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1.
Nature ; 632(8025): 557-563, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39048828

RESUMO

Anthropogenic activities have substantially enhanced the loadings of reactive nitrogen (Nr) in the Earth system since pre-industrial times1,2, contributing to widespread eutrophication and air pollution3-6. Increased Nr can also influence global climate through a variety of effects on atmospheric and land processes but the cumulative net climate effect is yet to be unravelled. Here we show that anthropogenic Nr causes a net negative direct radiative forcing of -0.34 [-0.20, -0.50] W m-2 in the year 2019 relative to the year 1850. This net cooling effect is the result of increased aerosol loading, reduced methane lifetime and increased terrestrial carbon sequestration associated with increases in anthropogenic Nr, which are not offset by the warming effects of enhanced atmospheric nitrous oxide and ozone. Future predictions using three representative scenarios show that this cooling effect may be weakened primarily as a result of reduced aerosol loading and increased lifetime of methane, whereas in particular N2O-induced warming will probably continue to increase under all scenarios. Our results indicate that future reductions in anthropogenic Nr to achieve environmental protection goals need to be accompanied by enhanced efforts to reduce anthropogenic greenhouse gas emissions to achieve climate change mitigation in line with the Paris Agreement.

2.
Nature ; 620(7976): 1013-1017, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37438527

RESUMO

Pesticides are ubiquitous environmental pollutants negatively affecting ecosystem and human health1,2. About 3 Tg of pesticides are used annually in agriculture to protect crops3. How much of these pesticides remain on land and reach the aquifer or the ocean is uncertain. Monitoring their environmental fate is challenging, and a detailed picture of their mobility in time and space is largely missing4. Here, we develop a process-based model accounting for the hydrology and biogeochemistry of the 92 most used agricultural pesticide active substances to assess their pathways through the principal catchments of the world and draw a near-present picture of the global land and river budgets, including discharge to oceans. Of the 0.94 Tg net annual pesticide input in 2015 used in this study, 82% is biologically degraded, 10% remains as residue in soil and 7.2% leaches below the root zone. Rivers receive 0.73 Gg of pesticides from their drainage at a rate of 10 to more than 100 kg yr-1 km-1. By contrast to their fate in soil, only 1.1% of pesticides entering rivers are degraded along streams, exceeding safety levels (concentrations >1 µg l-1) in more than 13,000 km of river length, with 0.71 Gg of pesticide active ingredients released to oceans every year. Herbicides represent the prevalent pesticide residue on both land (72%) and river outlets (62%).


Assuntos
Agricultura , Monitoramento Ambiental , Poluentes Ambientais , Oceanos e Mares , Praguicidas , Rios , Solo , Humanos , Ecossistema , Praguicidas/análise , Rios/química , Solo/química , Poluentes Químicos da Água/análise , Água do Mar/química , Herbicidas/análise , Poluentes do Solo/análise , Poluentes Ambientais/análise
3.
Nurs Ethics ; : 9697330231222595, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38155364

RESUMO

BACKGROUND: Caring practice begins with awareness of the suffering of patients in a given context. Understanding the interrelationship between the perceived ethical climate of the clinical environment and the ethical sensitivity and caring efficacy of nurses is crucial for strengthening the caring competency of nurses. RESEARCH AIM: This study aimed to examine the associations between the ethical climate of the clinical environment and the ethical sensitivity and caring efficacy of nurses and to investigate the mediating effect of ethical sensitivity on the association between ethical climate and caring efficacy. RESEARCH DESIGN: This was a quantitative study with a cross-sectional descriptive correlational design. The participants completed an online survey that measured the ethical climate, ethical sensitivity and caring efficacy using the Hospital Ethical Climate Survey, Moral Sensitivity Questionnaire-Revised and Caring Efficacy Scale, respectively. PARTICIPANTS AND RESEARCH CONTEXT: The study recruited 293 nurses from two general hospitals that provided acute in-patient and extended care in Hong Kong. ETHICAL CONSIDERATIONS: Ethical approval was obtained from the ethics committee of the university and the hospitals involved. Written consent was obtained from the participants. RESULTS: Ethical climate was associated with caring efficacy (ß = 0.340, p < .001) and ethical sensitivity (ß = 0.197, p < .001). After adjusting for ethical climate, ethical sensitivity was associated with caring efficacy (ß = 0.860, p < .001). Ethical sensitivity showed a significant mediating effect on the association between ethical climate and caring efficacy (indirect effect = 0.169, 95% confidence interval: 0.097 to 0.261), which accounted for 50% of the total effect. CONCLUSIONS: The study reveals the complex and interwoven relationship between contextual and personal factors that affect nurses' caring efficacy from an ethical perspective. It provides insights into the significant roles of ethical climate and ethical sensitivity in strengthening caring efficacy. The results suggest theoretical and clinical implications for professionalisation.

