RESUMO
L1CAM is a transmembrane protein expressed on neurons that was presumed to be found on neuron-derived extracellular vesicles (NDEVs) in human biofluids. We developed a panel of single-molecule array assays to evaluate the use of L1CAM for NDEV isolation. We demonstrate that L1CAM is not associated with extracellular vesicles in human plasma or cerebrospinal fluid and therefore recommend against its use as a marker in NDEV isolation protocols.
Assuntos
Vesículas Extracelulares/metabolismo , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Biomarcadores/metabolismo , Centrifugação , Cromatografia em Gel , Meios de Cultivo Condicionados , Humanos , Molécula L1 de Adesão de Célula Nervosa/sangue , Molécula L1 de Adesão de Célula Nervosa/líquido cefalorraquidiano , Neurônios/metabolismoRESUMO
Precision medicine, also known as "personalised medicine", seeks to identify strategies in the prevention and treatment of disease informed by a patient's genomic information. This allows a targeted approach to disease identification with the intention of reducing the burden of illness. Currently, both the emerging field of precision medicine and the established field of clinical genetics are highly reliant on genomic databases which are fraught with inbuilt biases, particularly from sample populations. The inequities of most concern here are those affecting Aboriginal and Torres Strait Islander (or Zenadth Kes) peoples of Australia (hereafter, respectfully, Indigenous Australians). It is with this perspective that the Summer internship forINdigenous peoples inGenomics Australia endeavours to support the development of culturally appropriate genomic research with Indigenous Australians. We argue here that Indigenous researchers are best placed to create the informed, culturally safe environment necessary for Indigenous Australians to participate in genomic research.
Assuntos
Serviços de Saúde do Indígena , Medicina de Precisão , Humanos , Austrália , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres , Genômica , Equidade em Saúde , Pessoal de Saúde/educação , Medicina de Precisão/métodosRESUMO
Aboriginal Australians represent one of the longest continuous cultural complexes known. Archaeological evidence indicates that Australia and New Guinea were initially settled approximately 50 thousand years ago (ka); however, little is known about the processes underlying the enormous linguistic and phenotypic diversity within Australia. Here we report 111 mitochondrial genomes (mitogenomes) from historical Aboriginal Australian hair samples, whose origins enable us to reconstruct Australian phylogeographic history before European settlement. Marked geographic patterns and deep splits across the major mitochondrial haplogroups imply that the settlement of Australia comprised a single, rapid migration along the east and west coasts that reached southern Australia by 49-45 ka. After continent-wide colonization, strong regional patterns developed and these have survived despite substantial climatic and cultural change during the late Pleistocene and Holocene epochs. Remarkably, we find evidence for the continuous presence of populations in discrete geographic areas dating back to around 50 ka, in agreement with the notable Aboriginal Australian cultural attachment to their country.
Assuntos
Genoma Mitocondrial/genética , Migração Humana/história , Havaiano Nativo ou Outro Ilhéu do Pacífico/genética , Filogeografia , Austrália , Evolução Cultural , DNA Mitocondrial/genética , Haplótipos/genética , História Antiga , Humanos , FilogeniaRESUMO
Environmental epigenetics is increasingly employed to understand the health outcomes of communities who have experienced historical trauma and structural violence. Epigenetics provides a way to think about traumatic events and sustained deprivation as biological "exposures" that contribute to ill-health across generations. In Australia, some Indigenous researchers and clinicians are embracing epigenetic science as a framework for theorising the slow violence of colonialism as it plays out in intergenerational legacies of trauma and illness. However, there is dispute, contention, and caution as well as enthusiasm among these research communities.In this article, we trace strategies of "refusal" (Simpson, 2014) in response to epigenetics in Indigenous contexts. Drawing on ethnographic fieldwork conducted in Australia with researchers and clinicians in Indigenous health, we explore how some construct epigenetics as useless knowledge and a distraction from implementing anti-colonial change, rather than a tool with which to enact change. Secondly, we explore how epigenetics narrows definitions of colonial harm through the optic of molecular trauma, reproducing conditions in which Indigenous people are made intelligible through a lens of "damaged" bodies. Faced with these two concerns, many turn away from epigenetics altogether, refusing its novelty and supposed benefit for Indigenous health equity and resisting the pull of postgenomics.
