Participatory approach to community-based curriculum development for the Living With Elephants outreach program in Botswana

There are increasing conflicts arising between humans and elephants throughout Africa and Asia. The Republic of Botswana, which has one of the world’s largest elephant populations, is no exception. One strategy for improving relations between humans and elephants may be participatory and community-based environmental education initiatives. Thus the goal of my project was to work with the non-governmental organization “Living With Elephants Foundation” (LWE) and local Batswanan communities to apply participatory research methods to the collaborative development of an elephant educational outreach program in Botswana. This study describes the process and the results of efforts to collaboratively develop, test and modify educational programming that aimed to contribute to a sustainable relationship between people and elephants. The study had three phases. Phase I involved reviewing academic and nongovernmental organization literature and determining needs of the elephants and people of Botswana through conducting key informant interviews and focus group discussions. Phase II began with an analysis of the initial emergent themes in the data collected in the previous phase in order to develop the goal and objectives and the first draft of the LWE Education Outreach Program. Phase II also involved an evaluation of this version of the program, and was based on student, teacher and community feedback, and the collection of drawings from Botswana students participating in the LWE outreach program. This phase created a space for further revisions, development of follow-up activities, and identification of further needs. Phase III occurred in Canada where I reviewed all the data collected, conducted further analysis as needed and wrote the thesis. This thesis was shared with LWE and a summary will be provided to all interested stakeholders

Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain.

Paralleling the activation of dorsal horn microglia after peripheral nerve injury is a significant expansion and proliferation of macrophages around injured sensory neurons in dorsal root ganglia (DRG). Here we demonstrate a critical contribution of DRG macrophages, but not those at the nerve injury site, to both the initiation and maintenance of the mechanical hypersensitivity that characterizes the neuropathic pain phenotype. In contrast to the reported sexual dimorphism in the microglial contribution to neuropathic pain, depletion of DRG macrophages reduces nerve injury-induced mechanical hypersensitivity and expansion of DRG macrophages in both male and female mice. However, fewer macrophages are induced in the female mice and deletion of colony-stimulating factor 1 from sensory neurons, which prevents nerve injury-induced microglial activation and proliferation, only reduces macrophage expansion in male mice. Finally, we demonstrate molecular cross-talk between axotomized sensory neurons and macrophages, revealing potential peripheral DRG targets for neuropathic pain management

Ablation of spinal cord estrogen receptor α-expressing interneurons reduces chemically induced modalities of pain and itch

Estrogens are presumed to underlie, at least in part, the greater pain sensitivity and chronic pain prevalence that women experience compared to men. Although previous studies revealed populations of estrogen receptor‐expressing neurons in primary afferents and in superficial dorsal horn neurons, there is little to no information as to the contribution of these neurons to the generation of acute and chronic pain. Here we molecularly characterized neurons in the mouse superficial spinal cord dorsal horn that express estrogen receptor α (ERα) and explored the behavioral consequences of their ablation. We found that spinal ERα‐positive neurons are largely excitatory interneurons and many coexpress substance P, a marker for a discrete subset of nociceptive, excitatory interneurons. After viral, caspase‐mediated ablation of spinal ERα‐expressing cells, we observed a significant decrease in the first phase of the formalin test, but in male mice only. ERα‐expressing neuron‐ablation also reduced pruritogen‐induced scratching in both male and female mice. There were no ablation‐related changes in mechanical or heat withdrawal thresholds or in capsaicin‐induced nocifensive behavior. In chronic pain models, we found no change in Complete Freund's adjuvant‐induced thermal or mechanical hypersensitivity, or in partial sciatic nerve injury‐induced mechanical allodynia. We conclude that ERα labels a subpopulation of excitatory interneurons that are specifically involved in chemically evoked persistent pain and pruritogen‐induced itch

Adverse Moisture Events Predict Seasonal Abundance of Lyme Disease Vector Ticks (\u3cem\u3eIxodes scapularis\u3c/em\u3e)

