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1.
Obes Rev ; 24 Suppl 2: e13631, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37753597

RESUMO

Social media use is integral to many adolescents' lives. It brings benefits but can also have detrimental effects on both physical and mental health. We conducted a systematic review examining associations between social media use, adolescent mental health (including body image, self-esteem, stress, interpersonal relationships and loneliness, anxiety, and depressive symptoms), and dietary outcomes. Quantitative studies published between 2019 and 2023 investigating both mental health and diet were searched in 11 databases. The risk of bias was appraised using ROBINS-E. Data were narratively synthesized by type of association, PROGRESS-Plus health equity characteristics, and related to social media influencers. Twenty-one studies were included, of which only one focused on influencers. Sex/gender was the only equity characteristic assessed (n = 8), with mixed results. The findings suggest significant positive correlations between social media use and both depressive and disordered eating symptoms, body dissatisfaction, and anxiety. Four studies identified body image, self-esteem, or anxiety as moderators acting between social media exposure and dietary outcomes. Policy interventions mitigating the impact of social media on adolescents-particularly body image and disordered eating-are needed, alongside follow-up studies on causal pathways, the role of influencers, equity impacts, dietary intake, and the best measurement tools to use.

2.
Obes Rev ; 24 Suppl 2: e13624, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37753598

RESUMO

The CO-CREATE project aimed to work with young people to create, inform, and disseminate obesity-preventive evidence-based policies using a complex systems perspective. This paper draws lessons from this experience and proposes a protocol for embedding systems thinking within a research project. We first draw on existing systems thinking frameworks to analyze how systems thinking was translated across CO-CREATE, including the flow and relationship between the work packages and in the methods used. We then take the lessons from CO-CREATE and the principles of existing systems thinking frameworks-which focus on various points of intervention planning and delivery but not on research projects as a whole-to formulate a protocol for embedding systems thinking across a research project. Key lessons for future planning and delivery of systems-oriented research projects include incorporating "boundary critique" by capturing key stakeholder (adolescent) values and concerns; working to avoid social exclusion; ensuring methodological pluralism to allow for reflection and responsiveness (with methods ranging from group model building, Photovoice, and small group engagement); getting policy recipients to shape key questions by understanding their views on the critical drivers of obesity early on in the project; and providing opportunity for intraproject reflection along the way.

3.
Obes Rev ; 24 Suppl 2: e13623, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37753599

RESUMO

Despite growing recognition of the importance of applying a systems lens to action on obesity, there has only been limited analysis of the extent to which this lens has actually been applied. The CO-CREATE project used a youth-led participatory action research approach to generate policy ideas towards the reduction of adolescent overweight and obesity across Europe. In order to assess the extent to which these youth-generated policy ideas take a systems approach, we analyzed them using the Intervention Level Framework (ILF). The ILF ascribes actions to one of five system levels, from Structural Elements, the least engaged with system change, up to Paradigm, which is the system's deepest held beliefs and thus the most difficult level at which to intervene. Of the 106 policy ideas generated by young people during the CO-CREATE project, 91 (86%) were categorized at the level of Structural Elements. This emphasis on operational rather than systems level responses echoes findings from a previous study on obesity strategies. Analyzing the distribution of systems level responses using the ILF has the potential to support more effective action on obesity by allowing identification of opportunities to strengthen systems level responses overall.


Assuntos
Obesidade , Políticas , Adolescente , Humanos , Obesidade/prevenção & controle
4.
Obes Rev ; 24 Suppl 2: e13628, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37753604

RESUMO

Both obesity and poor mental wellbeing have a high prevalence in European youth. Adolescents in six countries identified mental wellbeing factors as main drivers of youth obesity through systems mapping. This study sought to (1) explore the dynamics of the interplay between poor mental wellbeing, energy balance-related behaviors, and adolescent overweight and obesity prevalence and (2) test the effect of intervention point scenarios to reduce adolescent obesity. Drawing on the youth-generated systems maps and a literature synthesis, we built a simulation model that represents the links from major feedback pathways for poor mental wellbeing to changes in dietary, physical activity, and sleep behaviors. The model was calibrated using survey data from Norway, expert input, and literature and shows a good fit between simulated behavior and available statistical data. The simulations indicate that adolescent mental wellbeing is harmed by socio-cultural pressures and stressors, which trigger reinforcing feedback mechanisms related to emotional/binge eating, lack of motivation to engage in physical activity, and sleep difficulty. Targeting a combination of intervention points that support a 25% reduction of pressure on body image and psychosocial stress showed potentially favorable effects on mental wellbeing-doubling on average for boys and girls and decreasing obesity prevalence by over 4%.