Assuntos
Colonialismo , Epigenômica , Povos Indígenas , Política , Humanos , Antropologia Cultural , AustráliaRESUMO
BACKGROUND: Aboriginal and Torres Strait Islander people do not enjoy equal access to specialist health services that adequately meet their needs. Clinical genetics services are at the vanguard of realising the health benefits of genomic medicine. As the field continues to expand in clinical utility and implementation, it is critical that Aboriginal and Torres Strait Islander people are able to participate and benefit equally to avoid further widening of the existing health gap. This is the first study to explore barriers to accessing clinical genetics services among Aboriginal and Torres Strait Islander people, which has been acknowledged as a key strategic priority in Australian genomic health policy. METHODS: A participatory design process engaged a majority-Aboriginal Project Reference Group and Aboriginal End-User Group. 63 semi-structured interviews were conducted with Aboriginal and/or Torres Strait Islander people who had accessed the government-funded clinical genetics service in Western Australia, Queensland or the Northern Territory between 2014 and 2018. The sample included patients, parents and carers. Participants were asked to recount their 'patient journey', from referral through to post-appointment and reflect on their perceptions of genetics and its implications for the health of themselves and their families. Analysis tracked chronological service engagement, followed by an inductive thematic approach. RESULTS: Barriers to access and engagement were present at each stage of the patient journey. These included challenges in obtaining a referral, long waiting periods, limited genetic literacy, absence of Aboriginal support services, communication challenges and lack of adequate psychosocial support and follow-up after attendance. Participants' overall experiences of attending a genetic health service were varied, with positive perceptions tied closely to a diagnosis being achieved. The experience of (and expectation for) recognition of cultural identity and provision of culturally safe care was low among participants. Unaddressed concerns continued to cause significant distress in some people years after their appointment took place. CONCLUSIONS: There is significant scope for improving the care provided to Aboriginal and Torres Strait Islander people at clinical genetics services. Immediate attention to minimising logistical barriers, developing relationships with Aboriginal Community Controlled Health Services and providing practical and specific cultural safety training for practitioners is required at the service-level. Our findings strongly support the development of guidelines or policies recognising the collective cultural needs of Aboriginal and Torres Strait Islander people in relation to genomic health care.
Assuntos
Assistência à Saúde Culturalmente Competente , Acessibilidade aos Serviços de Saúde , Serviços de Saúde do Indígena , Disparidades em Assistência à Saúde , Havaiano Nativo ou Outro Ilhéu do Pacífico/psicologia , Competência Cultural , Feminino , Testes Genéticos , Humanos , Entrevistas como Assunto , Masculino , Northern Territory , Pesquisa Qualitativa , Queensland , Austrália OcidentalRESUMO
Several programmable transcription factors exist based on the versatile Cas9 protein, yet their relative potency and effectiveness across various cell types and species remain unexplored. Here, we compare Cas9 activator systems and examine their ability to induce robust gene expression in several human, mouse, and fly cell lines. We also explore the potential for improved activation through the combination of the most potent activator systems, and we assess the role of cooperativity in maximizing gene expression.
Assuntos
Proteínas Associadas a CRISPR/metabolismo , Drosophila melanogaster/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Animais , Células Cultivadas , Drosophila melanogaster/genética , Genes vpr , Engenharia Genética , Humanos , Camundongos , Fatores de Transcrição/genéticaRESUMO
We demonstrate that by altering the length of Cas9-associated guide RNA (gRNA) we were able to control Cas9 nuclease activity and simultaneously perform genome editing and transcriptional regulation with a single Cas9 protein. We exploited these principles to engineer mammalian synthetic circuits with combined transcriptional regulation and kill functions governed by a single multifunctional Cas9 protein.