4.
Stress ; 24(2): 168-180, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33322989

RESUMO

Over the years, it has become increasingly clear that males and females respond differently towards environmental stressors, highlighting the importance of including both sexes when studying the effects of stress. This study aims to provide further insight into the detailed consequences of exposing female mice to 21 days of chronic social defeat stress (CSDS). We used a protocol that relies on the ability of odorants and pheromones in male urine to trigger male mouse aggressive behavior. Collected male C57Bl/6n urine was applied to female C57Bl/6n mice who were then attacked by a novel male CD1 mouse each day according to the CDSD protocol. Control females were pair-housed and handled daily. Physiological, neuroendocrine and behavioral changes were evaluated during the experiment. CSDS exposure resulted in number of physiological changes, such as body weight gain, enlarged adrenals and reduced thymus weight, exaggerated HPA-axis negative feedback and increased anxiety-like behavior. However, no generalized social avoidance behavior was observed. This study provides important insights in the physiological, neuroendocrine and behavioral responses of female mice to CSDS, which are partially dependent on estrous cycle stage. This protocol will allow direct comparison of male and female responses to CSDS and enable sex-specific study of mechanisms underlying individual stress resilience.Lay summaryIn this study we found that there are differences in the way that female and male mice respond towards chronic social stress conditions when it comes to behavior and hormonal changes.


Assuntos
Derrota Social , Estresse Psicológico , Animais , Aprendizagem da Esquiva , Comportamento Animal , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Comportamento Social
5.
BMC Nurs ; 20(1): 81, 2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34022878

RESUMO

BACKGROUND: Developing students' generic capabilities is a major goal of university education as it can help to equip students with life-long learning skills and promote holistic personal development. However, traditional didactic teaching has not been very successful in achieving this aim. Kember and Leung's Teaching and Learning Model suggests an interactive learning environment has a strong impact on developing students' generic capabilities. Metacognitive awareness is also known to be related to generic capability development. This study aimed to assess changes on the development of generic capabilities and metacognitive awareness after the introduction of active learning strategy among nursing students. METHODS: This study adopted a quasi-experimental single group, matched pre- and posttest design. It was conducted in a school of nursing at a university in Hong Kong. Active learning approaches included the flipped classroom (an emphasis on pre-reading) and enhanced lectures (the breaking down of a long lecture into several mini-lectures and supplemented by interactive learning activities) were introduced in a foundational nursing course. The Capabilities Subscale of the Student Engagement Questionnaire and the Metacognitive Awareness Inventory were administered to two hundred students at the start (T0) and at the end of the course (T1). A paired t-test was performed to examine the changes in general capabilities and metacognitive awareness between T0 and T1. RESULTS: A total of 139 paired pre- and post-study responses (69.5 %) were received. Significant improvements were observed in the critical thinking (p < 0.001), creative thinking (p = 0.03), problem-solving (p < 0.001) and communication skills (p = 0.04) with the implementation of active learning. Significant changes were also observed in knowledge of cognition (p < 0.001) and regulation of cognition (p < 0.001) in the metacognitive awareness scales. CONCLUSIONS: Active learning is a novel and effective teaching approach that can be applied in the nursing education field. It has great potential to enhance students' development of generic capabilities and metacognitive awareness.

