Hā Kūpuna National Resource Center for Native Hawaiian Elders: Decolonizing Research through Qualitative Methods and Community Partnership

Housed under the Thompson School of Social Work & Public Health at the University of Hawai‘i at Mānoa, Hā Kūpuna National Resource Center for Native Hawaiian Elders, strives to decolonize Western research as we increase opportunities of Native Hawaiian elders to pass their knowledge and stories to younger generations. One of Hā Kūpuna’s current projects is a five-year qualitative study examining healthcare experiences among Native Hawaiian elders in rural communities to gain advice for medical and social service providers to improve Native Hawaiian health. The project was co-designed by ALU LIKE, Inc.’s Kumu Kahi program (Elderly Services Department), which advised us to conduct a series of three interviews with each elder to build rapport before jumping into questions about healthcare. The first interview focuses on establishing rapport and learning about the kupuna’s family and everyday life. The second interview asks about values they learned from their own kupuna, what they want to pass to their mo`opuna, and other strengths and resiliencies. The third interview hones in on healthcare experiences they had over their lifetime and what advice they would like to share with providers. Results from the first 26 kūpuna have revealed that many kūpuna grew up with limited access to allopathic healthcare (healthcare providers treating diseases and symptoms with drugs and surgery) and that families treated many illnesses and injuries with traditional Hawaiian cultural healing practices, including lāʻau lapaʻau (plant-based medicine), lomilomi (massage), and ho`oponopono (conflict resolution). Even with the increased access and utilization of allopathic medicine, many kūpuna preferred cultural practices or a combination of both. Kūpuna advised that allopathic healthcare providers should take the time to gain knowledge of Native Hawaiian history and culture, allow for use of both Hawaiian and allopathic modes of healing, and interact with patients on both a personal as well as a professional level. They also noted that increasing access to specialty care on Neighbor Islands could improve Native Hawaiian health and life expectancy. Results and experiences from the ALU LIKE interview project helped to inform the creation of a 48-page qualitative interviewing protocol aimed to help researchers avoid extractive practices by increasing their knowledge of Hawaiian history, engaging communities in research, and creating safe and trusting research environments. Although experiences of colonization and discrimination are unique to each Indigenous and minority group, this protocol can apply to other populations as they are at a similar risk for extractive research experiences as well. As elements of the protocols were developed, they were discussed in-depth with researchers, non-profit stakeholders, community-based organization leaders (including ALU LIKE, Inc.), and past research participants. The qualitative protocol includes sections summarizing the history of colonization and instances of poorly-executed research in Hawaiʻi that caused harm. Also included are examples of Native Hawaiian researchers who are changing the face of research, a guide for researcher self-reflection and cultural humility, roles for community members in research, data ownership and management, the need to give more than take from participants, and a step-by-step guide on how to successfully join with community partners to conduct one-on-one interviews. Included are tips on developing research questions, and gathering and reporting data in ways accessible to the community. This qualitative protocol can be used as a guide to decolonizing research. Hā Kūpuna is supported by the US Administration on Community Living (#90OIRC0001) and the Barbara Cox Anthony Endowment

Different Requirement for Wnt/β-Catenin Signaling in Limb Regeneration of Larval and Adult Xenopus