Assuntos
Sistemas CRISPR-Cas/genética , RNA Guia de Cinetoplastídeos/análise , Sítios de Ligação , Proteínas Associadas a CRISPR/genética , Citometria de Fluxo , Corantes Fluorescentes/análise , Deleção de Genes , Genes Reporter , Engenharia Genética/métodos , Vetores Genéticos , Genoma , Células HEK293 , Humanos , Microscopia de Fluorescência , Mutagênese , Mutação , Edição de RNA , Transcrição GênicaRESUMO
Advances in our understanding of genetic and rare diseases are changing the face of healthcare. Crucially, the global community must implement these advances equitably to reduce health disparities, including between Indigenous and non-Indigenous peoples. We take an Australian perspective to illustrate some key areas that are fundamental to the equitable translation of new knowledge for the improved diagnosis of genetic and rare diseases for Indigenous people. Specifically, we focus on inequalities in access to clinical genetics services and the lack of genetic and phenomic reference data to inform diagnoses. We provide examples of ways in which these inequities are being addressed through Australian partnerships to support a harmonious and inclusive approach to ensure that benefits from traditional wisdom, community knowledge and shared experiences are interwoven to support and inform implementation of new knowledge from genomics and precision public health. This will serve to deliver benefits to all of our diverse citizens, including Indigenous populations.
Assuntos
Variação Genética , Serviços de Saúde do Indígena , Disparidades em Assistência à Saúde , Havaiano Nativo ou Outro Ilhéu do Pacífico/genética , Doenças Raras/genética , Austrália/epidemiologia , Aconselhamento Genético , Predisposição Genética para Doença , Testes Genéticos , Acessibilidade aos Serviços de Saúde , Humanos , Fenótipo , Prognóstico , Doenças Raras/diagnóstico , Doenças Raras/etnologia , Doenças Raras/terapia , Fatores de RiscoRESUMO
Indigenous populations are thought to have particularly low levels of access to genetic health services, and cultural issues may be a contributing factor. This article presents the findings of the first study of genetic health service provision to Indigenous Australians. This qualitative study aimed to identify elements of culturally-competent genetic health service provision in Indigenous Australian contexts. Twelve semi-structured interviews were conducted with genetic counselors and clinical geneticists from around Australia who had delivered services to Indigenous Australians. Participants were asked to describe their experiences and identify any collective cultural needs of Indigenous clients, as well as comment on specific training and resources they had received or used. Interviews were audio-recorded and transcribed with thematic analysis conducted on the data. The findings show that participants were reluctant to generalize the needs of Indigenous peoples. Some participants asserted that Indigenous peoples have needs that differ from the general population, while others felt that there were no collective cultural needs, instead advocating an individualized approach. Being flexible and practical, taking time to build rapport, recognizing different family structures and decision-making processes, as well as socio-economic disadvantage were all identified as important factors in participants' interactions with Indigenous clients. Indigenous support workers and hospital liaison officers were seen as valuable resources for effective service provision. The implications of this study for training and practice are discussed.
Assuntos
Atitude do Pessoal de Saúde , Competência Cultural/psicologia , Aconselhamento Genético/psicologia , Havaiano Nativo ou Outro Ilhéu do Pacífico/psicologia , Adulto , Austrália , Comportamento Cooperativo , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Comunicação Interdisciplinar , Entrevista Psicológica , Masculino , Relações Profissional-Paciente , Pesquisa QualitativaRESUMO
Several studies have reported increased microbial diversity, or distinct microbial community compositions, in the microbiomes of Indigenous peoples around the world. However, there is a widespread failure to include Indigenous cultures and perspectives in microbiome research programmes, and ethical issues pertaining to microbiome research involving Indigenous participants have not received enough attention. We discuss the benefits and risks arising from microbiome research involving Indigenous peoples and analyse microbiome ownership as an ethical concept in this context. We argue that microbiome ownership represents an opportunity for Indigenous peoples to steward and protect their resident microbial communities at every stage of research.