Background Lyme borreliosis (LB) is the most commonly reported vector-borne disease in north temperate regions worldwide, affecting an estimated 300,000 people annually in the United States alone. The incidence of LB is correlated with human exposure to its vector, the blacklegged tick (Ixodes scapularis). To date, attempts to model tick encounter risk based on environmental parameters have been equivocal. Previous studies have not considered (1) the differences between relative humidity (RH) in leaf litter and at weather stations, (2) the RH threshold that affects nymphal blacklegged tick survival, and (3) the time required below the threshold to induce mortality. We clarify the association between environmental moisture and tick survival by presenting a significant relationship between the total number of tick adverse moisture events (TAMEs - calculated as microclimatic periods below a RH threshold) and tick abundance each year. Methods We used a 14-year continuous statewide tick surveillance database and corresponding weather data from Rhode Island (RI), USA, to assess the effects of TAMEs on nymphal populations of I. scapularis. These TAMEs were defined as extended periods of time (\u3e8 h below 82% RH in leaf litter). We fit a sigmoid curve comparing weather station data to those collected by loggers placed in tick habitats to estimate RH experienced by nymphal ticks, and compiled the number of historical TAMEs during the 14-year record. Results The total number of TAMEs in June of each year was negatively related to total seasonal nymphal tick densities, suggesting that sub-threshold humidity episodes \u3e8 h in duration naturally lowered nymphal blacklegged tick abundance. Furthermore, TAMEs were positively related to the ratio of tick abundance early in the season when compared to late season, suggesting that lower than average tick abundance for a given year resulted from tick mortality and not from other factors. Conclusions Our results clarify the mechanism by which environmental moisture affects blacklegged tick populations, and offers the possibility to more accurately predict tick abundance and human LB incidence. We describe a method to forecast LB risk in endemic regions and identify the predictive role of microclimatic moisture conditions on tick encounter risk

Effects of Veliparib on Microglial Activation and Functional Outcomes after Traumatic Brain Injury in the Rat and Pig.

The inflammation response induced by brain trauma can impair recovery. This response requires several hours to develop fully and thus provides a clinically relevant therapeutic window of opportunity. Poly(ADP-ribose) polymerase inhibitors suppress inflammatory responses, including brain microglial activation. We evaluated delayed treatment with veliparib, a poly(ADP-ribose) polymerase inhibitor, currently in clinical trials as a cancer therapeutic, in rats and pigs subjected to controlled cortical impact (CCI). In rats, CCI induced a robust inflammatory response at the lesion margins, scattered cell death in the dentate gyrus, and a delayed, progressive loss of corpus callosum axons. Pre-determined measures of cognitive and motor function showed evidence of attentional deficits that resolved after three weeks and motor deficits that recovered only partially over eight weeks. Veliparib was administered beginning 2 or 24 h after CCI and continued for up to 12 days. Veliparib suppressed CCI-induced microglial activation at doses of 3 mg/kg or higher and reduced reactive astrocytosis and cell death in the dentate gyrus, but had no significant effect on delayed axonal loss or functional recovery. In pigs, CCI similarly induced a perilesional microglial activation that was attenuated by veliparib. CCI in the pig did not, however, induce detectable persisting cognitive or motor impairment. Our results showed veliparib suppression of CCI-induced microglial activation with a delay-to-treatment interval of at least 24 h in both rats and pigs, but with no associated functional improvement. The lack of improvement in long-term recovery underscores the complexities in translating anti-inflammatory effects to clinically relevant outcomes

De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy

X-linked cone dysfunction disorders such as Blue Cone Monochromacy and X-linked Cone Dystrophy are characterized by complete loss (of) or reduced L- and M- cone function due to defects in the OPN1LW/OPN1MW gene cluster. Here we investigated 24 affected males from 16 families with either a structurally intact gene cluster or at least one intact single (hybrid) gene but harbouring rare combinations of common SNPs in exon 3 in single or multiple OPN1LW and OPN1MW gene copies. We assessed twelve different OPN1LW/MW exon 3 haplotypes by semi-quantitative minigene splicing assay. Nine haplotypes resulted in aberrant splicing of ≥20% of transcripts including the known pathogenic haplotypes (i.e. ‘LIAVA’, ‘LVAVA’) with absent or minute amounts of correctly spliced transcripts, respectively. De novo formation of the ‘LIAVA’ haplotype derived from an ancestral less deleterious ‘LIAVS’ haplotype was observed in one family with strikingly different phenotypes among affected family members. We could establish intrachromosomal gene conversion in the male germline as underlying mechanism. Gene conversion in the OPN1LW/OPN1MW genes has been postulated, however, we are first to demonstrate a de novo gene conversion within the lineage of a pedigree

Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma

Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide; however, the molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and of overlapping expression and splicing quantitative trait loci (e/QTLs and sQTLs) in 49 GTEx tissues and retina prioritizesd causal genes for 60% of loci. These genes awere enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues revealesd that the colocalizing genes and genome-wide POAG and IOP associations awere enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominatesd IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis