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Davis, A.

Publications and source records attributed to Davis, A..

40 records · Page 3Linked to original sources

Accounting for location uncertainty in azimuthal telemetry data improves ecological inference

Characterizing animal space use is critical to understand ecological relationships. Despite many decades of using radio-telemetry to track animals and make spatial inference, there are few statistical options to handle these unique data and no synthetic framework for modeling animal location uncertainty and accounting for it in ecological models. We describe a novel azimuthal telemetry model (ATM) to account for azimuthal uncertainty with covariates and propagate location uncertainty into ecological models. We evaluate the ATM with commonly used estimators in several study design scenarios using simulation. We also provide illustra-tive empirical examples, demonstrating the impact of ignoring location uncertainty within home range and resource selection analyses. We found the ATM to have good performance and the only model that has appropriate measures of coverage. Ignoring animal location un-certainty when estimating resource selection or home ranges can have pernicious effects on ecological inference. We demonstrate that home range estimates can be overly confident and conservative when ignoring location uncertainty and resource selection coefficients can lead to incorrect inference and over confidence in the magnitude of selection. Our findings and model development have important implications for interpreting historical analyses using this type of data and the future design of radio-telemetry studies.

ecology↗

Detection of Pro-apoptotic BaxΔ2 Proteins in the Human Cerebellum

Bax{Delta}2 is a pro-apoptotic protein originally discovered in colon cancer patients with high microsatellite instability. Unlike most pro-apoptotic Bax family members, Bax{Delta}2 mediates cell death through a non-mitochondrial caspase 8-dependent pathway. In the scope of analyzing the distribution of Bax{Delta}2 expression in human tissues, we examined a panel of human brain samples. Here, we report 4 cerebellar cases in which the subjects had no neurological disorder or disease documented. We found Bax{Delta}2 positive cells scattered in all areas of the cerebellum, but most strikingly concentrated in Purkinje cell bodies and dendrites. Two out the four subjects tested had strong Bax{Delta}2- positive staining in nearly all Purkinje cells; one was mainly negative; and one had various levels of positive staining within the same sample. Further genetic analysis of the Purkinje cell layer, collected by microdissection from two subjects, showed that the samples contained G7 and G9 Bax microsatellite mutations. Both subjects were young and had no diseases reported at the time of death. As the distribution of Bax{Delta}2 is consistent with that known for Baxa, but in a less ubiquitous manner, these results may imply a potential function of Bax{Delta}2 in Purkinje cells.

cell biology↗

An epigenetic mechanism for cavefish eye degeneration

Coding and non-coding mutations in DNA contribute significantly to phenotypic variability during evolution. However, less is known about the role of epigenetics in this process. Although previous studies have identified eye development genes associated with the loss of eyes phenotype in the Pachon blind cave morph of the Mexican tetra Astyanax mexicanus1-6, no inactivating mutations have been found in any of these genes2,3,7-10. Here we show that excess DNA methylation-based epigenetic silencing promotes eye degeneration in blind cave Astyanax mexicanus. By performing parallel analyses in Astyanax mexicanus cave and surface morphs and in the zebrafish Danio rerio, we have discovered that DNA methylation mediates eye-specific gene repression and globally regulates early eye development. The most significantly hypermethylated and down-regulated genes in the cave morph are also linked to human eye disorders, suggesting the function of these genes is conserved across the vertebrates. Our results show that changes in DNA methylation-based gene repression can serve as an important molecular mechanism generating phenotypic diversity during development and evolution.

evolutionary biology↗

A Genome-wide Association and Admixture Mapping Study of Bronchodilator Drug Response in African Americans with Asthma

BackgroundShort-acting B2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the U.S 1, 2. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma3\n\nObjectiveTo identify genetic variants that may contribute to differences in BDR in African Americans with asthma.\n\nMethodsWe performed a genome-wide association study of BDR in 949 African American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase 3 genotypes. We used linear regression models adjusting for age, sex, body mass index and genetic ancestry to test for an association between BDR and genotype at single nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1,830 Latinos (Total=2,779). Lastly, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. Two additional populations of 416 Latinos and 1,325 African Americans were used to replicate significant associations.\n\nResultsWe identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p=7.69 x 10-9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958, and rs7081864, p[≤]5 x 10-8).\n\nConclusionsOur findings indicate that both population specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.\n\nKey messagesO_LIA GWAS for BDR in African American children with asthma identified an intergenic population specific variant at 9q21 to be associated with increased bronchodilator drug response (BDR).\nC_LIO_LIA meta-analysis of GWAS across African Americans and Latinos identified shared genetic variants at 10q21 in the intron of PRKG1 to be associated with differences in BDR.\nC_LIO_LIFurther genetic studies need to be performed in diverse populations to identify the full set of genetic variants that contribute to BDR.\nC_LI

genomics↗