Culturally responsive strategies and practical considerations for live tissue studies in Māori participant cohorts

IntroductionIndigenous communities globally are inequitably affected by non-communicable diseases such as cancer and coronary artery disease. Increased focus on personalized medicine approaches for the treatment of these diseases offers opportunities to improve the health of Indigenous people. Conversely, poorly implemented approaches pose increased risk of further exacerbating current inequities in health outcomes for Indigenous peoples. The advancement of modern biology techniques, such as three-dimensional (3D) in vitro models and next generation sequencing (NGS) technologies, have enhanced our understanding of disease mechanisms and individualized treatment responses. However, current representation of Indigenous peoples in these datasets is lacking. It is crucial that there is appropriate and ethical representation of Indigenous peoples in generated datasets to ensure these technologies can be used to maximize the benefit of personalized medicine for Indigenous peoples.MethodsThis project discusses the use of 3D tumor organoids and single cell/nucleus RNA sequencing to study cancer treatment responses and explore immune cell roles in coronary artery disease. Using key pillars from currently available Indigenous bioethics frameworks, strategies were developed for the use of Māori participant samples for live tissue and sequencing studies. These were based on extensive collaborations with local Māori community, scientific leaders, clinical experts, and international collaborators from the Broad Institute of MIT and Harvard. Issues surrounding the use of live tissue, genomic data, sending samples overseas and Indigenous data sovereignty were discussed.ResultsThis paper illustrates a real-world example of how collaboration with community and the incorporation of Indigenous worldviews can be applied to molecular biology studies in a practical and culturally responsive manner, ensuring fair and equitable representation of Indigenous peoples in modern scientific data

A Conserved Function of C. elegans CASY-1 Calsyntenin in Associative Learning

BACKGROUND: Whole-genome association studies in humans have enabled the unbiased discovery of new genes associated with human memory performance. However, such studies do not allow for a functional or causal testing of newly identified candidate genes. Since polymorphisms in Calsyntenin 2 (CLSTN2) showed a significant association with episodic memory performance in humans, we tested the C. elegans CLSTN2 ortholog CASY-1 for possible functions in the associative behavior of C. elegans. METHODOLOGY/PRINCIPAL FINDINGS: Using three different associative learning paradigms and functional rescue experiments, we show that CASY-1 plays an important role during associative learning in C. elegans. Furthermore, neuronal expression of human CLSTN2 in C. elegans rescues the learning defects of casy-1 mutants. Finally, genetic interaction studies and neuron-specific expression experiments suggest that CASY-1 may regulate AMPA-like GLR-1 glutamate receptor signaling. CONCLUSION/SIGNIFICANCE: Our experiments demonstrate a remarkable conservation of the molecular function of Calsyntenins between nematodes and humans and point at a role of C. elegans casy-1 in regulating a glutamate receptor signaling pathway

Watersheds and coral reefs: conservation science, policy,\ud and implementation\ud

Coral reefs worldwide are being degraded by human-induced disturbances, resulting in ecological, economic, and cultural losses. Runoff and sedimentation are among the greatest threats to the coastal reefs surrounding high islands and adjacent to continental landmasses. Existing\ud scientific data identify the key stressors, synergisms, and outcomes at the coral reef ecosystem, community, and population levels. These data demonstrate that marine protected areas alone may be insufficient for coral reef protection; integrated watershed management practices are also needed. Gaps in the effectiveness of environmental policy, legislation, and regulatory enforcement have resulted in the continued degradation of US and Australian reefs. Several Pacific islands, with intact resource stewardship and traditional leadership systems, have been able to apply research findings to coral reef management policies relatively quickly. Three case histories in Micronesia provide insight into how social sciences and\ud biophysical data can be combined to manage human behaviors responsible for coral reef destruction

Heterogeneous Nuclear Ribonucleoprotein (hnRNP) E1 Binds to hnRNP A2 and Inhibits Translation of A2 Response Element mRNAs

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2 is a trans-acting RNA-binding protein that mediates trafficking of RNAs containing the cis-acting A2 response element (A2RE). Previous work has shown that A2RE RNAs are transported to myelin in oligodendrocytes and to dendrites in neurons. hnRNP E1 is an RNA-binding protein that regulates translation of specific mRNAs. Here, we show by yeast two-hybrid analysis, in vivo and in vitro coimmunoprecipitation, in vitro cross-linking, and fluorescence correlation spectroscopy that hnRNP E1 binds to hnRNP A2 and is recruited to A2RE RNA in an hnRNP A2-dependent manner. hnRNP E1 is colocalized with hnRNP A2 and A2RE mRNA in granules in dendrites of oligodendrocytes. Overexpression of hnRNP E1 or microinjection of exogenous hnRNP E1 in neural cells inhibits translation of A2RE mRNA, but not of non-A2RE RNA. Excess hnRNP E1 added to an in vitro translation system reduces translation efficiency of A2RE mRNA, but not of nonA2RE RNA, in an hnRNP A2-dependent manner. These results are consistent with a model where hnRNP E1 recruited to A2RE RNA granules by binding to hnRNP A2 inhibits translation of A2RE RNA during granule transport