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Povos Indígenas , Propriedade , HumanosRESUMO
The ethics of the scientific study of Ancestors has long been debated by archaeologists, bioanthropologists, and, more recently, ancient DNA (aDNA) researchers. This article responds to the article "Ethics of DNA research on human remains: five globally applicable guidelines" published in 2021 in Nature by a large group of aDNA researchers and collaborators. We argue that these guidelines do not sufficiently consider the interests of community stakeholders, including descendant communities and communities with potential, but yet unestablished, ties to Ancestors. We focus on three main areas of concern with the guidelines. First is the false separation of "scientific" and "community" concerns and the consistent privileging of researcher perspectives over those of community members. Second, the commitment of the guidelines' authors to open data ignores the principles and practice of Indigenous Data Sovereignty. Further, the authors argue that involving community members in decisions about publication and data sharing is unethical. We argue that excluding community perspectives on "ethical" grounds is convenient for researchers, but it is not, in fact, ethical. Third, we stress the risks of not consulting communities that have established or potential ties to Ancestors, using two recent examples from the literature. Ancient DNA researchers cannot focus on the lowest common denominator of research practice, the bare minimum that is legally necessary. Instead, they should be leading multidisciplinary efforts to create processes to ensure communities from all regions of the globe are identified and engaged in research that affects them. This will often present challenges, but we see these challenges as part of the research, rather than a distraction from the scientific endeavor. If a research team does not have the capacity to meaningfully engage communities, questions must be asked about the value and benefit of their research.
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DNA Antigo , Ética em Pesquisa , Genética Humana , Humanos , Família , Grupos Populacionais , Pesquisadores , Genética Humana/ética , Guias como Assunto , Participação dos Interessados , Relações Comunidade-InstituiçãoRESUMO
Globally, there is a recognised need that all populations should be able to access the benefits of genomics and precision medicine. However, achieving this remains constrained by a paucity of data that quantifies access to clinical genomics, particularly amongst Indigenous populations. Using administrative data from clinical genetic health services across three Australian jurisdictions (states/territories), we investigate disparities in the scheduling and attendance of appointments among Aboriginal and/or Torres Strait Islander people, compared to non-Indigenous people. For 14,870 appointments scheduled between 2014-2018, adjusted Multivariate Poisson Regression models revealed that Aboriginal and/or Torres Strait Islander people were scheduled fewer appointments (IRR 0.73 [0.68-0.80], <0.001) and attended at lower rates (IRR 0.85 [0.78-0.93], <0.001). Within this population, adults, females, remote residents, and those presenting in relation to cancer or prenatal indications experienced the greatest disparity in access. These results provide important baseline data related to disparities in access to clinical genomics in Australia.
Assuntos
Povos Indígenas , Havaiano Nativo ou Outro Ilhéu do Pacífico , Adulto , Austrália/epidemiologia , Feminino , Serviços de Saúde , Humanos , Havaiano Nativo ou Outro Ilhéu do Pacífico/genética , Gravidez , Grupos RaciaisRESUMO
PURPOSE: Culturally inappropriate health services contribute to persistent health inequalities. This article reviews approaches to indigenous cultural training for health workers and assesses how effectively they have been translated into training programmes within Australia. DATA SOURCES: CINAHL PLUS, MEDLINE, Wiley InterScience, ATSIHealth and ProQuest. STUDY SELECTION: The review focuses on the conceptual and empirical literature on indigenous cultural training for health workers within selected settler-colonial countries, together with published evaluations of such training programmes in Australia. Data extraction Information on conceptual models underpinning training was extracted descriptively. Details of authors, year, area of investigation, participant group, evaluation method and relevant findings were extracted from published evaluations. RESULTS OF DATA SYNTHESIS: Six models relevant to cultural training were located and organized into a conceptual schema ('cultural competence, transcultural care, cultural safety, cultural awareness, cultural security and cultural respect'). Indigenous cultural training in Australia is most commonly based on a 'cultural awareness' model. Nine published evaluations of Australian indigenous cultural training programmes for health workers were located. Of the three studies that assessed change at multiple points in time, two found positive changes. However, the only study to include a control group found no effect. CONCLUSION: This review shows that the evidence for the effectiveness of indigenous cultural training programmes in Australia is poor. Critiques of cultural training from indigenous and non-indigenous scholars suggest that a 'cultural safety' model may offer the most potential to improve the effectiveness of health services for indigenous Australians.
