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1.
Nature ; 587(7835): 632-637, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32731256

RESUMO

Members of the conserved Argonaute protein family use small RNA guides to locate their mRNA targets and regulate gene expression and suppress mobile genetic elements in eukaryotes1,2. Argonautes are also present in many bacterial and archaeal species3-5. Unlike eukaryotic proteins, several prokaryotic Argonaute proteins use small DNA guides to cleave DNA, a process known as DNA interference6-10. However, the natural functions and targets of DNA interference are poorly understood, and the mechanisms of DNA guide generation and target discrimination remain unknown. Here we analyse the activity of a bacterial Argonaute nuclease from Clostridium butyricum (CbAgo) in vivo. We show that CbAgo targets multicopy genetic elements and suppresses the propagation of plasmids and infection by phages. CbAgo induces DNA interference between homologous sequences and triggers DNA degradation at double-strand breaks in the target DNA. The loading of CbAgo with locus-specific small DNA guides depends on both its intrinsic endonuclease activity and the cellular double-strand break repair machinery. A similar interaction was reported for the acquisition of new spacers during CRISPR adaptation, and prokaryotic genomes that encode Ago nucleases are enriched in CRISPR-Cas systems. These results identify molecular mechanisms that generate guides for DNA interference and suggest that the recognition of foreign nucleic acids by prokaryotic defence systems involves common principles.


Assuntos
Proteínas Argonautas/metabolismo , Clostridium butyricum/enzimologia , DNA/metabolismo , Inativação Gênica , Bacteriófagos/genética , Bacteriófagos/fisiologia , Biocatálise , Sistemas CRISPR-Cas , Clostridium butyricum/genética , Clostridium butyricum/virologia , DNA/genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Exodesoxirribonuclease V/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , Homologia de Sequência do Ácido Nucleico
2.
PLoS Genet ; 17(8): e1009717, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34432790

RESUMO

Accurate repair of DNA double-strand breaks (DSBs) is crucial for cell survival and genome integrity. In Escherichia coli, DSBs are repaired by homologous recombination (HR), using an undamaged sister chromosome as template. The DNA intermediates of this pathway are expected to be branched molecules that may include 4-way structures termed Holliday junctions (HJs), and 3-way structures such as D-loops and repair forks. Using a tool creating a site-specific, repairable DSB on only one of a pair of replicating sister chromosomes, we have determined how these branched DNA intermediates are distributed across a DNA region that is undergoing DSB repair. In cells, where branch migration and cleavage of HJs are limited by inactivation of the RuvABC complex, HJs and repair forks are principally accumulated within a distance of 12 kb from sites of recombination initiation, known as Chi, on each side of the engineered DSB. These branched DNA structures can even be detected in the region of DNA between the Chi sites flanking the DSB, a DNA segment not expected to be engaged in recombination initiation, and potentially degraded by RecBCD nuclease action. This is observed even in the absence of the branch migration and helicase activities of RuvAB, RadA, RecG, RecQ and PriA. The detection of full-length DNA fragments containing HJs in this central region implies that DSB repair can restore the two intact chromosomes, into which HJs can relocate prior to their resolution. The distribution of recombination intermediates across the 12kb region beyond Chi is altered in xonA, recJ and recQ mutants suggesting that, in the RecBCD pathway of DSB repair, exonuclease I stimulates the formation of repair forks and that RecJQ promotes strand-invasion at a distance from the recombination initiation sites.


Assuntos
Reparo do DNA/genética , DNA Cruciforme/genética , Escherichia coli/genética , Proteínas de Bactérias/genética , Cromossomos Bacterianos/metabolismo , Quebras de DNA de Cadeia Dupla , DNA Helicases/genética , Reparo do DNA/fisiologia , Replicação do DNA , DNA Bacteriano/genética , DNA Cruciforme/metabolismo , Proteínas de Escherichia coli/genética , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Recombinação Homóloga
3.
Mol Cell ; 60(3): 344-5, 2015 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-26545073

RESUMO

DNA inversion duplications are genome rearrangements observed in cancer. In this issue, Deng et al. (2015) demonstrate that in S. cerevisiae RPA and Mre11-Sae2 cooperate to prevent the formation of inversion duplications initiated at short DNA secondary structures.