BACKGROUND:In limb regeneration of amphibians, the early steps leading to blastema formation are critical for the success of regeneration, and the initiation of regeneration in an adult limb requires the presence of nerves. Xenopus laevis tadpoles can completely regenerate an amputated limb at the early limb bud stage, and the metamorphosed young adult also regenerates a limb by a nerve-dependent process that results in a spike-like structure. Blockage of Wnt/β-catenin signaling inhibits the initiation of tadpole limb regeneration, but it remains unclear whether limb regeneration in young adults also requires Wnt/β-catenin signaling. METHODOLOGY/PRINCIPAL FINDINGS:We expressed heat-shock-inducible (hs) Dkk1, a Wnt antagonist, in transgenic Xenopus to block Wnt/β-catenin signaling during forelimb regeneration in young adults. hsDkk1 did not inhibit limb regeneration in any of the young adult frogs, though it suppressed Wnt-dependent expression of genes (fgf-8 and cyclin D1). When nerve supply to the limbs was partially removed, however, hsDkk1 expression blocked limb regeneration in young adult frogs. Conversely, activation of Wnt/β-catenin signaling by a GSK-3 inhibitor rescued failure of limb-spike regeneration in young adult frogs after total removal of nerve supply. CONCLUSIONS/SIGNIFICANCE:In contrast to its essential role in tadpole limb regeneration, our results suggest that Wnt/β-catenin signaling is not absolutely essential for limb regeneration in young adults. The different requirement for Wnt/β-catenin signaling in tadpoles and young adults appears to be due to the projection of nerve axons into the limb field. Our observations suggest that nerve-derived signals and Wnt/β-catenin signaling have redundant roles in the initiation of limb regeneration. Our results demonstrate for the first time the different mechanisms of limb regeneration initiation in limb buds (tadpoles) and developed limbs (young adults) with reference to nerve-derived signals and Wnt/β-catenin signaling

Transforming Growth Factor: β Signaling Is Essential for Limb Regeneration in Axolotls

Axolotls (urodele amphibians) have the unique ability, among vertebrates, to perfectly regenerate many parts of their body including limbs, tail, jaw and spinal cord following injury or amputation. The axolotl limb is the most widely used structure as an experimental model to study tissue regeneration. The process is well characterized, requiring multiple cellular and molecular mechanisms. The preparation phase represents the first part of the regeneration process which includes wound healing, cellular migration, dedifferentiation and proliferation. The redevelopment phase represents the second part when dedifferentiated cells stop proliferating and redifferentiate to give rise to all missing structures. In the axolotl, when a limb is amputated, the missing or wounded part is regenerated perfectly without scar formation between the stump and the regenerated structure. Multiple authors have recently highlighted the similarities between the early phases of mammalian wound healing and urodele limb regeneration. In mammals, one very important family of growth factors implicated in the control of almost all aspects of wound healing is the transforming growth factor-beta family (TGF-β). In the present study, the full length sequence of the axolotl TGF-β1 cDNA was isolated. The spatio-temporal expression pattern of TGF-β1 in regenerating limbs shows that this gene is up-regulated during the preparation phase of regeneration. Our results also demonstrate the presence of multiple components of the TGF-β signaling machinery in axolotl cells. By using a specific pharmacological inhibitor of TGF-β type I receptor, SB-431542, we show that TGF-β signaling is required for axolotl limb regeneration. Treatment of regenerating limbs with SB-431542 reveals that cellular proliferation during limb regeneration as well as the expression of genes directly dependent on TGF-β signaling are down-regulated. These data directly implicate TGF-β signaling in the initiation and control of the regeneration process in axolotls

Prenatal Excess Glucocorticoid Exposure and Adult Affective Disorders:A Role for Serotonergic and Catecholamine Pathways

Fetal glucocorticoid exposure is a key mechanism proposed to underlie prenatal ‘programming’ of adult affective behaviours such as depression and anxiety. Indeed, the glucocorticoid metabolising enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which is highly expressed in the placenta and the developing fetus, acts as a protective barrier from the high maternal glucocorticoids which may alter developmental trajectories. The programmed changes resulting from maternal stress or bypass or from the inhibition of 11β-HSD2 are frequently associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis. Hence, circulating glucocorticoid levels are increased either basally or in response to stress accompanied by CNS region-specific modulations in the expression of both corticosteroid receptors (mineralocorticoid and glucocorticoid receptors). Furthermore, early-life glucocorticoid exposure also affects serotonergic and catecholamine pathways within the brain, with changes in both associated neurotransmitters and receptors. Indeed, global removal of 11β-HSD2, an enzyme that inactivates glucocorticoids, increases anxiety‐ and depressive-like behaviour in mice; however, in this case the phenotype is not accompanied by overt perturbation in the HPA axis but, intriguingly, alterations in serotonergic and catecholamine pathways are maintained in this programming model. This review addresses one of the potential adverse effects of glucocorticoid overexposure in utero, i.e. increased incidence of affective behaviours, and the mechanisms underlying these behaviours including alteration of the HPA axis and serotonergic and catecholamine pathways