Assuntos
Competência Cultural/educação , Disparidades em Assistência à Saúde/etnologia , Austrália , Comparação Transcultural , Educação , Humanos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Grupos Populacionais , PreconceitoRESUMO
Objective This study examined the practices and attitudes of Australian biobanks regarding access to samples and data, as well as local and global networking with other biobanks. Methods This was a mixed-methods study, including an online survey of Australian biobank administrators and qualitative interviews with survey participants. The survey examined the criteria applied when considering requests to share or network. The interviews explored attitudes and practices regarding sharing and networking. Results Most (90.9%; 30/33) biobanks offered access to their samples and data to others, principally for research (90.6%; 29/32). The most common criteria used to evaluate access requests included ethical oversight (84.8%; 28/33), scientific merit (84.8%; 28/33) and intended use (81.8%; 27/33). Just over two-thirds (69.7%; 23/33) of biobanks participated in Australian networks, and 39.1% (9/23) participated in global networks. Networking took the form of both sharing standardised operating procedures and policies (60.9%) and sharing samples and data (43.5%). Thirteen of the 16 interviewees participated in networks. Motivations for sharing included scientific necessity, sharing expertise and standardising operations and governance. Significant barriers to networking remain, including insufficient resources, inconsistent regulations and procedures, and cultural and political issues to do with the conduct of research. Conclusions Many Australian biobanks are already active participants in various types of global biobanking. If biobanks are to expand and make the most of their involvement in global networks, then important barriers need to be overcome. What is known about the topic? Biobanks that store human tissue and associated data are increasingly forming local, national and global networks. These networks create opportunities for enhancing the utility and sustainability of biobanks, but also raise considerable technical, legal and ethical challenges. What does this paper add? This paper reports findings from a mixed-methods study of Australian biobanks and reveals contemporary practices and perspectives concerning sample and data sharing, as well as local and global networking. It found most Australian biobanks currently take part in these activities. What are the implications for practitioners? Many Australian biobanks are networking in various ways across regional and national borders. A better understanding of current practices and views on significant and emerging issues is relevant to the diverse range of biobank stakeholders involved in any agenda to expand biobank networking, including patients, consumers, clinicians, scientists, policy makers and regulators.
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Bancos de Espécimes Biológicos , Disseminação de Informação , Atitude , Austrália , Humanos , PublicaçõesRESUMO
The provision of Indigenous cultural training for non-Indigenous health workers has been widely promoted as a method of improving health service provision to 'close the gap' in Indigenous health. However, in the absence of strong evidence, the power of Indigenous cultural training to meaningfully contribute to the health of Aboriginal and Torres Strait Islander peoples remains questionable. This research explored how six hospital-based nurses consider the role of Indigenous cultural training and the impact it has had on their practice through individual semi-structured interviews. Thematic analysis revealed the significance of individual professionals' attitudes in determining the impact of Indigenous cultural training, as well as the need for institutional support to assist in translating Indigenous cultural training into practice. Utilising post-colonial theory, two key findings emerge. First, the way in which Indigenous cultural training conceptualises 'identity' and 'culture' is critical to its ultimate outcomes. Second, deficits in institutional support limit the efficacy of Indigenous cultural training by placing the onus for institutional change on the shoulders of individual health workers.
Assuntos
Competência Cultural , Capacitação em Serviço , Havaiano Nativo ou Outro Ilhéu do Pacífico , Enfermagem , Atitude do Pessoal de Saúde , Austrália , Humanos , Enfermeiras e Enfermeiros/psicologiaRESUMO
BACKGROUND: Aboriginal and Torres Strait Islander people experience a greater burden of disease and die younger than non-Indigenous Australians, with Aboriginal people living in remote areas of the Northern Territory of Australia having the lowest life expectancy estimates. Despite a high burden of chronic disease among Aboriginal and Torres Strait Islander people, access to specialist health services remains low and models of care that increase engagement, may improve health outcomes. METHODS: We describe client and staff perspectives of a model of clinical genetics services provided by the MJD Foundation (MJDF) in geographically and culturally complex contexts within the Northern Territory of Australia. We seek to understand the MJDF model's success in supporting Aboriginal families with the familial, neurodegenerative condition Machado-Joseph disease and how it could be applied in the provision of other specialist services. Thematic analysis was undertaken on semi-structured interviews with primary health care staff (n = 2), Non-Aboriginal MJDF Staff (n = 7) and Aboriginal MJDF Clients / Community workers (n = 13). RESULTS: Four key themes regarding the MJDF model of service delivery were identified with the service being; 1) client led 2) accepting of various understandings of genetic disease causation 3) focused on relationships, continuity and trust between the service provider and the clients, and 4) committed to incorporating an inclusive whole-of-family practice. The MJDF model takes a community-based, person-and family-centred approach to successfully deliver effective specialist genetic health services in remote community settings. We propose that these approaches have broad application in the future design and delivery of specialist health services particularly in culturally complex settings.
