment. We looked for such phenotypically plastic maternal effects in the least killifish, Heterandria formosa, a livebearing, matrotrophic species.

Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression.

Chronic inflammation is frequently associated with malignant growth and is thought to promote and enhance tumor progression, although the mechanisms which regulate this relationship remain elusive. We reported previously that interleukin (IL)-1beta promoted tumor progression by enhancing the accumulation of myeloid-derived suppressor cells (MDSC), and hypothesized that inflammation leads to cancer through the production of MDSC which inhibit tumor immunity. If inflammation-induced MDSC promote tumor progression by blocking antitumor immunity, then a reduction in inflammation should reduce MDSC levels and delay tumor progression, whereas an increase in inflammation should increase MDSC levels and hasten tumor progression.

Speed-mapping quantitative trait loci using microarrays.

We developed a rapid, economical method for high-resolution quantitative trait locus (QTL) mapping using microarrays for selective genotyping of pooled DNA samples. We generated 21,207 F2 flies from two inbred Drosophila melanogaster strains with known QTLs affecting lifespan, and hybridized DNA pools of young and old flies to microarrays. We used changes of gene frequency of 2,326 single-feature polymorphisms (SFPs) to map previously identified and additional QTLs affecting lifespan.