6.
Environ Sci Technol ; 54(17): 10399-10410, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32786599

RESUMO

Trifluralin is a widely used dinitroaniline herbicide, which can persist in the environment and has substantial ecotoxicity, especially to aquatic organisms. Trifluralin is very insoluble in water (0.22 mg/L at 20 °C) and highly volatile (vapor pressure of 6.7 mPa at 20 °C); these physicochemical properties determine a large part of its environmental fate, which includes rapid loss from soils if surface-applied, strong binding to soil organic matter, and negligible leaching into water. The trifluralin structure contains a tertiary amino group, two nitro-groups and a trifluoromethyl- group. Despite the strongly xenobiotic character of some of these substituents, biodegradation of trifluralin does occur, and pure cultures of bacteria and fungi capable of partially degrading the molecule either by dealkylation or nitro-group reduction have been identified. There are many unanswered questions about the environmental fate and metabolism of this herbicide; the genes and enzymes responsible for biodegradation are largely unknown, the relative roles of abiotic processes vs growth-linked biodegradation vs cometabolism are unresolved, and the impact of different environmental factors on the rates and extents of biodegradation are not clear. Here, we summarize the relevant literature on the persistence and environmental fate of trifluralin with a focus on biodegradation pathways and mechanisms, and we identify the current major knowledge gaps for future research.


Assuntos
Herbicidas , Poluentes do Solo , Bactérias , Biodegradação Ambiental , Fungos , Herbicidas/análise , Poluentes do Solo/análise , Trifluralina/análise
7.
J Adv Nurs ; 75(6): 1360-1369, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30697793

RESUMO

AIM: To examine the effect of a video-supported nurse-led advance care planning to frail geriatric patients on end-of-life decision-making outcomes in patients and their carers. DESIGN: This is a double-blinded randomized controlled trial with parallel arms. METHODS: The protocol was approved by the Institutional Review Board of the participating hospital on 1 August 2018. Frail elders and their carer if any are enrolled during hospitalization, and undergo randomization after discharged. The intervention group receives a 2-week video-supported nurse-led advance care planning programme (N = 149) while the control group receives a 2-week health education program at home (N = 149). Follow-up surveys via telephone at 1 and 6 months measure outcomes regarding end-of-life decision-making from both the patients and the carers. CONCLUSION: Advance care planning discussion is to understand patient's values, preferences and treatment for care on their anticipation of future deterioration. Treatment options for end-of-life care may not be well-received especially elders because in the discussion process, technical medical terms are presented in an abstract, hypothetical way that are hard to understand. The present study aims to evaluate the effect of a nurse-led advance care planning supplementing with a video showing end-of-life treatment options to promote end-of-life care decision-making among frail geriatric patients. IMPACT: The results will help identify effective elements of advance care planning and inform the development of an evidence?based structured advance care planning intervention in response to the need for quality end-of-life care. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-17012341.


Assuntos
Planejamento Antecipado de Cuidados/organização & administração , Cuidadores/educação , Idoso Fragilizado/psicologia , Papel do Profissional de Enfermagem/psicologia , Educação de Pacientes como Assunto/métodos , Assistência Terminal/psicologia , Gravação em Vídeo , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidadores/psicologia , Comunicação , Tomada de Decisões , Família/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Relações Enfermeiro-Paciente , Inquéritos e Questionários
8.
Nurs Health Sci ; 21(1): 85-92, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30156371

RESUMO

Caring seems to be undervalued in the technologically-advanced and fast-paced clinical environment. To improve nursing practice, it is important to understand the meanings of caring to nurses. The aim of the present study was to explore nurses' perspectives of caring in the contemporary clinical environment. A focus group exploration was employed. Multiple perspectives were elicited from 80 nurses with different backgrounds: nursing students, nurse educators, registered nurses, advanced clinical nurses, and nurse executives. The qualitative data were analyzed using thematic analysis. Nurses' understanding of caring could be described using four Es: engaging in reciprocal relationships, embracing the essence of caring, engendering instances of caring, and embodying caring in practice. Participants described nurses as having the dual roles of caregiver and care recipient. The centrality of caring in nursing and the necessity of caring for caregivers were emphasized. The nurses also described various caring behaviors in daily practice. The present study revealed that nurses need empowerment to sustain their compassion. The findings provide new insights, which indicate that the revitalization of nurses' passion for caring in the contemporary clinical environment should begin with caring for caregivers.