Assuntos
Doença Crônica/epidemiologia , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Serviços de Saúde do Indígena , Havaiano Nativo ou Outro Ilhéu do Pacífico/genética , Adolescente , Competência Cultural , Feminino , Humanos , Masculino , Northern Territory/epidemiologia , Atenção Primária à Saúde/métodos , Relações Profissional-PacienteRESUMO
The sequencing of the human genome at the turn of the 21st century was hailed as revealing the overwhelming genetic similarity of human groups. Scholars of genomics have critiqued the subsequent persistence of race-based genetic science, but were reassured that the wide availability of gene sequencing would end the use of race as a proxy for genetic difference. Once an individual's whole gene sequence could be read, they hoped, their ethnoracial classification would become redundant. At the same time, genome science was recognising that the differences between human genomes went beyond the genome sequence to the structure of the genome itself. 'Structural variation' between genomes, including insertions, deletions, translocations, inversions, and copy number variations, mean that the 'universal' reference genome used for genome sequencing is not so universal. As conventional, 'short-read' sequencing wrongly assumes that all genomes have the same structure, significant genetic variation can be missed. This paper examines the twin phenomena that have been posed as a solution to the biases of short-read sequencing: 'long-read' sequencing and 'ethnicity-specific reference genomes'. Long-read sequencing is a method of generating a genome sequence that can be assembled de novo rather than relying on the reference genome. In recent years, a number of countries including China, Korea, and Denmark have used long-read sequencing and de novo assembly to develop 'national' reference genomes. Our analysis of one ethnicity-specific reference genome project, the Korean Reference Genome (KOREF), finds that it unduly emphasises the importance of population structural variation, framed in nationalist terms, and discounts the importance of individual structural variation. We argue that the intellectual labour required to make a Korean reference genome a coherent concept works to extend the horizon of race, prolonging the temporality of the 'meantime' in which race remains a seemingly valid concept in genomic science.
Assuntos
Genoma Humano/genética , Grupos Raciais/genética , Análise de Sequência de DNA/métodos , Antropologia Física , Bases de Dados Genéticas , Variação Genética/genética , Genômica , Humanos , RacismoRESUMO
Aboriginal and Torres Strait Islander Australians experience widespread socioeconomic disadvantage and health inequality. In an attempt to make Indigenous health research more culturally-appropriate, Aboriginal and Torres Strait Islander Australians have called for more attention to the concept of emotional and social wellbeing (ESWB). Although it has been widely recognised that ESWB is of crucial importance to the health of Aboriginal and Torres Strait Islander peoples, there is little consensus on how to measure in Indigenous populations, hampering efforts to better understand and improve the psychosocial determinants of health. This paper explores the policy and political context to this situation, and suggests ways to move forward. The second part of the paper explores how scales can be evaluated in a health research setting, including assessments of endorsement, discrimination, internal and external reliability.We then evaluate the use of a measure of stressful life events, the Negative Life Events Scale (NLES), in two samples of Aboriginal people living in remote communities in the Northern Territory of Australia. We argue that the Negative Life Events Scale is a promising assessment of psychosocial wellbeing in Aboriginal and Torres Strait Islander populations. Evaluation of the scale and its performance in other samples of Aboriginal and Torres Strait Islander populations is imperative if we hope to develop better, rather than more, scales for measuring ESWB among Indigenous Australians. Only then will it be possible to establish standardized methods of measuring ESWB and develop a body of comparable literature that can guide both a better understanding of ESWB, and evaluation of interventions designed to improve the psychosocial health of Indigenous populations and decrease health inequalities.