Assuntos
Obesidade Infantil , Masculino , Feminino , Adolescente , Humanos , Prevalência , Obesidade Infantil/epidemiologia , Motivação , Emoções , Saúde Mental
5.
Obes Rev ; 24 Suppl 2: e13629, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37753607

RESUMO

Energy balance-related behaviors (EBRBs) are considered the immediate causes of adolescents' body weight increases, but adolescents have identified mental health as a contributor. Cross-sectional studies have reported associations between adolescents' mental health and obesity, but causal relationships and the role of EBRBs within this can only be established using longitudinal studies. This systematic review summarizes the findings of longitudinal studies investigating this relationship, in addition to the role of EBRB in the relationship. Multiple electronic databases were searched for longitudinal studies using keywords related to the adolescent population, mental health, EBRB, and body weight. In total, 1216 references were identified and screened based on previously defined eligibility criteria. Sixteen articles met the inclusion criteria. Most studies indicated that mental health-related measures like depression, anxiety, and body dissatisfaction were related to an increase in body weight later. As this review is focused on behavioral mediators, six studies reported associations between mental health-anthropometry dyad and EBRBs such as eating habits, screen time, physical activity, and sleep-as well as stressors like peer victimization. Future studies may focus on streamlining mental health measures and body weight outcomes to assess this relationship. Furthermore, more longitudinal investigations are needed to provide insight into the role of EBRBs in the mental health-body weight relationship during adolescence.


Assuntos
Saúde Mental , Obesidade , Adolescente , Humanos , Estudos Transversais , Antropometria , Peso Corporal
6.
Syst Rev ; 12(1): 165, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710334

RESUMO

BACKGROUND: The field of the commercial determinants of health (CDOH) refers to the commercial products, pathways and practices that may affect health. The field is growing rapidly, as evidenced by the WHO programme on the economic and commercial determinants of health and a rise in researcher and funder interest. Systematic reviews (SRs) and evidence synthesis more generally will be crucial tools in the evolution of CDOH as a field. Such reviews can draw on existing methodological guidance, though there are areas where existing methods are likely to differ, and there is no overarching guidance on the conduct of CDOH-focussed systematic reviews, or guidance on the specific methodological and conceptual challenges. METHODS/RESULTS: CODES provides guidance on the conduct of systematic reviews focussed on CDOH, from shaping the review question with input from stakeholders, to disseminating the review. Existing guidance was used to identify key stages and to provide a structure for the guidance. The writing group included experience in systematic reviews and other forms of evidence synthesis, and in equity and CDOH research (both primary research and systematic reviews). CONCLUSIONS: This guidance highlights the special methodological and other considerations for CDOH reviews, including equity considerations, and pointers to areas for future methodological and guideline development. It should contribute to the reliability and utility of CDOH reviews and help stimulate the production of reviews in this growing field.


Assuntos
Qualidade da Assistência à Saúde , Pesquisadores , Humanos , Reprodutibilidade dos Testes , Revisões Sistemáticas como Assunto
7.
Can J Microbiol ; 69(11): 416-431, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37552890