Assuntos
Empatia , Enfermeiras e Enfermeiros/psicologia , Enfermeiras e Enfermeiros/normas , Adulto , Atitude do Pessoal de Saúde , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto/métodos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa
9.
Int J Nurs Pract ; 24(4): e12658, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29642280

RESUMO

AIM: The study aimed to assess the feasibility and acceptability of an innovative tablet-assisted self-reported symptom assessment among newly diagnosed lung cancer patients. BACKGROUND: Routine symptom assessment for lung cancer patients in a fast-paced clinical environment is demanding. Mobile health technology offers a potential platform for symptom assessment and paves the way for tailored self-care intervention. DESIGN: A feasibility study using a mixed method design. METHOD: A convenience sample of 10 newly diagnosed lung cancer patients used tablet personal computers to self-report common symptoms: dyspnoea, fatigue, pain, and anxiety. A nurse reviewed the assessment results and provided tailored educational interventions. Acceptability was evaluated by the Electronic Self-Report Assessment-Cancer. Semi-structured interviews were conducted to explore the patients' perceptions of this symptom assessment method. Data were collected from January to March 2016. RESULTS: An Electronic Self-Report Assessment-Cancer mean score of 23.5 (SD 2.7) showed moderate acceptance of the assessment method. Participants found this approach user-friendly and helpful in identifying their symptoms and they gained awareness and better understanding of them. CONCLUSION: Tablet-assisted symptom assessment is a feasible method that can be further tested in busy clinical settings to assess symptom burden and identify individual needs for tailoring symptom management plans.


Assuntos
Neoplasias Pulmonares/complicações , Microcomputadores , Autorrelato , Avaliação de Sintomas , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Dor do Câncer/etiologia , Dispneia/etiologia , Fadiga/etiologia , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/enfermagem , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos de Amostragem
10.
Int J Cancer ; 139(3): 664-72, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-26990817

RESUMO

Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed.


Assuntos
Biomarcadores Tumorais , Linfonodos/patologia , Melanoma/genética , Melanoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Recidiva , Biópsia de Linfonodo Sentinela , Adulto Jovem
12.
Int J Mol Sci ; 17(3): 286, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-26927069

RESUMO

Lung cancer is ranked first worldwide as one of the main cancers in terms of prevalence and mortality rate. The development of effective treatment strategies against lung cancer is therefore of paramount importance. Traditionally, chemotherapy was employed in the treatment of various cancers. However, the non-specific nature of the actions of chemotherapeutic drugs and the potential for tumors to develop resistance to these drugs may render chemotherapy a less favorable option for cancer treatment. Immunotherapy provides an alternative strategy for this purpose. It involves the utilization of the immune system and the immune effector cells to elicit an immune response to the tumors, thereby eliminating them. Strategies include the administration of pro-inflammatory cytokines for immune stimulation, the removal of immunological checkpoints using monoclonal antibodies, and the use of cancer vaccines to enhance immunity against tumors. This article summarizes the above strategies, highlights the reasons why immunotherapy is superior to chemotherapy for the purpose of tumor removal, and reviews the recent clinical studies comparing the clinical outcomes of patients undergoing immunotherapy and chemotherapy. The article also describes advances in immunotherapeutic strategies for the treatment of lung cancer.


Assuntos
Imunoterapia/métodos , Neoplasias Pulmonares/terapia , Animais , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Humanos , Neoplasias Pulmonares/imunologia
13.
Soft Matter ; 11(47): 9150-9, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26414181

RESUMO

There has been growing interest in using the fractal dimension to study the hierarchical structures of soft materials after realising that fractality is an important property of natural and engineered materials. This work presents a method to quantify the internal architecture and the space-filling capacity of granular fractal aggregates by reconstructing the three-dimensional capacity dimension from their two-dimensional optical projections. Use is made of the light intensity of the two-dimensional aggregate images to describe the aggregate surface asperities (quantified by the perimeter-based fractal dimension) and the internal architecture (quantified by the capacity dimension) within a mathematical framework. This method was tested on control aggregates of diffusion-limited (DLA), cluster-cluster (CCA) and self-correlated (SCA) types, stereolithographically-fabricated aggregates, and experimentally-acquired natural sedimentary aggregates. Statistics of the reconstructed capacity dimension featured correlation coefficients R ≥ 98%, residuals NRMSE ≤ 10% and percent errors PE ≤ 4% as compared to controls, and improved earlier approaches by up to 50%.


Assuntos
Modelos Teóricos , Materiais Biocompatíveis/química , Difusão , Imagem Óptica
14.
Sci Data ; 11(1): 413, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649341

RESUMO

CROPGRIDS is a comprehensive global geo-referenced dataset providing area information for 173 crops for the year 2020, at a resolution of 0.05° (about 5.6 km at the equator). It represents a major update of the Monfreda et al. (2008) dataset (hereafter MRF), the most widely used geospatial dataset previously available, covering 175 crops with reference year 2000 at 10 km spatial resolution. CROPGRIDS builds on information originally provided in MRF and expands it using 27 selected published gridded datasets, subnational data of 52 countries obtained from National Statistical Offices, and the 2020 national-level statistics from FAOSTAT, providing more recent harvested and crop (physical) areas for 173 crops at regional, national, and global levels. The CROPGRIDS data advance the current state of knowledge on the spatial distribution of crops, providing useful inputs for modelling studies and sustainability analyses relevant to national and international processes.


Assuntos
Produtos Agrícolas
15.
Heliyon ; 10(9): e30039, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707455

RESUMO

Aim: To determine the effect of simulation-based Zoom learning (SBZL) on perceived capabilities and clinical decision-making skills among undergraduate nursing students and to explore experiences of the instructors and students participating in SBZL. Background: Nursing is a practice profession and students acquire clinical decision-making skills in clinical settings. However, the COVID-19 pandemic has disrupted conventional clinical learning activities. In this study, the outcomes of implementing SBZL in an undergraduate programme to support students' clinical learning were examined. Design: A mixed methods design was employed. Methods: This study recruited 195 final-year students to participate in the SBZL programme, which was developed based on the NLN Jeffries Simulation Theory to guide its design, implementation and evaluation. Case scenarios were developed and simulated through Zoom. Students' perceived capabilities, perceptions of the learning environment and clinical decision-making skills were assessed before and after SBZL. A historical control group of 226 previous final year students who had received a clinical practicum was included for comparison. Semi-structured interviews were conducted with 11 instructors and 19 students to explore their experiences of participating in SBZL. Results: A total of 102 students completed the post-SBZL questionnaire. An increase in perceived creative thinking (mean difference = 0.24, p < 0.001) was observed post-SBZL. After SBZL, the perceptions of the learning environment were significantly improved. However, the SBZL group demonstrated lower perceived problem-solving capability than the control group (mean difference = 0.14, p = 0.007). Clinical decision-making was significantly improved in the SBZL group than in the control group (p < 0.001). Both the instructors and students reported positive experiences with SBZL, and highlighted challenges and factors for improving its implementation. Conclusions: SBZL showed improvement in perceived creative thinking, perceptions of the learning environment and clinical decision-making. This innovative teaching and learning method can be valuable for nursing education in various regions to prepare students for real-life roles. Tweetable abstract: Simulation-based Zoom learning is better than traditional teaching in improving clinical decision-making skills among undergraduate nursing students.

16.
Nat Commun ; 15(1): 2635, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528004

RESUMO

High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. Here we show that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1ß release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in male mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1ß release, contributing to an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of male and female postmortem human brains demonstrate that SA is hyperactivated in Alzheimer's disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer's disease, providing mechanistic insight into the biology of neuroinflammation.


Assuntos
Doença de Alzheimer , Autofagia , Proteínas Cromossômicas não Histona , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Animais , Feminino , Humanos , Masculino , Camundongos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Autofagia/genética , Proteínas Cromossômicas não Histona/metabolismo , Citocinas/metabolismo , Inflamassomos/metabolismo , Microglia/metabolismo , Doenças Neuroinflamatórias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
17.
bioRxiv ; 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37066393

RESUMO

High levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. We demonstrate that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1ß release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1ß release, initiating an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D (GSDMD)-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of postmortem brains demonstrate that SA is hyperactivated in Alzheimer's disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer's disease, providing new mechanistic insight into the biology of neuroinflammation.

18.
Rapid Commun Mass Spectrom ; 26(4): 430-42, 2012 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-22279019

RESUMO

RATIONALE: Earlier experiments demonstrated that isotopic effects during nitrification, denitrification and dissimilatory nitrate reduction can be affected by high (15) N contents. These findings call into question whether the reaction parameters (rate constants and Michaelis-Menten concentrations) are function of δ(15) N values, and if these can also lead to significant effects on the bulk reaction rate. METHODS: Five experiments at initial δ(15) N-NO(3) (-) values ranging from 0‰ to 1700‰ were carried out in a recent study using elemental analyser, gas chromatography, and mass spectrometry techniques coupled at various levels. These data were combined here with kinetic equations of isotopologue speciation and fractionation. Our approach specifically addressed the combinatorial nature of reactions involving labeled atoms and explicitly described substrate competition and time-dependent isotopic effects. RESULTS: With the method presented here, we determined with relatively high accuracy that the reaction rate constants increased linearly up to 270% and the Michaelis-Menten concentrations decreased linearly by about 30% over the tested δ(15) N-NO(3) (-) values. Because the parameters were found to depend on the (15) N enrichment level, we could determine that increasing δ(15) N-NO(3) (-) values caused a decrease in bulk nitrification, denitrification and dissimilatory nitrate reduction rates by 50% to 60%. CONCLUSIONS: We addressed a method that allowed us to quantify the effect of substrate isotopic enrichment on the reaction kinetics. Our results enable us to reject the assumption of constant reaction parameters. The implications of δ-dependent (variable) reaction parameters extend beyond the study-case analysed here to all instances in which high and variable isotopic enrichments occur.

19.
Sci Total Environ ; 838(Pt 1): 156011, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35595148

RESUMO

Microplastic fibres are the most abundant microplastics in waterways worldwide. The settling of fibres is distinct from other particles because of their aspect ratio and shape. In this paper, we test the hypothesis that length, curliness, and settling orientation control the settling velocity of microplastic fibres in a suite of laboratory experiments. Using a Particle Tracking Velocimetry method, we measured the settling velocity of 683 polyester microplastic fibres of 1 to 4 mm in length. Experimental findings support our hypothesis that for microplastic fibre longer than 1 mm, changing settling orientation from horizontal to vertical can increase 1.7 times the settling velocity. Fibre curliness can significantly reduce the settling velocity, where a curly fibre 1.3 times longer than a straight fibre can settle 1.75 times slower. In contrast, short microplastic fibres (less than 1 mm) mostly settle horizontally, and their settling velocity is unaffected by curliness. The drag force exerting on settling microplastic fibres was analysed, and the sphere-equivalent diameter was found to be a good representation of microplastic fibre size to predict the drag coefficient. Measured settling velocity ranges between 0.1 and 0.55 mm/s and exhibits a slight increase with the increasing length of the fibres. This low-velocity range raises concerns that microplastic fibres can favour biological flocculation, form clustered aggregates with microorganisms, feed aquatic organisms and cause bioaccumulation at higher trophic levels.


Assuntos
Microplásticos , Poluentes Químicos da Água , Monitoramento Ambiental/métodos , Tamanho da Partícula , Plásticos/análise , Água/análise , Poluentes Químicos da Água/análise
20.
Sci Data ; 8(1): 263, 2021 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615885

RESUMO

We introduce here SOIL-WATERGRIDS, a new dataset of dynamic changes in soil moisture and depth of water table over 45 years from 1970 to 2014 globally resolved at 0.25 × 0.25 degree resolution (about 30 × 30 km at the equator) along a 56 m deep soil profile. SOIL-WATERGRIDS estimates were obtained using the BRTSim model instructed with globally gridded soil physical and hydraulic properties, land cover and use characteristics, and hydrometeorological variables to account for precipitation, ecosystem-specific evapotranspiration, snowmelt, surface runoff, and irrigation. We validate our estimates against independent observations and re-analyses of the soil moisture, water table depth, wetland occurrence, and runoff. SOIL-WATERGRIDS brings into a single product the monthly mean water saturation at three depths in the root zone and the depth of the highest and lowest water tables throughout the reference period, their long-term monthly averages, and data quality. SOIL-WATERGRIDS can therefore be used to analyse trends in water availability for agricultural abstraction, assess the water balance under historical weather patterns, and identify water stress in sensitive managed and unmanaged ecosystems.

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