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1.
Nature ; 585(7826): 545-550, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32968258

RESUMO

To constrain global warming, we must strongly curtail greenhouse gas emissions and capture excess atmospheric carbon dioxide1,2. Regrowing natural forests is a prominent strategy for capturing additional carbon3, but accurate assessments of its potential are limited by uncertainty and variability in carbon accumulation rates2,3. To assess why and where rates differ, here we compile 13,112 georeferenced measurements of carbon accumulation. Climatic factors explain variation in rates better than land-use history, so we combine the field measurements with 66 environmental covariate layers to create a global, one-kilometre-resolution map of potential aboveground carbon accumulation rates for the first 30 years of natural forest regrowth. This map shows over 100-fold variation in rates across the globe, and indicates that default rates from the Intergovernmental Panel on Climate Change (IPCC)4,5 may underestimate aboveground carbon accumulation rates by 32 per cent on average and do not capture eight-fold variation within ecozones. Conversely, we conclude that maximum climate mitigation potential from natural forest regrowth is 11 per cent lower than previously reported3 owing to the use of overly high rates for the location of potential new forest. Although our data compilation includes more studies and sites than previous efforts, our results depend on data availability, which is concentrated in ten countries, and data quality, which varies across studies. However, the plots cover most of the environmental conditions across the areas for which we predicted carbon accumulation rates (except for northern Africa and northeast Asia). We therefore provide a robust and globally consistent tool for assessing natural forest regrowth as a climate mitigation strategy.


Assuntos
Sequestro de Carbono , Carbono/metabolismo , Agricultura Florestal/estatística & dados numéricos , Agricultura Florestal/tendências , Florestas , Mapeamento Geográfico , Árvores/crescimento & desenvolvimento , Árvores/metabolismo , Conservação dos Recursos Naturais , Coleta de Dados , Recuperação e Remediação Ambiental , Aquecimento Global/prevenção & controle , Internacionalidade , Cinética
2.
Eur J Immunol ; 53(7): e2250056, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37058370

RESUMO

TLRs engage numerous adaptor proteins and signaling molecules, enabling a complex series of post-translational modifications (PTMs) to mount inflammatory responses. TLRs themselves are post-translationally modified following ligand-induced activation, with this being required to relay the full spectrum of proinflammatory signaling responses. Here, we reveal indispensable roles for TLR4 Y672 and Y749 phosphorylation in mounting optimal LPS-inducible inflammatory responses in primary mouse macrophages. LPS promotes phosphorylation at both tyrosine residues, with Y749 phosphorylation being required for maintenance of total TLR4 protein levels and Y672 phosphorylation exerting its pro-inflammatory effects more selectively by initiating ERK1/2 and c-FOS phosphorylation. Our data also support a role for the TLR4-interacting membrane proteins SCIMP and the SYK kinase axis in mediating TLR4 Y672 phosphorylation to permit downstream inflammatory responses in murine macrophages. The corresponding residue in human TLR4 (Y674) is also required for optimal LPS signaling responses. Our study, thus, reveals how a single PTM on one of the most widely studied innate immune receptors orchestrates downstream inflammatory responses.


Assuntos
Citocinas , Lipopolissacarídeos , Humanos , Animais , Camundongos , Fosforilação , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Receptor 4 Toll-Like , Tirosina/metabolismo , Tirosina/farmacologia , Macrófagos
3.
Curr Allergy Asthma Rep ; 24(1): 1-9, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153610

RESUMO

PURPOSE OF REVIEW: Pollen is enormously important to the human experience. As pollen became germane to human health in the late nineteenth century, methods for pollen collection and measurement were developed. Techniques were standardized and pollen counting networks were established in many parts of the world during the middle to late part of the twentieth century. With some notable exceptions, the technology of the 1950s and 1960s is presently employed to create the current pollen counting networks. Pollen counting networks in the past faced substantial challenges. Pollen counting networks using the same technology as the past face the same challenges. RECENT FINDINGS: As we move into the twenty-first century, automated pollen counting technology enables pollen counting networks to be robust, available, scalable, self-perpetuating, and able to meet modern demands. Automated pollen measurement networks present a promising path towards a more informed, data-driven, and effective approach to managing allergens, improving crop yields, and minimizing human suffering caused by pollen. By empowering individuals with comprehensive pollen data, a feat not possible with manual counting, we can help people make informed decisions and take proactive measures to minimize exposure to allergens and improve their well-being.