Assuntos
Endodesoxirribonucleases/metabolismo , Endonucleases/metabolismo , Exodesoxirribonucleases/metabolismo , Amplificação de Genes , Sequências Repetidas Invertidas , Proteína de Replicação A/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo
4.
PLoS Genet ; 16(1): e1008473, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31895943

RESUMO

To prevent the transmission of damaged genomic material between generations, cells require a system for accommodating DNA repair within their cell cycles. We have previously shown that Escherichia coli cells subject to a single, repairable site-specific DNA double-strand break (DSB) per DNA replication cycle reach a new average cell length, with a negligible effect on population growth rate. We show here that this new cell size distribution is caused by a DSB repair-dependent delay in completion of cell division. This delay occurs despite unperturbed cell size regulated initiation of both chromosomal DNA replication and cell division. Furthermore, despite DSB repair altering the profile of DNA replication across the genome, the time required to complete chromosomal duplication is invariant. The delay in completion of cell division is accompanied by a DSB repair-dependent delay in individualization of sister nucleoids. We suggest that DSB repair events create inter-sister connections that persist until those chromosomes are separated by a closing septum.


Assuntos
Divisão Celular , Cromossomos Bacterianos/genética , Reparo de DNA por Recombinação , Quebras de DNA de Cadeia Dupla , Escherichia coli
5.
Health Promot Int ; 38(4)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37590384

RESUMO

In 2020, a government-funded healthy school lunch program was introduced in a quarter of New Zealand schools, selected due to high levels of socio-economic barriers. This study assesses the impact of the introduction of the school lunch program from family (whanau), student and school principal perspectives. Across four schools, we conducted five focus groups (two with secondary students and three with family members) and four school principal interviews. Participating schools represented a range of contexts: primary and secondary, schools with cooks in on-site kitchens and schools receiving meals delivered by external caterers. Thematic analysis was used to develop themes describing the health, wellbeing and nutritional impact of the program. Family participants were 82% Indigenous Maori and self-identified as having 'borderline' (73.5%) or no financial security (8.8%). Seven positive impact themes were identified: improved food security, enhanced equity, increased appreciation of healthy foods for students, enhanced mana (wellbeing) for all, reduced financial hardship/stress for families, opportunities for nutritional learning and recognition that appreciation and uptake happen over time. Four negative impact themes were identified: low uptake that created food waste, perception that healthy food is not palatable for students, lack of knowledge of the program and loss of agency for students. This is the largest intervention in nutrition and food security for children implemented in New Zealand since the 1930's. The first 2 years have offered wellbeing and financial benefits for students and families, particularly when school environments promote uptake. More involvement of students and family members in the program planning is essential.


Assuntos
Saúde da Criança , Povo Maori , Refeições , Serviços de Saúde Escolar , Criança , Humanos , Nova Zelândia , Eliminação de Resíduos , Instituições Acadêmicas , Nível de Saúde , Estado Nutricional
6.
Molecules ; 28(21)2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37959841

RESUMO

Haemodorum coccineum, commonly known as scarlet bloodroot, is a plant native to New Guinea and the northern most parts of Australia. The highly coloured H. coccineum is used by communities in Larrakia country for dyeing garments and occasionally to treat snake bites. Previous studies into H. coccineum have focused on its taxonomic classification, with this being the first evaluation of the chemical composition of the plant. Haemodoraceae plants are reported to contain phenylphenalenones (PhPs), which are highly conjugated polycyclic oxygenated aromatic hydrocarbons. We report the characterisation of 20 compounds extracted from the rhizome of H. coccineum: four sugars and 16 compounds belonging to the PhP family. The compounds include five aglycones and seven glycosylated compounds, of which four contain malonate esters in their structures. Characterisation of these compounds was achieved through 1D and 2D NMR, MS analysis and comparison to the known phytochemistry of other species from the Haemodorum genus. Preliminary anti-microbial activity of the crude extract shows significant inhibition of the growth of both gram-positive and gram-negative bacteria, but no activity against Candida albicans.


