Space–time home-range estimates and resource selection for the Critically Endangered Philippine Eagle on Mindanao

Quantifying home-range size and habitat resource selection are important elements in wildlife ecology and are useful for informing conservation action. Many home-range estimators and resource selection functions are currently in use. However, both methods are fraught with analytical issues inherent within autocorrelated movement data from irregular sampling and interpretation of resource selection model parameters to inform conservation management. Here, we apply satellite remote sensing technologies to provide updated estimates of home-range size and first estimates of fine-scale resource selection for six adult Philippine Eagles Pithecophaga jefferyi using a space–time autocorrelated kernel density estimate (AKDE) home-range estimator and non-parametric resource selection functions. All six adult Eagles showed distinct site fidelity, with continuous range residency between 2 and 18 km, 1 month after tagging. The space–time AKDE home-range estimators had a median 95% home-range size = 68 km² (95% confidence interval (95% CI) 62–74 km², range: 39–161 km²), with the median 50% core range size = 13 km² (95% CI 11–14 km², range 9–33 km²). From the resource selection functions, all adult Philippine Eagles used habitat high in photosynthetic leaf and canopy structure but avoided areas of old-growth biomass and denser areas of vegetation. This is possibly due to foraging forays into secondary forest and fragmented agricultural areas away from nesting sites. For the first time, we determine two important fine-scale spatial processes for this Critically Endangered raptor that can help in directing conservation management. Rather than employing traditional home-range estimators and resource selection functions, we recommend that analysts consider space–time approaches and non-parametric resource selection functions to animal movement data to explore fully space–time and resource selection.     

Replicating rather than nonreplicating adenovirus-human immunodeficiency virus recombinant vaccines are better at eliciting potent cellular immunity and priming high-titer antibodies

A major challenge in combating the human immunodeficiency virus (HIV) epidemic is the development of vaccines capable of inducing potent, persistent cellular immunity and broadly reactive neutralizing antibody responses to HIV type 1 (HIV-1). We report here the results of a preclinical trial using the chimpanzee model to investigate a combination vaccine strategy involving sequential priming immunizations with different serotypes of adenovirus (Ad)/HIV-1(MN)env/rev recombinants and boosting with an HIV envelope subunit protein, oligomeric HIV(SF162) gp140deltaV2. The immunogenicities of replicating and nonreplicating Ad/HIV-1(MN)env/rev recombinants were compared. Replicating Ad/HIV recombinants were better at eliciting HIV-specific cellular immune responses and better at priming humoral immunity against HIV than nonreplicating Ad-HIV recombinants carrying the same gene insert. Enhanced cellular immunity was manifested by a greater frequency of HIV envelope-specific gamma interferon-secreting peripheral blood lymphocytes and better priming of T-cell proliferative responses. Enhanced humoral immunity was seen in higher anti-envelope binding and neutralizing antibody titers and better induction of antibody-dependent cellular cytotoxicity. More animals primed with replicating Ad recombinants mounted neutralizing antibodies against heterologous R5 viruses after one or two booster immunizations with the mismatched oligomeric HIV-1(SF162) gp140deltaV2 protein. These results support continued development of the replicating Ad-HIV recombinant vaccine approach and suggest that the use of replicating vectors for other vaccines may prove fruitful.     

The limitation of species range: A consequence of searching along resource gradients

Ecological modelers have long puzzled over the spatial distribution of species. The random walk or diffusive approach to dispersal has yielded important results for biology and mathematics, yet it has been inadequate in explaining all phenomenological features. Ranges can terminate non-smoothly absent a complementary shift in the characteristics of the environment. Also unexplained is the absence of a species from nearby areas of adequate, or even abundant, resources. In this paper, I show how local searching behavior–keyed to a density-dependent fitness–can limit the speed and extent of a species’ spread. In contrast to standard diffusive processes, pseudo-rational movement facilitates the clustering of populations. It also can be used to estimate the speed of an expanding population range, explain expansion stall, and provides a mechanism by which a population can colonize seemingly removed regions — biogeographic islands in a continental framework. Finally, I discuss the effect of resource degradation and different resource impact/utilization curves on the model.     

Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

The Kaiser Permanente Research Program on Genes, Environment, and Health (RPGEH) Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort includes DNA specimens extracted from saliva samples of 110,266 individuals. Because of its relationship to aging, telomere length measurement was considered an important biomarker to develop on these subjects. To assay relative telomere length (TL) on this large cohort over a short time period, we created a novel high throughput robotic system for TL analysis and informatics. Samples were run in triplicate, along with control samples, in a randomized design. As part of quality control, we determined the within-sample variability and employed thresholds for the elimination of outlying measurements. Of 106,902 samples assayed, 105,539 (98.7%) passed all quality control (QC) measures. As expected, TL in general showed a decline with age and a sex difference. While telomeres showed a negative correlation with age up to 75 years, in those older than 75 years, age positively correlated with longer telomeres, indicative of an association of longer telomeres with more years of survival in those older than 75. Furthermore, while females in general had longer telomeres than males, this difference was significant only for those older than age 50. An additional novel finding was that the variance of TL between individuals increased with age. This study establishes reliable assay and analysis methodologies for measurement of TL in large, population-based human studies. The GERA cohort represents the largest currently available such resource, linked to comprehensive electronic health and genotype data for analysis.     