RESUMO

Deinococcus murrayi is a bacterium isolated from hot springs in Portugal, and named after Dr. Robert G.E. Murray in recognition of his research on the genus Deinococcus. Like other Deinococcus species, D. murrayi is extremely resistant to ionizing radiation. Repair of massive DNA damage and limitation of oxidative protein damage are two important factors contributing to the robustness of Deinococcus bacteria. Here, we identify, among others, the DNA repair and oxidative stress defense proteins in D. murrayi, and highlight special features of D. murrayi. For DNA repair, D. murrayi does not contain a standalone uracil-DNA glycosylase (Ung), but it encodes a protein in which Ung is fused to a DNA photolyase domain (PhrB). UvrB and UvrD contain large insertions corresponding to inteins. One of its endonuclease III enzymes lacks a [4Fe-4S] cluster. Deinococcus murrayi possesses a homolog of the error-prone DNA polymerase IV. Concerning oxidative stress defense, D. murrayi encodes a manganese catalase in addition to a heme catalase. Its organic hydroperoxide resistance protein Ohr is atypical because the redox active cysteines are present in a CXXC motif. These and other characteristics of D. murrayi show further diversity among Deinococcus bacteria with respect to resistance-associated mechanisms.


Assuntos
Deinococcus , Estresse Oxidativo , Reparo do DNA , Deinococcus/genética , Deinococcus/metabolismo , Dano ao DNA , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
8.
Obes Rev ; 24 Suppl 1: e13544, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36623282

RESUMO

The objective of this scoping review is to understand the extent and impact of youth involvement in policy processes within public health, education, and social work. Youth involvement in policy processes may enhance the relevance of policies and strengthen democratic practices. This scoping review aims to explore the nature, extent, and impact of youth involvement in policy processes in public health, education, and social work, with a focus on health, well-being, and obesity prevention. Empirical studies published from 1989 and evaluating involvement of youth aged 10 to 19 years old from all socioeconomic backgrounds and countries. Studies will be searched in seven databases. Data will be extracted and synthesized narratively by rights-based perspectives on youth involvement, practical processes of the involvement, and social experiences using descriptive statistics and visuals.


Assuntos
Política de Saúde , Saúde Pública , Humanos , Adolescente , Criança , Adulto Jovem , Adulto , Saúde Pública/métodos , Escolaridade , Obesidade , Serviço Social , Literatura de Revisão como Assunto
9.
Syst Rev ; 11(1): 232, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36303235

RESUMO

BACKGROUND: This systematic overview was commissioned by England's Department of Health and Social Care (DHSC) to assess the evidence on direct (previously 'novel') oral anticoagulants (OACs), compared with usual care, in adults, to prevent stroke related to atrial fibrillation (AF), and to prevent and treat venous thromboembolism (VTE). Specifically, to assess efficacy and safety, genotyping, self-monitoring, and patient and clinician experiences of OACs. METHODS: We searched MEDLINE, Embase, ASSIA, and CINAHL, in October, 2017, updated in November 2021. We included systematic reviews, published from 2014, in English, assessing OACs, in adults. We rated review quality using AMSTAR2 or the JBI checklist. Two reviewers extracted and synthesised the main findings from the included reviews. RESULTS: We included 49 systematic reviews; one evaluated efficacy, safety, and cost-effectiveness, 17 assessed genotyping, 23 self-monitoring or adherence, and 15 experiences (seven assessed two topics). Generally, the direct OACs, particularly apixaban (5 mg twice daily), were more effective and safer than warfarin in preventing AF-related stroke. For VTE, there was little evidence of differences in efficacy between direct OACs and low-molecular-weight heparin (prevention), warfarin (treatment), and warfarin or aspirin (secondary prevention). The evidence suggested that some direct OACs may reduce the risk of bleeding, compared with warfarin. One review of genotype-guided warfarin dosing assessed AF patients; no significant differences in stroke prevention were reported. Education about OACs, in patients with AF, could improve adherence. Pharmacist management of coagulation may be better than primary care management. Patients were more adherent to direct OACs than warfarin. Drug efficacy was highly valued by patients and most clinicians, followed by safety. No other factors consistently affected patients' choice of anticoagulant and adherence to treatment. Patients were more satisfied with direct OACs than warfarin. CONCLUSIONS: For stroke prevention in AF, direct OACs seem to be more effective and safer than usual care, and apixaban (5 mg twice daily) had the best profile. For VTE, there was no strong evidence that direct OACs were better than usual care. Education and pharmacist management could improve coagulation control. Both clinicians and patients rated efficacy and safety as the most important factors in managing AF and VTE. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017084263-one deviation; efficacy and safety were from one review.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia Venosa , Humanos , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Genótipo , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Varfarina/uso terapêutico , Literatura de Revisão como Assunto
10.
BMC Public Health ; 22(1): 1307, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799156