Assuntos
Rizoma , Sanguinaria , Rizoma/química , Antibacterianos/farmacologia , Antibacterianos/análise , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Extratos Vegetais/química , Testes de Sensibilidade Microbiana
7.
Am J Kidney Dis ; 80(1): 20-29.e1, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35151826

RESUMO

RATIONALE & OBJECTIVE: In Aotearoa/New Zealand, Indigenous Maori experience inequitable delivery of kidney transplantation despite disproportionately higher rates of kidney failure. This study describes Maori patients' and families' values, perspectives, and experiences related to kidney transplantation. STUDY DESIGN: Qualitative interview study. SETTING & PARTICIPANTS: We conducted 40 in-depth interviews of 40 Maori: 8 who had received a transplant, 20 with chronic kidney disease (which included 10 on the deceased donor transplant list, 9 who were interested in transplantation and not currently waitlisted or who were ineligible for waitlisting, and 1 who was not interested in transplantation), 4 live-kidney donors, and 8 family members including 6 who had experiences with donor assessment. ANALYTICAL APPROACH: Data were analyzed inductively to generate themes and a conceptual framework. RESULTS: We identified 5 major themes: actively seeking a kidney transplant; evolving attitudes toward traditional values and practices; being confronted by interpersonal and systemic racism; poor information and communication; and challenged by social determinants of health. LIMITATIONS: Participants were recruited nationally through patient advocacy organizations and 1 regional kidney service. Potential participants unrelated to these groups or region could not be included. CONCLUSIONS: Maori participants were highly motivated to seek kidney transplantation and were inspired by positive experiences through donating and receiving a kidney. However, they faced barriers including social determinants, racism, and lack of information that impacted both direct experiences of transplantation and access to transplantation services.


Assuntos
Transplante de Rim , Racismo , Humanos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Nova Zelândia , Pesquisa Qualitativa
8.
Nephrology (Carlton) ; 27(5): 421-429, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34985814

RESUMO

AIMS: People with chronic kidney disease (CKD) living in rural communities have increased risks of death, morbidity, hospitalization and poorer quality of life compared with people with CKD living in urban areas. This study explores the experiences and perceptions of rural and remote patients and families in relation to accessing health services for kidney disease in Aotearoa New Zealand. METHODS: We conducted an In-depth interview study. We purposively sampled adult patients with CKD and their caregivers who lived further than 100 km (62 miles) or more than 1 h drive from their nearest dialysis or transplant centre. Qualitative data were analyzed inductively to generate themes, subthemes and a conceptual framework. RESULTS: Of 35 participants, including 26 patients and nine caregivers, 51% were female, 71% travelled between 1 and 3 h to their nearest renal unit, and the remainder, between 3 and 6 h. We identified five themes and related subthemes: intense psychological impact of rurality; pressure of extended periods away from home; services not designed for rural and remote living; suffering from financial losses; and poor communication. CONCLUSION: Rural and remote patients with CKD and their caregivers face the added challenges of separation from family, social and community support and financial burden, which can have profound consequences on their psychological and physical well-being and that of their families.


Assuntos
Insuficiência Renal Crônica , Serviços de Saúde Rural , Adulto , Feminino , Serviços de Saúde , Humanos , Nova Zelândia/epidemiologia , Pesquisa Qualitativa , Qualidade de Vida , Diálise Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , População Rural
9.
Molecules ; 27(12)2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35745000

RESUMO

This study aims to investigate the combined anti-inflammatory activity of ginger and turmeric extracts. By comparing the activities of individual and combined extracts in lipopolysaccharide and interferon-γ-induced murine RAW 264.7 cells, we demonstrated that ginger-turmeric combination was optimal at a specific ratio (5:2, w/w) in inhibiting nitric oxide, tumour necrosis factor and interleukin 6 with synergistic interaction (combination index < 1). The synergistic inhibitory effect on TNF was confirmed in human monocyte THP-1 cells. Ginger-turmeric combination (5:2, w/w) also upregulated nuclear factor erythroid 2−related factor 2 activity and heme oxygenase-1 protein expression. Additionally, 6-shogaol, 8-shogaol, 10-shogaol and curcumin were the leading compounds in reducing major proinflammatory mediators and cytokines, and a simplified compound combination of 6-s, 10-s and curcumin showed the greatest potency in reducing LPS-induced NO production. Our study provides scientific evidence in support of the combined use of ginger and turmeric to alleviate inflammatory processes.