Assuntos
Monitoramento Ambiental , Pólen , Humanos , Monitoramento Ambiental/métodos , Alérgenos , Tecnologia
4.
J Biol Chem ; 298(5): 101857, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35337798

RESUMO

Innate immune signaling by Toll-like receptors (TLRs) involves receptor phosphorylation, which helps to shape and drive key inflammatory outputs, yet our understanding of the kinases and mechanisms that mediate TLR phosphorylation is incomplete. Spleen tyrosine kinase (Syk) is a nonreceptor protein tyrosine kinase, which is known to relay adaptive and innate immune signaling, including from TLRs. However, TLRs do not contain the conserved dual immunoreceptor tyrosine-based activation motifs that typically recruit Syk to many other receptors. One possibility is that the Syk-TLR association is indirect, relying on an intermediary scaffolding protein. We previously identified a role for the palmitoylated transmembrane adapter protein SCIMP in scaffolding the Src tyrosine kinase Lyn, for TLR phosphorylation, but the role of SCIMP in mediating the interaction between Syk and TLRs has not yet been investigated. Here, we show that SCIMP recruits Syk in response to lipopolysaccharide-mediated TLR4 activation. We also show that Syk contributes to the phosphorylation of SCIMP and TLR4 to enhance their binding. Further evidence pinpoints two specific phosphorylation sites in SCIMP critical for its interaction with Syk-SH2 domains in the absence of immunoreceptor tyrosine-based activation motifs. Finally, using inhibitors and primary macrophages from SCIMP-/- mice, we confirm a functional role for SCIMP-mediated Syk interaction in modulating TLR4 phosphorylation, signaling, and cytokine outputs. In conclusion, we identify SCIMP as a novel, immune-specific Syk scaffold, which can contribute to inflammation through selective TLR-driven inflammatory responses.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Membrana , Quinase Syk , Receptor 4 Toll-Like , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Macrófagos/enzimologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Fosforilação , Quinase Syk/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Tirosina/metabolismo , Quinases da Família src/metabolismo
5.
Biochem Soc Trans ; 50(5): 1341-1352, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36281999

RESUMO

Extracellular signal-related kinases 1 and 2 (ERK1/2) are the final components of the mitogen-activated protein kinase (MAPK) phosphorylation cascade, an integral module in a diverse array of signalling pathways for shaping cell behaviour and fate. More recently, studies have shown that ERK1/2 plays an essential role downstream of immune receptors to elicit inflammatory gene expression in response to infection and cell or tissue damage. Much of this work has studied ERK1/2 activation in Toll-like receptor (TLR) pathways, providing mechanistic insights into its recruitment, compartmentalisation and activation in cells of the innate immune system. In this review, we summarise the typical activation of ERK1/2 in growth factor receptor pathways before discussing its known roles in immune cell signalling with a focus downstream of TLRs. We examine emerging research uncovering evidence of dysfunctional ERK1/2 signalling in inflammatory diseases and discuss the potential therapeutic benefit of targeting ERK1/2 pathways in inflammation.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular , Sistema de Sinalização das MAP Quinases , Humanos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Transdução de Sinais , Fosforilação , Inflamação
6.
Glob Chang Biol ; 28(21): 6293-6317, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36047436

RESUMO

A globally relevant and standardized taxonomy and framework for consistently describing land cover change based on evidence is presented, which makes use of structured land cover taxonomies and is underpinned by the Driver-Pressure-State-Impact-Response (DPSIR) framework. The Global Change Taxonomy currently lists 246 classes based on the notation 'impact (pressure)', with this encompassing the consequence of observed change and associated reason(s), and uses scale-independent terms that factor in time. Evidence for different impacts is gathered through temporal comparison (e.g., days, decades apart) of land cover classes constructed and described from Environmental Descriptors (EDs; state indicators) with pre-defined measurement units (e.g., m, %) or categories (e.g., species type). Evidence for pressures, whether abiotic, biotic or human-influenced, is similarly accumulated, but EDs often differ from those used to determine impacts. Each impact and pressure term is defined separately, allowing flexible combination into 'impact (pressure)' categories, and all are listed in an openly accessible glossary to ensure consistent use and common understanding. The taxonomy and framework are globally relevant and can reference EDs quantified on the ground, retrieved/classified remotely (from ground-based, airborne or spaceborne sensors) or predicted through modelling. By providing capacity to more consistently describe change processes-including land degradation, desertification and ecosystem restoration-the overall framework addresses a wide and diverse range of local to international needs including those relevant to policy, socioeconomics and land management. Actions in response to impacts and pressures and monitoring towards targets are also supported to assist future planning, including impact mitigation actions.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Monitoramento Ambiental , Humanos
7.
J Cell Sci ; 133(5)2019 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-31889021

RESUMO

Toll-like receptors (TLRs) are danger-sensing receptors that typically propagate self-limiting inflammatory responses, but can unleash uncontrolled inflammation in non-homeostatic or disease settings. Activation of TLRs by pathogen- and/or host-derived stimuli triggers a range of signalling and transcriptional pathways to programme inflammatory and anti-microbial responses, including the production of a suite of inflammatory cytokines and other mediators. Multiple sorting and signalling adaptors are recruited to receptor complexes on the plasma membrane or endosomes where they act as scaffolds for downstream signalling kinases and effectors at these sites. So far, seven proximal TLR adaptors have been identified: MyD88, MAL, TRIF (also known as TICAM1), TRAM (TICAM2), SARM (SARM1), BCAP (PIK3AP1) and SCIMP. Most adaptors tether directly to TLRs through homotypic Toll/interleukin-1 receptor domain (TIR)-TIR interactions, whereas SCIMP binds to TLRs through an atypical TIR-non-TIR interaction. In this Review, we highlight the key roles for these adaptors in TLR signalling, scaffolding and receptor sorting and discuss how the adaptors thereby direct the differential outcomes of TLR-mediated responses. We further summarise TLR adaptor regulation and function, and make note of human diseases that might be associated with mutations in these adaptors.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Receptores de Interleucina-1/metabolismo , Transdução de Sinais , Receptores Toll-Like/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Citocinas/genética , Citocinas/metabolismo , Humanos , Ligação Proteica , Transporte Proteico , Receptores de Interleucina-1/genética , Receptores Toll-Like/genética
8.
J Pers ; 89(1): 23-34, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32453864

RESUMO

OBJECTIVE: Despite a narrative of post-traumatic growth and resilience, research reliably demonstrating positive character development following adversity has proved elusive. In the current study, we examined changes in character strengths in Army soldiers deploying for the first time. METHOD: The sample was comprised of 212,386 Army soldiers (Mage  = 26.5 years old, SD = 7.13; 70.8% White) who were deploying for the first time. Character strengths were assessed once before and up to three times following soldiers' return from deployment. RESULTS: We found evidence for two classes of change-a resilient class ("stable high") and a declining class ("persistent low"). Most soldiers were resilient-they had high levels of character strengths prior to deployment and changed very little across the deployment cycle. Approximately 40% of soldiers started with lower character and experienced initial declines post-deployment, from which they experienced no more than small gains over time. CONCLUSIONS: Character strengths were highly stable across the deployment transition but some soldiers experienced initial declines from which they never fully rebounded. The findings are discussed in the context of the mechanisms that drive character development.


Assuntos
Militares , Adulto , Humanos
9.
J Pers ; 89(1): 145-165, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32897574

RESUMO

OBJECTIVE: Post-traumatic growth typically refers to enduring positive psychological change experienced as a result of adversity, trauma, or highly challenging life circumstances. Critics have challenged insights from much of the prior research on this topic, pinpointing its significant methodological limitations. In response to these critiques, we propose that post-traumatic growth can be more accurately captured in terms of personality change-an approach that affords a more rigorous examination of the phenomenon. METHOD: We outline a set of conceptual and methodological questions and considerations for future work on the topic of post-traumatic growth. RESULTS: We provide a series of recommendations for researchers from across the disciplines of clinical/counseling, developmental, health, personality, and social psychology and beyond, who are interested in improving the quality of research examining resilience and growth in the context of adversity. CONCLUSION: We are hopeful that these recommendations will pave the way for a more accurate understanding of the ubiquity, durability, and causal processes underlying post-traumatic growth.


Assuntos
Crescimento Psicológico Pós-Traumático , Transtornos de Estresse Pós-Traumáticos , Humanos , Personalidade , Transtornos da Personalidade
10.
J Pers ; 86(1): 83-96, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27716921

RESUMO

OBJECTIVE: Theory and research have emphasized the impact of life events on personality trait change. In this article, we review prospective research on personality trait change in response to nine major life events in the broader domains of love and work. METHOD: We expected to find that life events lead to personality trait change to the extent that they have a lasting influence on individuals' thoughts, feelings, and behavior. Moreover, we predicted that love-related life events such as marriage or parenthood would be more strongly related to changes in traits that emphasize affective content, whereas work-related life events would be more likely to lead to change in traits that reflect behavioral or cognitive content. RESULTS: The current state of research provided some evidence that life events can lead to changes in personality traits and that different life events may be differently related to specific trait domains. CONCLUSIONS: A more general conclusion emerging from this review is that the evidence for the nature, shape, and timing of personality trait change in response to life events is still preliminary. We discuss the implications of the results for theory and research and provide directions for future studies on life events and personality trait change.


Assuntos
Acontecimentos que Mudam a Vida , Personalidade , Teoria Psicológica , Humanos , Casamento/psicologia , Poder Familiar/psicologia , Aposentadoria/psicologia , Trabalho/psicologia
11.
Behav Brain Sci ; 41: e157, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-31064530

RESUMO

The commentaries on our target article are insightful and constructive. There were some critical notes, but many commentaries agreed with, or even amplified our message. The first section of our response addresses comments pertaining to specific parts of the target article. The second section provides a response to the commentaries' suggestions to make replication mainstream. The final section contains concluding remarks.


Assuntos
Ciências do Comportamento , Resolução de Problemas
12.
Behav Brain Sci ; 41: e120, 2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-29065933

RESUMO

Many philosophers of science and methodologists have argued that the ability to repeat studies and obtain similar results is an essential component of science. A finding is elevated from single observation to scientific evidence when the procedures that were used to obtain it can be reproduced and the finding itself can be replicated. Recent replication attempts show that some high profile results - most notably in psychology, but in many other disciplines as well - cannot be replicated consistently. These replication attempts have generated a considerable amount of controversy, and the issue of whether direct replications have value has, in particular, proven to be contentious. However, much of this discussion has occurred in published commentaries and social media outlets, resulting in a fragmented discourse. To address the need for an integrative summary, we review various types of replication studies and then discuss the most commonly voiced concerns about direct replication. We provide detailed responses to these concerns and consider different statistical ways to evaluate replications. We conclude there are no theoretical or statistical obstacles to making direct replication a routine aspect of psychological science.

13.
Glob Chang Biol ; 22(4): 1406-20, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26499288

RESUMO

We combined two existing datasets of vegetation aboveground biomass (AGB) (Proceedings of the National Academy of Sciences of the United States of America, 108, 2011, 9899; Nature Climate Change, 2, 2012, 182) into a pan-tropical AGB map at 1-km resolution using an independent reference dataset of field observations and locally calibrated high-resolution biomass maps, harmonized and upscaled to 14 477 1-km AGB estimates. Our data fusion approach uses bias removal and weighted linear averaging that incorporates and spatializes the biomass patterns indicated by the reference data. The method was applied independently in areas (strata) with homogeneous error patterns of the input (Saatchi and Baccini) maps, which were estimated from the reference data and additional covariates. Based on the fused map, we estimated AGB stock for the tropics (23.4 N-23.4 S) of 375 Pg dry mass, 9-18% lower than the Saatchi and Baccini estimates. The fused map also showed differing spatial patterns of AGB over large areas, with higher AGB density in the dense forest areas in the Congo basin, Eastern Amazon and South-East Asia, and lower values in Central America and in most dry vegetation areas of Africa than either of the input maps. The validation exercise, based on 2118 estimates from the reference dataset not used in the fusion process, showed that the fused map had a RMSE 15-21% lower than that of the input maps and, most importantly, nearly unbiased estimates (mean bias 5 Mg dry mass ha(-1) vs. 21 and 28 Mg ha(-1) for the input maps). The fusion method can be applied at any scale including the policy-relevant national level, where it can provide improved biomass estimates by integrating existing regional biomass maps as input maps and additional, country-specific reference datasets.


Assuntos
Biomassa , Mapas como Assunto , Conjuntos de Dados como Assunto , Modelos Teóricos , Árvores , Clima Tropical
14.
Ecol Appl ; 26(2): 545-56, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27209794

RESUMO

Human activities have exerted a powerful influence on the biogeochemical cycles of nitrogen (N) and carbon (C) and drive changes that can be a challenge to predict given the influence of multiple environmental stressors. This study focused on understanding how land management and climate change have together influenced terrestrial N storage and watershed inorganic N export across boreal and sub-arctic landscapes in northern Sweden. Using long-term discharge and nutrient concentration data that have been collected continuously for over three decades, we calculated the hydrologic inorganic N export from nine watersheds in this region. We found a consistent decline in inorganic N export from 1985 to 2011 over the entire region from both small and large watersheds, despite the absence of any long-term trend in river discharge during this period. The steepest declines in inorganic N export were observed during the growing season, consistent with the hypothesis that observed changes are biologically mediated and are not the result of changes in long-term hydrology. Concurrent with the decrease in inorganic N export, we report sustained increases in terrestrial N accumulation in forest biomass and soils across northern Sweden. Given the close communication of nutrient and energy stores between plants, soils, and waters, our results indicate a regional tightening of the N cycle in an already N-limited environment as a result of changes in forest management and climate-mediated growth increases. Our results are consistent with declining inorganic N efflux previously reported from small headwater streams in other ecosystems and shed new light on the mechanisms controlling these patterns by identifying corresponding shifts in the terrestrial N balance, which have been altered by a combination of management activities and climate change.


Assuntos
Florestas , Nitrogênio/química , Rios/química , Suécia , Fatores de Tempo , Movimentos da Água , Poluentes Químicos da Água/química
16.
Remote Sens Environ ; 175: 65-72, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-28148973

RESUMO

Focusing on a Mediterranean Natura 2000 site in Italy, the effectiveness of the cross correlation analysis (CCA) technique for quantifying change in the area of semi-natural grasslands at different spatial resolutions (grain) was evaluated. In a fine scale analysis (2 m), inputs to the CCA were a) a semi-natural grasslands layer extracted from an existing validated land cover/land use (LC/LU) map (1:5000, time T1) and b) a more recent single date very high resolution (VHR) WorldView-2 image (time T2), with T2 > T1. The changes identified through the CCA were compared against those detected by applying a traditional post-classification comparison (PCC) technique to the same reference T1 map and an updated T2 map obtained by a knowledge driven classification of four multi-seasonal Worldview-2 input images. Specific changes observed were those associated with agricultural intensification and fires. The study concluded that prior knowledge (spectral class signatures, awareness of local agricultural practices and pressures) was needed for the selection of the most appropriate image (in terms of seasonality) to be acquired at T2. CCA was also applied to the comparison of the existing T1 map with recent high resolution (HR) Landsat 8 OLS images. The areas of change detected at VHR and HR were broadly similar with larger error values in HR change images.

17.
New Phytol ; 202(2): 415-421, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24444123

RESUMO

Studies evaluating plant-soil biota interactions in both native and introduced plant ranges are rare, and thus far have lacked robust experimental designs to account for several potential confounding factors. Here, we investigated the effects of soil biota on growth of Pinus contorta, which has been introduced from Canada to Sweden. Using Swedish and Canadian soils, we conducted two glasshouse experiments. The first experiment utilized unsterilized soil from each country, with a full-factorial cross of soil origin, tree provenance, and fertilizer addition. The second experiment utilized gamma-irradiated sterile soil from each country, with a full-factorial cross of soil origin, soil biota inoculation treatments, tree provenance, and fertilizer addition. The first experiment showed higher seedling growth on Swedish soil relative to Canadian soil. The second experiment showed this effect was due to differences in soil biotic communities between the two countries, and occurred independently of all other experimental factors. Our results provide strong evidence that plant interactions with soil biota can shift from negative to positive following introduction to a new region, and are relevant for understanding the success of some exotic forest plantations, and invasive and range-expanding native species.


Assuntos
Espécies Introduzidas , Microbiota , Pinus/microbiologia , Plântula/microbiologia , Microbiologia do Solo , Solo , Canadá , Pinus/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Suécia , Árvores/crescimento & desenvolvimento , Árvores/microbiologia
18.
Qual Life Res ; 23(10): 2809-18, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24890827

RESUMO

PURPOSE: The present paper assessed the validity of single-item life satisfaction measures by comparing single-item measures to the Satisfaction with Life Scale (SWLS)-a more psychometrically established measure. METHODS: Two large samples from Washington (N = 13,064) and Oregon (N = 2,277) recruited by the Behavioral Risk Factor Surveillance System and a representative German sample (N = 1,312) recruited by the Germany Socio-Economic Panel were included in the present analyses. Single-item life satisfaction measures and the SWLS were correlated with theoretically relevant variables, such as demographics, subjective health, domain satisfaction, and affect. The correlations between the two life satisfaction measures and these variables were examined to assess the construct validity of single-item life satisfaction measures. RESULTS: Consistent across three samples, single-item life satisfaction measures demonstrated substantial degree of criterion validity with the SWLS (zero-order r = 0.62-0.64; disattenuated r = 0.78-0.80). Patterns of statistical significance for correlations with theoretically relevant variables were the same across single-item measures and the SWLS. Single-item measures did not produce systematically different correlations compared to the SWLS (average difference = 0.001-0.005). The average absolute difference in the magnitudes of the correlations produced by single-item measures and the SWLS was very small (average absolute difference = 0.015-0.042). CONCLUSIONS: Single-item life satisfaction measures performed very similarly compared to the multiple-item SWLS. Social scientists would get virtually identical answer to substantive questions regardless of which measure they use.


Assuntos
Satisfação Pessoal , Psicometria/métodos , Qualidade de Vida/psicologia , Inquéritos e Questionários , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade
19.
J Pers ; 82(5): 367-78, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24033325

RESUMO

The idea that strong social relationships can buffer the negative effects of stress on well-being has received much attention in existing literature. However, previous studies have used less than ideal research designs to test this hypothesis, making it difficult to draw firm conclusions regarding the buffering effects of social support. In this study, we examined the buffering hypothesis in the context of reaction and adaptation to widowhood in three large longitudinal datasets. We tested whether social relationships moderated reaction and adaptation to widowhood in samples of people who experienced loss of a spouse from three longitudinal datasets of nationally representative samples from Germany (N = 1,195), Great Britain (N = 562), and Australia (N = 298). We found no evidence that social relationships established before widowhood buffered either reaction or adaptation to the death of one's spouse. Similarly, social relationships that were in place during the first year of widowhood did not help widows and widowers recover from this difficult event. Social relationships acquired prior to widowhood, or those available in early stages of widowhood, do not appear to explain individual differences in adaptation to loss.


Assuntos
Adaptação Psicológica , Relações Interpessoais , Solidão/psicologia , Apoio Social , Viuvez/psicologia , Idoso , Austrália , Mecanismos de Defesa , Depressão/psicologia , Feminino , Alemanha , Pesar , Humanos , Acontecimentos que Mudam a Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reino Unido
20.
Cells ; 13(2)2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38247856

RESUMO

BACKGROUND: Azithromycin (AZM) is widely being used for treating patients with cystic fibrosis (pwCF) following clinical trials demonstrating improved lung function and fewer incidents of pulmonary exacerba-tions. While the precise mechanisms remain elusive, immunomodulatory actions are thought to be involved. We previously reported impaired phagocytosis and defective anti-inflammatory M2 macrophage polarization in CF. This study systematically analyzed the effect of AZM on the functions of unpolarized and M1/M2 polarized macrophages in CF. METHODS: Monocytes, isolated from the venous blood of patients with CF (pwCF) and healthy controls (HCs), were differentiated into monocyte-derived macrophages (MDMs) and subsequently infected with P. aeruginosa. P. aeruginosa uptake and killing by MDMs in the presence or absence of AZM was studied. M1 and M2 macrophage polarizations were induced and their functions and cytokine release were analyzed. RESULTS: Following AZM treatment, both HC and CF MDMs exhibited a significant increase in P. aeruginosa uptake and killing, however, lysosomal acidification remained unchanged. AZM treatment led to higher activation of ERK1/2 in both HC and CF MDMs. Pharmacological inhibition of ERK1/2 using U0126 significantly reduced P. aeruginosa uptake in HC MDMs. M1 macrophage polarization remained unaffected; however, AZM treatment led to increased IL-6 and IL-10 release in both HC and CF M1 macrophages. AZM also significantly increased the phagocytic index for both pHrodo E. coli and S. aureus in CF M1 macrophages. In CF, AZM treatment promoted anti-inflammatory M2 macrophage polarization, with an increased percentage of CD209+ M2 macrophages, induction of the M2 gene CCL18, along with its secretion in the culture supernatant. However, AZM d'd not restore endocytosis in CF, another essential feature of M2 macrophages. CONCLUSIONS: This study highlights the cellular functions and molecular targets of AZM which may involve an improved uptake of both Gram-positive and Gram-negative bacteria, restored anti-inflammatory macrophage polarization in CF. This may in turn shape the reduced lung inflammation observed in clinical trials. In addition, we confirmed the role of ERK1/2 activation for bacterial uptake.


Assuntos
Azitromicina , Fibrose Cística , Humanos , Azitromicina/farmacologia , Bactérias Gram-Negativas , Antibacterianos/farmacologia , Fibrose Cística/tratamento farmacológico , Escherichia coli , Staphylococcus aureus , Bactérias Gram-Positivas , Macrófagos , Anti-Inflamatórios/farmacologia
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