RESUMO

BACKGROUND: Lyme disease incidence is increasing in Europe, the USA, and Canada. In 2010, a comparison of surveillance systems for Lyme disease (LD) in humans in 28 European countries showed that systems highly varied, making epidemiological comparisons difficult. Details by country were not published. In 2018, one of LD clinical manifestations, neuroborreliosis, was added under European Union (EU) surveillance to standardise definitions. In this study, we identified and compared, 10 years after the European inventory, the characteristics of national surveillance systems and policies for LD in humans, with additional countries. METHODS: Thirty-four European and North American countries were included. Information on national "traditional" systems (which compile data reported by clinicians and laboratories) and "public participatory" websites and mobile applications (which collect information directly from the public) were searched in MEDLINE, a systematic evidence map, and Google. An existing framework on LD surveillance was adapted to capture information on the administration level, indicators, reporting entities, coverage, and obligation to report. RESULTS: A surveillance system was found for 29 (85%) countries. Twenty-four had a traditional system alone, one had a public participatory system alone, and the remaining had both. Among countries with traditional systems, 23 (82%) administered them at the national level. Nineteen (68%) required mandatory reporting. Sixteen (57%) used both clinicians and laboratories as reporting entities. Eighteen (64%) employed case definitions, most of which considered both neuroborreliosis and erythema migrans (n = 14). Others monitored the number of positive laboratory tests and/or patient consultations. Public participatory systems were only implemented in countries employing either also sentinels or voluntary surveys, or no traditional system, suggesting their use as a complementary tool. Only 56% of EU countries had neuroborreliosis as an indicator. CONCLUSION: The situation remains similar to 2010 with persisting heterogeneity between systems, suggesting that countries prioritise different surveillance objectives for LD. Without a common indicator in Europe, it is difficult to get a clear epidemiological picture. We discuss four factors that potentially influence LD surveillance strategies: perceptions of severity, burden on resources, two-way communication, and the medical conflicts about LD. Addressing these with countries might help moving towards the adoption of common practices.


Assuntos
Doença de Lyme , Políticas , Vigilância da População , Europa (Continente)/epidemiologia , Humanos , Doença de Lyme/epidemiologia , América do Norte/epidemiologia
11.
Antioxidants (Basel) ; 11(3)2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35326211

RESUMO

Deinococcus species possess remarkable tolerance to extreme environmental conditions that generate oxidative damage to macromolecules. Among enzymes fulfilling key functions in metabolism regulation and stress responses, thiol reductases (TRs) harbour catalytic cysteines modulating the redox status of Cys and Met in partner proteins. We present here a detailed description of Deinococcus TRs regarding gene occurrence, sequence features, and physiological functions that remain poorly characterised in this genus. Two NADPH-dependent thiol-based systems are present in Deinococcus. One involves thioredoxins, disulfide reductases providing electrons to protein partners involved notably in peroxide scavenging or in preserving protein redox status. The other is based on bacillithiol, a low-molecular-weight redox molecule, and bacilliredoxin, which together protect Cys residues against overoxidation. Deinococcus species possess various types of thiol peroxidases whose electron supply depends either on NADPH via thioredoxins or on NADH via lipoylated proteins. Recent data gained on deletion mutants confirmed the importance of TRs in Deinococcus tolerance to oxidative treatments, but additional investigations are needed to delineate the redox network in which they operate, and their precise physiological roles. The large palette of Deinococcus TR representatives very likely constitutes an asset for the maintenance of redox homeostasis in harsh stress conditions.