Assuntos
Curcumina , Zingiber officinale , Animais , Anti-Inflamatórios/farmacologia , Curcuma/metabolismo , Curcumina/farmacologia , Zingiber officinale/metabolismo , Heme Oxigenase-1 , Humanos , Interferon gama , Lipopolissacarídeos , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/farmacologia
10.
Health Promot J Austr ; 33(3): 631-641, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34674331

RESUMO

ISSUE ADDRESSED: Hawke's Bay has one of the highest rates of childhood obesity in New Zealand. While several initiatives exist aiming to decrease obesity through physical activity, there are few nutritional interventions. This study adopted a systems science and matauranga Maori approach to identify and target underlying drivers of rising childhood obesity and engage the community to improve the food environment. METHODS: Cognitive mapping interviews (CM) with local stakeholders (school principals, Iwi and district health board representatives, education managers and local councillors) were conducted. The aim was to map participants' mental models of the causes of rising childhood obesity and to identify key principles for engaging with the local community in a meaningful, impactful and culturally appropriate way for future action. RESULTS: Eleven interviews were conducted face-to-face and cognitive maps were constructed. Follow-up interviews were carried out online, due to COVID restrictions, to present the maps and for interviewees to make any adjustments. Four composite themes emerged through centrality and cluster analysis of the resulting cognitive maps: the importance of building in matauranga Maori (Maori knowledge and ways of being), the "hauora" of children, working with the community and integrating existing initiatives. Two contextual factors are also considered: the growing need for food security in our communities and the opportunity to start interventions in the school setting. CONCLUSION: Cognitive mapping can produce useful insights in the early stages of community engagement. The six "pou" (pillars) underscore the importance of incorporating indigenous knowledge when embarking on public health interventions, particularly around obesity and in regional communities. SO WHAT?: When designing a public health initiative with a community with a high indigenous population, indigenous knowledge should be promoted to focus on holistic health, working with the community and creating opportunities for cohesion. These founding principles will be used to structure future community actions to improve children's food environments in regional New Zealand.


Assuntos
COVID-19 , Obesidade Infantil , Criança , Cognição , Humanos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Nova Zelândia , Obesidade Infantil/prevenção & controle
11.
Public Health Nutr ; 24(18): 6015-6026, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33966689

RESUMO

OBJECTIVE: To understand motivators, facilitators and challenges to dietary change amongst a diverse sample of New Zealanders with prediabetes participating in a primary care nurse-led individualised dietary intervention. DESIGN: A qualitative study involving semi-structured, face-to-face interviews with a stratified sample of adults with prediabetes and BMI ≥ 25 kg/m2, purposefully selected from a larger 2-year primary care-based prediabetes dietary intervention study. Thematic analysis was undertaken. A socio-ecological model guided interpretation. SETTING: Hawke's Bay, Aotearoa/New Zealand, April 2018-March 2020. PARTICIPANTS: Fifty-eight people aged 28-69 years, with similar numbers of men and women, indigenous Maori and non-Maori, and those who had and had not regressed to normoglycaemia at 6 months. RESULTS: Motivators for wanting to make dietary changes were determination not to progress to diabetes; wanting to be healthy and contribute to others and encouragement by others. Facilitators for adopting and maintaining changes were a strong desire to be healthy; personal determination and feeling supported. Challenges were compromised control over life and environmental factors; feeling unsupported by others; social occasions; financial constraints and living with other health conditions. Developing their own strategies to overcome challenges was empowering, enabling a sense of control. These factors were similar across demographic and glycaemic outcome groups. CONCLUSIONS: Influences on dietary change involved personal, interpersonal, organisational, environmental and policy factors. Although findings appeared similar across groups, dietary interventions need to address the specific ways motivators, facilitators and challenges manifest for individuals and social groups and be tailored accordingly within the context of the wider obesogenic and socio-economic environment.