Next generation genome-wide association tool: design and coverage of a high-throughput European-optimized SNP array

The success of genome-wide association studies has paralleled the development of efficient genotyping technologies. We describe the development of a next-generation microarray based on the new highly-efficient Affymetrix Axiom genotyping technology that we are using to genotype individuals of European ancestry from the Kaiser Permanente Research Program on Genes, Environment and Health (RPGEH). The array contains 674,517 SNPs, and provides excellent genome-wide as well as gene-based and candidate-SNP coverage. Coverage was calculated using an approach based on imputation and cross validation. Preliminary results for the first 80,301 saliva-derived DNA samples from the RPGEH demonstrate very high quality genotypes, with sample success rates above 94% and over 98% of successful samples having SNP call rates exceeding 98%. At steady state, we have produced 462 million genotypes per week for each Axiom system. The new array provides a valuable addition to the repertoire of tools for large scale genome-wide association studies.     

Dog models of naturally occurring cancer

Studies using dogs provide an ideal solution to the gap in animal models for natural disease and translational medicine. This is evidenced by approximately 400 inherited disorders being characterized in domesticated dogs, most of which are relevant to humans. There are several hundred isolated populations of dogs (breeds) and each has a vastly reduced genetic variation compared with humans; this simplifies disease mapping and pharmacogenomics.?Dogs age five- to eight-fold faster than do humans, share environments with their owners, are usually kept until old age and receive a high level of health care. Farseeing investigators recognized this potential and, over the past decade, have developed the necessary tools and infrastructure to utilize this powerful model of human disease, including the sequencing of the dog genome in 2005. Here, we review the nascent convergence of genetic and translational canine models of spontaneous disease, focusing on cancer.     

Alpha 1 adrenergic receptor control of renal blood vessels during aging

Aging humans and rats have a reduced renal vascular constriction response to stress, change in posture, or exercise. In this study, renal interlobar arteries from 9- (intermediate age) to 15-month-old (aging) male Wistar rats constricted less to alpha-adrenergic agonists than those of 4-month-old (young adult) rats. The reduced contraction to A61603 (alpha 1 A agonist) was similar to that to norepinephrine and phenylephrine. Therefore, it appears that the reduction in constriction is primarily related to alpha 1 A receptor stimulation. GeneChip microarray hybridization analysis of the interlobar arteries with the RAE 230A GeneChip indicated that there were no significant differences in gene expression for alpha 1 A/C, 1B, or 1D receptors between 4-month-old (young adult) and 1-year-old (aging) male Wistar rats. Competitive binding experiments (prazosin) revealed that maximal binding (Bmax, fmol/mg protein) of the alpha 1 receptors of interlobar arteries was reduced 25% by 10 months of age and 50% by 18+ months of age. Alpha 1 receptor-induced arterial constriction and prazosin binding were both down-regulated. The loss of receptor-initiated constriction likely includes down-regulation of maximum agonist binding by alpha 1 adrenergic receptors.     

Gait alterations in rats following attachment of a device and application of altered knee loading

Animal models are widely used to study cartilage degeneration. Experimental interventions to alter contact mechanics in articular joints may also affect the loads borne by the leg during gait and consequently affect the overall loading experienced in the joint. In this study, force plate analyses were utilized to measure parameters of gait in the rear legs of adult rats following application of a varus loading device that altered loading in the knee. Adult rats were assigned to Control, Sham, or Loaded groups (n≥4/each). Varus loading devices were surgically attached to rats in the Sham and Loaded groups. In the Loaded group, this device applied a controlled compressive overload to the medial compartment of the knee during periods of engagement. Peak ground reaction forces during walking were recorded for each rear leg of each group. Analyses of variance were used to compare outcomes across groups (Control, Sham, and Loaded), leg (contralateral, experimental) and device status (disengaged, engaged) to determine the effects of surgically attaching the device and applying a compressive overload to the joint with the device. The mean peak vertical force in the experimental leg was reduced to 30% in the Sham group in comparison to the contralateral leg and the Control group, indicating an effect of attaching the device to the leg (p<0.01). No differences were found in ground reaction forces between the Sham and Loaded groups with application of compressive overloads with the device. The significant reduction in vertical force due to the surgical attachment of the varus loading device must be considered and accounted for in future studies.