12.
Health Educ Res ; 36(5): 581-599, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-34312670

RESUMO

Health-Promoting School (HPS) interventions aim to reduce bullying and violence via curriculum, environmental and family/community-engagement components. Despite evidence of their effectiveness, factors influencing the implementation of such interventions are poorly understood. This systematic review aims to examine such factors by assessing qualitative process evaluations of HPS interventions aiming to reduce bullying, aggression or violence. A comprehensive systematic search of 12 databases was carried out, and 20 reports from 17 studies were included. Thematic synthesis was used to identify factors affecting implementation. Factors that enable implementation were related to programme characteristics and stakeholder buy-in, including support from leadership, teachers, students and parents. Good communication and staff climate were important. Interventions were better implemented when they framed health promotion as a core school business, were supported by a national policy, used local data to show need and effectiveness and provided high-quality, pragmatic and accessible staff training. The results of this review can serve to guide and facilitate the design and implementation of future bullying and violence prevention programmes. Since there is significant overlap in terms of the important pillars and guiding principles for all interventions guided by the HPS framework, the findings may apply to outcomes beyond bullying and violence.


Assuntos
Bullying , Bullying/prevenção & controle , Promoção da Saúde , Humanos , Instituições Acadêmicas , Estudantes , Violência/prevenção & controle
13.
Plant J ; 108(5): 1507-1521, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34612534

RESUMO

STOP1, an Arabidopsis transcription factor favouring root growth tolerance against Al toxicity, acts in the response to iron under low Pi (-Pi). Previous studies have shown that Al and Fe regulate the stability and accumulation of STOP1 in roots, and that the STOP1 protein is sumoylated by an unknown E3 ligase. Here, using a forward genetics suppressor screen, we identified the E3 SUMO (small ubiquitin-like modifier) ligase SIZ1 as a modulator of STOP1 signalling. Mutations in SIZ1 increase the expression of ALMT1 (a direct target of STOP1) and root growth responses to Al and Fe stress in a STOP1-dependent manner. Moreover, loss-of-function mutations in SIZ1 enhance the abundance of STOP1 in the root tip. However, no sumoylated STOP1 protein was detected by Western blot analysis in our sumoylation assay in Escherichia coli, suggesting the presence of a more sophisticated mechanism. We conclude that the sumo ligase SIZ1 negatively regulates STOP1 signalling, at least in part by modulating STOP1 protein in the root tip. Our results will allow a better understanding of this signalling pathway.


Assuntos
Alumínio/toxicidade , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Ferro/toxicidade , Ligases/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Ligases/genética , Mutação , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Estresse Fisiológico , Sumoilação , Fatores de Transcrição/genética
14.
Antioxidants (Basel) ; 10(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34356381

RESUMO

Deinococcus radiodurans is a robust bacterium with extraordinary resistance to ionizing radiation and reactive oxygen species (ROS). D. radiodurans produces an antioxidant thiol compound called bacillithiol (BSH), but BSH-related enzymes have not been investigated. The D. radiodurans mutant lacking bshA (dr_1555), the first gene of the BSH biosynthetic pathway, was devoid of BSH and sensitive to hydrogen peroxide (H2O2) compared to the wild-type D. radiodurans strain. Three bacilliredoxin (Brx) proteins, BrxA, B, and C, have been identified in BSH-producing bacteria, such as Bacillus. D. radiodurans possesses DR_1832, a putative homolog of BrxC. However, because DR_1832 contains a novel signature motif (TCHKT) and a C-terminal region similar to the colicin-like immunity domain, we named it AbxC (atypical BrxC). The deletion of abxC also sensitized cells to H2O2. AbxC exhibited peroxidase activity in vitro, which was linked to nicotinamide adenine dinucleotide phosphate (NADPH) oxidation via the BSH disulfide reductase DR_2623 (DrBdr). AbxC proteins were present mainly as dimers after exposure to H2O2 in vitro, and the oxidized dimers were resolved to monomers by the reaction coupled with BSH as an electron donor, in which DrBdr transported reducing equivalents from NADPH to AbxC through BSH recycling. We identified 25 D. radiodurans proteins that potentially interact with AbxC using AbxC-affinity chromatography. Most of them are associated with cellular metabolisms, such as glycolysis and amino acid biosynthesis, and stress response. Interestingly, AbxC could bind to the proposed peroxide-sensing transcription regulator, DrOxyR. These results suggest that AbxC may be involved in the H2O2 signaling mechanism mediated by DrOxyR.

15.
Cells ; 10(4)2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33923690

RESUMO

Deinococcus bacteria are extremely resistant to radiation and able to repair a shattered genome in an essentially error-free manner after exposure to high doses of radiation or prolonged desiccation. An efficient, SOS-independent response mechanism to induce various DNA repair genes such as recA is essential for radiation resistance. This pathway, called radiation/desiccation response, is controlled by metallopeptidase IrrE and repressor DdrO that are highly conserved in Deinococcus. Among various Deinococcus species, Deinococcus radiodurans has been studied most extensively. Its genome encodes classical DNA repair proteins for error-free repair but no error-prone translesion DNA polymerases, which may suggest that absence of mutagenic lesion bypass is crucial for error-free repair of massive DNA damage. However, many other radiation-resistant Deinococcus species do possess translesion polymerases, and radiation-induced mutagenesis has been demonstrated. At least dozens of Deinococcus species contain a mutagenesis cassette, and some even two cassettes, encoding error-prone translesion polymerase DnaE2 and two other proteins, ImuY and ImuB-C, that are probable accessory factors required for DnaE2 activity. Expression of this mutagenesis cassette is under control of the SOS regulators RecA and LexA. In this paper, we review both the RecA/LexA-controlled mutagenesis and the IrrE/DdrO-controlled radiation/desiccation response in Deinococcus.


Assuntos
Reparo do DNA/genética , Deinococcus/genética , Regulação Bacteriana da Expressão Gênica , Tolerância a Radiação/genética , Resposta SOS em Genética/genética , Mutagênese/genética
16.
Sci Rep ; 11(1): 4528, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33633226

RESUMO

Deinococcus bacteria are extremely resistant to radiation and other DNA damage- and oxidative stress-generating conditions. An efficient SOS-independent response mechanism inducing expression of several DNA repair genes is essential for this resistance, and is controlled by metalloprotease IrrE that cleaves and inactivates transcriptional repressor DdrO. Here, we identify the molecular signaling mechanism that triggers DdrO cleavage. We show that reactive oxygen species (ROS) stimulate the zinc-dependent metalloprotease activity of IrrE in Deinococcus. Sudden exposure of Deinococcus to zinc excess also rapidly induces DdrO cleavage, but is not accompanied by ROS production and DNA damage. Further, oxidative treatment leads to an increase of intracellular free zinc, indicating that IrrE activity is very likely stimulated directly by elevated levels of available zinc ions. We conclude that radiation and oxidative stress induce changes in redox homeostasis that result in IrrE activation by zinc in Deinococcus. We propose that a part of the zinc pool coordinated with cysteine thiolates is released due to their oxidation. Predicted regulation systems involving IrrE- and DdrO-like proteins are present in many bacteria, including pathogens, suggesting that such a redox signaling pathway including zinc as a second messenger is widespread and participates in various stress responses.


Assuntos
Deinococcus/metabolismo , Deinococcus/efeitos da radiação , Oxirredução , Tolerância a Radiação , Transdução de Sinais , Zinco/metabolismo , Dano ao DNA , Replicação do DNA , Deinococcus/genética , Regulação Bacteriana da Expressão Gênica/efeitos da radiação , Metaloproteases/genética , Metaloproteases/metabolismo , Modelos Biológicos , Mutagênese , Estresse Oxidativo , Radiação Ionizante
17.
Trials ; 21(1): 286, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197623

RESUMO

Generalisability is typically only briefly mentioned in discussion sections of evaluation articles, which are unhelpful in judging whether an intervention could be implemented elsewhere, with similar effects. Several tools to assess generalisability exist, but they are difficult to operationalise and are rarely used. We believe a different approach is needed. Instead of focusing on similarities (or more likely, differences) in generic population and setting characteristics, generalisability assessments should focus on understanding an intervention's mechanism of action - why or how an intervention was effective. We believe changes are needed to four types of research. First, outcome evaluations should draw on programme theory. Second, process evaluations should aim to understand interventions' mechanism of action, rather than simply 'what happened'. Third, small scoping studies should be conducted in new settings, to explore how to enact identified mechanisms. Finally, innovative synthesis methods are required, in order to identify mechanisms of action where there is a lack of existing process evaluations.


Assuntos
Jornalismo Médico , Avaliação de Programas e Projetos de Saúde/métodos , Projetos de Pesquisa , Humanos , Escrita Médica
18.
Nucleic Acids Res ; 47(21): 11403-11417, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31598697

RESUMO

Exposure to harmful conditions such as radiation and desiccation induce oxidative stress and DNA damage. In radiation-resistant Deinococcus bacteria, the radiation/desiccation response is controlled by two proteins: the XRE family transcriptional repressor DdrO and the COG2856 metalloprotease IrrE. The latter cleaves and inactivates DdrO. Here, we report the biochemical characterization and crystal structure of DdrO, which is the first structure of a XRE protein targeted by a COG2856 protein. DdrO is composed of two domains that fold independently and are separated by a flexible linker. The N-terminal domain corresponds to the DNA-binding domain. The C-terminal domain, containing three alpha helices arranged in a novel fold, is required for DdrO dimerization. Cleavage by IrrE occurs in the loop between the last two helices of DdrO and abolishes dimerization and DNA binding. The cleavage site is hidden in the DdrO dimer structure, indicating that IrrE cleaves DdrO monomers or that the interaction with IrrE induces a structural change rendering accessible the cleavage site. Predicted COG2856/XRE regulatory protein pairs are found in many bacteria, and available data suggest two different molecular mechanisms for stress-induced gene expression: COG2856 protein-mediated cleavage or inhibition of oligomerization without cleavage of the XRE repressor.


Assuntos
Deinococcus , Proteínas Repressoras/química , Estresse Fisiológico/genética , Estresse Fisiológico/efeitos da radiação , Fatores de Transcrição/química , Sequência de Aminoácidos , Cristalografia por Raios X , Dano ao DNA , Deinococcus/enzimologia , Deinococcus/genética , Deinococcus/metabolismo , Deinococcus/efeitos da radiação , Regulação Bacteriana da Expressão Gênica/efeitos da radiação , Metaloproteases/química , Metaloproteases/genética , Metaloproteases/metabolismo , Modelos Moleculares , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas Repressoras/genética , Fatores de Transcrição/genética
20.
J Exp Bot ; 70(18): 5003-5016, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31128069

RESUMO

Plant 2-Cys peroxiredoxins (2-CysPRXs) are abundant plastidial thiol-peroxidases involved in key signaling processes such as photosynthesis deactivation at night. Their functions rely on the redox status of their two cysteines and on the enzyme quaternary structure, knowledge of which remains poor in plant cells. Using ex vivo and biochemical approaches, we thoroughly characterized the 2-CysPRX dimer/monomer distribution, hyperoxidation level, and thiol content in Arabidopsis, barley, and potato in relation to the light cycle. Our data reveal that the enzyme hyperoxidization level and its distribution as a dimer and monomer vary through the light cycle in a species-dependent manner. A differential susceptibility to hyperoxidation was observed for the two Arabidopsis 2-CysPRX isoforms and among the proteins of the three species, and was associated to sequence variation in hyperoxidation resistance motifs. Alkylation experiments indicate that only a minor fraction of the 2-CysPRX pool carries one free thiol in the three species, and that this content does not change during the light period. We conclude that most plastidial 2-CysPRX forms are oxidized and propose that there is a species-dependent variability in their functions since dimer and hyperoxidized forms fulfill distinct roles regarding direct oxidation of partners and signal transmission.


Assuntos
Arabidopsis/metabolismo , Hordeum/metabolismo , Peroxirredoxinas/metabolismo , Fotoperíodo , Proteínas de Plantas/metabolismo , Solanum tuberosum/metabolismo , Cisteína/química , Oxirredução , Especificidade da Espécie
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