Assuntos
Diabetes Mellitus , Estado Pré-Diabético , Enfermagem de Atenção Primária , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Pesquisa Qualitativa
12.
PLoS Genet ; 14(3): e1007256, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29522563

RESUMO

It was recently reported that the recBC mutants of Escherichia coli, deficient for DNA double-strand break (DSB) repair, have a decreased copy number of their terminus region. We previously showed that this deficit resulted from DNA loss after post-replicative breakage of one of the two sister-chromosome termini at cell division. A viable cell and a dead cell devoid of terminus region were thus produced and, intriguingly, the reaction was transmitted to the following generations. Using genome marker frequency profiling and observation by microscopy of specific DNA loci within the terminus, we reveal here the origin of this phenomenon. We observed that terminus DNA loss was reduced in a recA mutant by the double-strand DNA degradation activity of RecBCD. The terminus-less cell produced at the first cell division was less prone to divide than the one produced at the next generation. DNA loss was not heritable if the chromosome was linearized in the terminus and occurred at chromosome termini that were unable to segregate after replication. We propose that in a recB mutant replication fork breakage results in the persistence of a linear DNA tail attached to a circular chromosome. Segregation of the linear and circular parts of this "σ-replicating chromosome" causes terminus DNA breakage during cell division. One daughter cell inherits a truncated linear chromosome and is not viable. The other inherits a circular chromosome attached to a linear tail ending in the chromosome terminus. Replication extends this tail, while degradation of its extremity results in terminus DNA loss. Repeated generation and segregation of new σ-replicating chromosomes explains the heritability of post-replicative breakage. Our results allow us to determine that in E. coli at each generation, 18% of cells are subject to replication fork breakage at dispersed, potentially random, chromosomal locations.


Assuntos
Cromossomos Bacterianos , Quebras de DNA de Cadeia Dupla , Replicação do DNA , DNA Bacteriano/genética , DNA Circular/genética , Escherichia coli/genética , Divisão Celular , Reparo do DNA , Escherichia coli/citologia , Proteínas de Escherichia coli/metabolismo , Exodesoxirribonuclease V/metabolismo , Microscopia de Fluorescência , Modelos Biológicos , Mutação
13.
Nucleic Acids Res ; 46(13): 6670-6682, 2018 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-29901759

RESUMO

DNA double-strand break (DSB) repair is critical for cell survival. A diverse range of organisms from bacteria to humans rely on homologous recombination for accurate DSB repair. This requires both coordinate action of the two ends of a DSB and stringent control of the resultant DNA replication to prevent unwarranted DNA amplification and aneuploidy. In Escherichia coli, RecBCD enzyme is responsible for the initial steps of homologous recombination. Previous work has revealed recD mutants to be nuclease defective but recombination proficient. Despite this proficiency, we show here that a recD null mutant is defective for the repair of a two-ended DSB and that this defect is associated with unregulated chromosome amplification and defective chromosome segregation. Our results demonstrate that RecBCD plays an important role in avoiding this amplification by coordinating the two recombining ends in a manner that prevents divergent replication forks progressing away from the DSB site.


Assuntos
Cromossomos Bacterianos , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteínas de Escherichia coli/fisiologia , Exodesoxirribonuclease V/fisiologia , Divisão Celular , Segregação de Cromossomos , Clivagem do DNA , DNA Bacteriano/análise , Desoxirribonucleases/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Exodesoxirribonuclease V/genética , Exonucleases/metabolismo , Mutação , Recombinação Genética
14.
PLoS Genet ; 13(10): e1006895, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28968392

RESUMO

Marker frequency analysis of the Escherichia coli recB mutant chromosome has revealed a deficit of DNA in a specific zone of the terminus, centred on the dif/TerC region. Using fluorescence microscopy of a marked chromosomal site, we show that the dif region is lost after replication completion, at the time of cell division, in one daughter cell only, and that the phenomenon is transmitted to progeny. Analysis by marker frequency and microscopy shows that the position of DNA loss is not defined by the replication fork merging point since it still occurs in the dif/TerC region when the replication fork trap is displaced in strains harbouring ectopic Ter sites. Terminus DNA loss in the recB mutant is also independent of dimer resolution by XerCD at dif and of Topo IV action close to dif. It occurs in the terminus region, at the point of inversion of the GC skew, which is also the point of convergence of specific sequence motifs like KOPS and Chi sites, regardless of whether the convergence of GC skew is at dif (wild-type) or a newly created sequence. In the absence of FtsK-driven DNA translocation, terminus DNA loss is less precisely targeted to the KOPS convergence sequence, but occurs at a similar frequency and follows the same pattern as in FtsK+ cells. Importantly, using ftsIts, ftsAts division mutants and cephalexin treated cells, we show that DNA loss of the dif region in the recB mutant is decreased by the inactivation of cell division. We propose that it results from septum-induced chromosome breakage, and largely contributes to the low viability of the recB mutant.


Assuntos
Cromossomos Bacterianos/genética , Quebras de DNA de Cadeia Dupla , Proteínas de Escherichia coli/genética , Escherichia coli/genética , Exodesoxirribonuclease V/genética , Divisão Celular , Reparo do DNA , Replicação do DNA , DNA Bacteriano/genética , Proteínas de Escherichia coli/metabolismo , Exodesoxirribonuclease V/metabolismo , Análise de Sequência de DNA
15.
Int J Equity Health ; 18(1): 74, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118025

RESUMO

BACKGROUND: The prevalence of smoking during pregnancy among indigenous women approaches 50% and is associated with sudden infant death, pregnancy loss, preterm delivery, low birth weight, and anatomical deformity. This study aims to synthesise qualitative studies by reporting experiences, perceptions, and values of smoking cessation among pregnant indigenous women to inform potential interventions. METHOD: A highly-sensitive search of MEDLINE, Embase, PsychINFO, and CINAHL, in conjunction with analysis of Google Scholar and reference lists of related studies was conducted in March 2018. We utilised two methods (thematic synthesis and an indigenous Maori analytical framework) in parallel to analyse data. Completeness of reporting in studies was evaluated using the Consolidated Criteria for Reporting Qualitative Studies (COREQ) framework. RESULTS: We included seven studies from Australia and New Zealand involving 250 indigenous women. Three themes were identified. Realising well-being and creating agency included giving the best start to baby, pride in being a healthy mum, female role models, and family support. Understanding the drivers for smoking included the impact of stress and chaos that hindered prioritisation of self-care, the social acceptability of smoking, guilt and feeling judged, and inadequate information about the risks of smoking. Indigenous women strongly preferred culturally responsive approaches to smoking cessation, placing value on programs designed specifically for and by indigenous people, that were accessible, and provided an alternative to smoking. CONCLUSION: Future interventions and smoking cessation programmes might be more effective and acceptable to indigenous women and families when they harness self-agency and the desire for a healthy baby, recognise the high value of indigenous peer involvement, and embed a social focus in place of smoking as a way to maintain community support and relationships. Development and evaluation of smoking cessation programs for pregnant indigenous women and families is warranted.


Assuntos
Grupos Populacionais/psicologia , Gestantes/etnologia , Abandono do Hábito de Fumar/etnologia , Austrália , Feminino , Humanos , Nova Zelândia , Grupos Populacionais/estatística & dados numéricos , Gravidez , Gestantes/psicologia , Pesquisa Qualitativa , Abandono do Hábito de Fumar/psicologia , Valores Sociais/etnologia
16.
Int J Equity Health ; 18(1): 204, 2019 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-31888651

RESUMO

BACKGROUND: Kidney transplantation is considered best practice treatment for end stage kidney disease (ESKD), however Indigenous patients are substantially less likely to receive either a deceased or live donor kidney transplant than non-Indigenous patients. We describe Indigenous peoples' experiences and perspectives including traditional values around kidney transplantation to inform international transplant programs. METHODS: We conducted a systematic review of qualitative studies involving Indigenous adults who have experience with or perceptions of kidney transplantation. We searched MEDLINE, Embase, PsychINFO, and CINAHL, in conjunction with analysis of Google Scholar and reference lists of related studies till July 2019. We utilised thematic synthesis to analyse data. Completeness of reporting in studies was evaluated using the Consolidated Criteria for Reporting Qualitative Studies (COREQ) framework. RESULTS: Eight studies involving 225 Indigenous participants were included. Five themes were identified: strong desire for transplantation (seeking normality and freedom from dialysis, wanting to reduce burden of disease within community); lack of partnership in shared decision-making (receiving inadequate information, ineffective communication); barriers to live kidney donation (difficulty asking, apprehension about impact on donor, avoiding additional financial burden and fear of complications); cultural considerations (influence of traditional values and beliefs, reconciling traditional values with pragmatic need); and experiencing lack of cultural competence in clinical care (struggling with prejudice and ignorance, mistrust of clinicians and health system). CONCLUSION: Indigenous participants had a strong desire for a kidney transplant and recognised the need for more readily available kidney transplants for others in their communities with ESKD. However, they faced prejudice and a lack of cultural competence by health workers as well as wider barriers to transplantation in systems that did not support effective and culturally appropriate delivery of information and care. Traditional cultural values also influenced decisions regarding kidney transplantation but such values were moderated when considering transplantation. Transplantation programs need to identify and mitigate barriers, such as the financial burden, promote cultural safety and incorporate traditional values into the promotion of transplantation in order to address inequitable transplantation rates. REGISTRATION: Not applicable.


Assuntos
Atitude Frente a Saúde/etnologia , Povos Indígenas/psicologia , Falência Renal Crônica/etnologia , Transplante de Rim/psicologia , Competência Cultural , Humanos , Falência Renal Crônica/terapia , Preconceito , Pesquisa Qualitativa , Valores Sociais
17.
Int J Equity Health ; 18(1): 174, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727076

RESUMO

BACKGROUND: Eliminating indigenous and ethnic health inequities requires addressing the determinants of health inequities which includes institutionalised racism, and ensuring a health care system that delivers appropriate and equitable care. There is growing recognition of the importance of cultural competency and cultural safety at both individual health practitioner and organisational levels to achieve equitable health care. Some jurisdictions have included cultural competency in health professional licensing legislation, health professional accreditation standards, and pre-service and in-service training programmes. However, there are mixed definitions and understandings of cultural competency and cultural safety, and how best to achieve them. METHODS: A literature review of 59 international articles on the definitions of cultural competency and cultural safety was undertaken. Findings were contextualised to the cultural competency legislation, statements and initiatives present within Aotearoa New Zealand, a national Symposium on Cultural Competence and Maori Health, convened by the Medical Council of New Zealand and Te Ohu Rata o Aotearoa - Maori Medical Practitioners Association (Te ORA) and consultation with Maori medical practitioners via Te ORA. RESULTS: Health practitioners, healthcare organisations and health systems need to be engaged in working towards cultural safety and critical consciousness. To do this, they must be prepared to critique the 'taken for granted' power structures and be prepared to challenge their own culture and cultural systems rather than prioritise becoming 'competent' in the cultures of others. The objective of cultural safety activities also needs to be clearly linked to achieving health equity. Healthcare organisations and authorities need to be held accountable for providing culturally safe care, as defined by patients and their communities, and as measured through progress towards achieving health equity. CONCLUSIONS: A move to cultural safety rather than cultural competency is recommended. We propose a definition for cultural safety that we believe to be more fit for purpose in achieving health equity, and clarify the essential principles and practical steps to operationalise this approach in healthcare organisations and workforce development. The unintended consequences of a narrow or limited understanding of cultural competency are discussed, along with recommendations for how a broader conceptualisation of these terms is important.


Assuntos
Competência Cultural , Assistência à Saúde Culturalmente Competente/métodos , Assistência à Saúde Culturalmente Competente/estatística & dados numéricos , Equidade em Saúde/estatística & dados numéricos , Etnicidade , Feminino , Humanos , Nova Zelândia , Grupos Populacionais
18.
PLoS Genet ; 12(2): e1005799, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26872352

RESUMO

Homologous recombination provides a mechanism of DNA double-strand break repair (DSBR) that requires an intact, homologous template for DNA synthesis. When DNA synthesis associated with DSBR is convergent, the broken DNA strands are replaced and repair is accurate. However, if divergent DNA synthesis is established, over-replication of flanking DNA may occur with deleterious consequences. The RecG protein of Escherichia coli is a helicase and translocase that can re-model 3-way and 4-way DNA structures such as replication forks and Holliday junctions. However, the primary role of RecG in live cells has remained elusive. Here we show that, in the absence of RecG, attempted DSBR is accompanied by divergent DNA replication at the site of an induced chromosomal DNA double-strand break. Furthermore, DNA double-stand ends are generated in a recG mutant at sites known to block replication forks. These double-strand ends, also trigger DSBR and the divergent DNA replication characteristic of this mutant, which can explain over-replication of the terminus region of the chromosome. The loss of DNA associated with unwinding joint molecules previously observed in the absence of RuvAB and RecG, is suppressed by a helicase deficient PriA mutation (priA300), arguing that the action of RecG ensures that PriA is bound correctly on D-loops to direct DNA replication rather than to unwind joint molecules. This has led us to put forward a revised model of homologous recombination in which the re-modelling of branched intermediates by RecG plays a fundamental role in directing DNA synthesis and thus maintaining genomic stability.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , DNA Bacteriano/biossíntese , Proteínas de Escherichia coli/metabolismo , Imunoprecipitação da Cromatina , Cromossomos Bacterianos/metabolismo , Replicação do DNA , Proteínas de Escherichia coli/genética , Modelos Biológicos , Mutação/genética , Recombinação Genética
19.
Mol Cell ; 39(1): 59-70, 2010 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-20603075

RESUMO

Survival and genome stability are critical characteristics of healthy cells. DNA palindromes pose a threat to genome stability and have been shown to participate in a reaction leading to the formation of inverted chromosome duplications centered around themselves. There is considerable interest in the mechanism of this rearrangement given its likely contribution to genome instability in cancer cells. This study shows that formation of large inverted chromosome duplications can be observed in the chromosome of Escherichia coli. They are formed at the site of a 246 bp interrupted DNA palindrome in the absence of the hairpin nuclease SbcCD and the recombination protein RecA. The genetic requirements for this spontaneous rearrangement are consistent with a pathway involving DNA degradation and hairpin formation, as opposed to a cruciform cleavage pathway. Accordingly, the formation of palindrome-dependent hairpin intermediates can be induced by an adjacent DNA double-stand break.


Assuntos
Cromossomos Bacterianos/metabolismo , Desoxirribonucleases/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/enzimologia , Exonucleases/metabolismo , Rearranjo Gênico , Sequências Repetidas Invertidas/genética , Recombinases Rec A/metabolismo , Pareamento de Bases/genética , Quebras de DNA de Cadeia Dupla , Replicação do DNA , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Escherichia coli/genética , Microscopia , Modelos Biológicos , Recombinação Genética/genética
20.
BMC Pediatr ; 18(1): 299, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30208860

RESUMO

BACKGROUND: Although breastfeeding duration in New Zealand's indigenous Maori is shorter than in non-Maori, we know little about barriers or motivators of breastfeeding in this community. The aim of this analysis was to identify predictors for extended duration of breastfeeding amongst participants drawn from predominantly Maori communities in regional Hawke's Bay. METHODS: Mother/baby dyads were recruited from two midwifery practices serving predominantly Maori women in mostly deprived areas, for a randomised controlled trial comparing the risks and benefits of an indigenous sleeping device (wahakura) and a bassinet. Questionnaires were administered at baseline (pregnancy) and at one, three and six months postnatal. Several questions relating to breastfeeding and factors associated with breastfeeding were included. The data from both groups were pooled to examine predictors of breastfeeding duration. RESULTS: Maori comprised 70.5% of the 197 participants recruited. The median time infants were fully breastfed was eight weeks and Maori women were more likely to breastfeed for a shorter duration than New Zealand European women with an odds-ratio (OR) of 0.45 (95% CI 0.24, 0.85). The key predictors for extended duration of breastfeeding were the strong support of the mother's partner (OR = 3.64, 95% CI 1.76, 7.55) or her mother for breastfeeding (OR = 2.47, 95% CI 1.27, 4.82), longer intended duration of maternal breastfeeding (OR = 1.02, 95% CI 1.00, 1.03) and being an older mother (OR = 1.07, 95% CI 1.02, 1.12). The key predictors for shorter duration of breastfeeding were pacifier use (OR = 0.28, 95% CI 0.17, 0.46), daily cigarette smoking (OR = 0.51, 95% CI 0.37, 0.69), alcohol use (OR = 0.54, 95% CI 0.31, 0.93) and living in a more deprived area (OR 0.40, 95% CI 0.22, 0.72). CONCLUSIONS: Breastfeeding duration in this group of mainly Maori women was shorter than the national average. Increasing the duration of breastfeeding by these mothers could be further facilitated by ante and postnatal education involving their own mothers and their partners in the support of breastfeeding and by addressing pacifier use, smoking and alcohol use.


Assuntos
Aleitamento Materno/estatística & dados numéricos , Etnicidade , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Idade Materna , Havaiano Nativo ou Outro Ilhéu do Pacífico , Nova Zelândia/epidemiologia , Chupetas/estatística & dados numéricos , Áreas de Pobreza , Fumar/epidemiologia , Fatores de Tempo
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