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1.
Nature ; 608(7923): 528-533, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35585230

RESUMO

Evidence exists that tree mortality is accelerating in some regions of the tropics1,2, with profound consequences for the future of the tropical carbon sink and the global anthropogenic carbon budget left to limit peak global warming below 2 °C. However, the mechanisms that may be driving such mortality changes and whether particular species are especially vulnerable remain unclear3-8. Here we analyse a 49-year record of tree dynamics from 24 old-growth forest plots encompassing a broad climatic gradient across the Australian moist tropics and find that annual tree mortality risk has, on average, doubled across all plots and species over the last 35 years, indicating a potential halving in life expectancy and carbon residence time. Associated losses in biomass were not offset by gains from growth and recruitment. Plots in less moist local climates presented higher average mortality risk, but local mean climate did not predict the pace of temporal increase in mortality risk. Species varied in the trajectories of their mortality risk, with the highest average risk found nearer to the upper end of the atmospheric vapour pressure deficit niches of species. A long-term increase in vapour pressure deficit was evident across the region, suggesting that thresholds involving atmospheric water stress, driven by global warming, may be a primary cause of increasing tree mortality in moist tropical forests.


Assuntos
Atmosfera , Estresse Fisiológico , Árvores , Clima Tropical , Água , Aclimatação , Atmosfera/química , Austrália , Biomassa , Carbono/metabolismo , Sequestro de Carbono , Desidratação , Aquecimento Global/estatística & dados numéricos , História do Século XX , História do Século XXI , Umidade , Densidade Demográfica , Risco , Fatores de Tempo , Árvores/classificação , Árvores/crescimento & desenvolvimento , Árvores/metabolismo , Água/análise , Água/metabolismo
2.
Ecol Lett ; 27(6): e14449, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38857318

RESUMO

When plants die, neighbours escape competition. Living conspecifics could disproportionately benefit because they are freed from negative intraspecific processes; however, if the negative effects of past conspecific neighbours persist, other species might be advantaged, and diversity might be maintained through legacy effects. We examined legacy effects in a mapped forest by modelling the survival of 37,212 trees of 23 species using four neighbourhood properties: living conspecific, living heterospecific, legacy conspecific (dead conspecifics) and legacy heterospecific densities. Legacy conspecific effects proved nearly four times stronger than living conspecific effects; changes in annual survival associated with legacy conspecific density were 1.5% greater than living conspecific effects. Over 90% of species were negatively impacted by legacy conspecific density, compared to 47% by living conspecific density. Our results emphasize that legacies of trees alter community dynamics, revealing that prior research may have underestimated the strength of density dependent interactions by not considering legacy effects.


Assuntos
Florestas , Densidade Demográfica , Árvores , Árvores/fisiologia , Dinâmica Populacional , Modelos Biológicos , Biodiversidade
3.
Glob Chang Biol ; 30(5): e17317, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747199

RESUMO

Each year, an average of 45 tropical cyclones affect coastal areas and potentially impact forests. The proportion of the most intense cyclones has increased over the past four decades and is predicted to continue to do so. Yet, it remains uncertain how topographical exposure and tree characteristics can mediate the damage caused by increasing wind speed. Here, we compiled empirical data on the damage caused by 11 cyclones occurring over the past 40 years, from 74 forest plots representing tropical regions worldwide, encompassing field data for 22,176 trees and 815 species. We reconstructed the wind structure of those tropical cyclones to estimate the maximum sustained wind speed (MSW) and wind direction at the studied plots. Then, we used a causal inference framework combined with Bayesian generalised linear mixed models to understand and quantify the causal effects of MSW, topographical exposure to wind (EXP), tree size (DBH) and species wood density (ρ) on the proportion of damaged trees at the community level, and on the probability of snapping or uprooting at the tree level. The probability of snapping or uprooting at the tree level and, hence, the proportion of damaged trees at the community level, increased with increasing MSW, and with increasing EXP accentuating the damaging effects of cyclones, in particular at higher wind speeds. Higher ρ decreased the probability of snapping and to a lesser extent of uprooting. Larger trees tended to have lower probabilities of snapping but increased probabilities of uprooting. Importantly, the effect of ρ decreasing the probabilities of snapping was more marked for smaller than larger trees and was further accentuated at higher MSW. Our work emphasises how local topography, tree size and species wood density together mediate cyclone damage to tropical forests, facilitating better predictions of the impacts of such disturbances in an increasingly windier world.


Assuntos
Tempestades Ciclônicas , Florestas , Árvores , Clima Tropical , Vento , Árvores/crescimento & desenvolvimento , Teorema de Bayes
4.
J Biol Chem ; 298(9): 102284, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35868561

RESUMO

cGMP-dependent protein kinase (PKG) represents a compelling drug target for treatment of cardiovascular diseases. PKG1 is the major effector of beneficial cGMP signaling which is involved in smooth muscle relaxation and vascular tone, inhibition of platelet aggregation and signaling that leads to cardioprotection. In this study, a novel piperidine series of activators previously identified from an ultrahigh-throughput screen were validated to directly bind partially activated PKG1α and subsequently enhance its kinase activity in a concentration-dependent manner. Compounds from initial optimization efforts showed an ability to activate PKG1α independent of the endogenous activator, cGMP. We demonstrate these small molecule activators mimic the effect of cGMP on the kinetic parameters of PKG1α by positively modulating the KM of the peptide substrate and negatively modulating the apparent KM for ATP with increase in catalytic efficiency, kcat. In addition, these compounds also allosterically modulate the binding affinity of cGMP for PKG1α by increasing the affinity of cGMP for the high-affinity binding site (CNB-A) and decreasing the affinity of cGMP for the low-affinity binding site (CNB-B). We show the mode of action of these activators involves binding to an allosteric site within the regulatory domain, near the CNB-B binding site. To the best of our knowledge, these are the first reported non-cGMP mimetic small molecules shown to directly activate PKG1α. Insights into the mechanism of action of these compounds will enable future development of cardioprotective compounds that function through novel modes of action for the treatment of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Proteína Quinase Dependente de GMP Cíclico Tipo I , GMP Cíclico , Piperidinas , Trifosfato de Adenosina/metabolismo , Regulação Alostérica/efeitos dos fármacos , Sítio Alostérico/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/enzimologia , GMP Cíclico/metabolismo , Proteína Quinase Dependente de GMP Cíclico Tipo I/metabolismo , Humanos , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
5.
Environ Monit Assess ; 195(4): 514, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36973586

RESUMO

The underexplored intertidal ecosystems of Antarctica are facing rapid changes in important environmental factors. Associated with temperature increase, reduction in coastal ice will soon expose new ice-free areas that will be colonized by local or distant biota. To enable detection of future changes in faunal composition, a biodiversity baseline is urgently required. Here, we evaluated intertidal faunal diversity at 13 locations around the Gerlache Strait (western Antarctic Peninsula), using a combination of a quadrat approach, morphological identification and genetic characterization. Our data highlight a community structure comprising four generally distributed and highly abundant species (the flatworm Obrimoposthia wandeli, the bivalve Kidderia subquadrata, and the gastropods Laevilitorina umbilicata and Laevilitorina caliginosa) as well as 79 rarer and less widely encountered species. The most abundant species thrive in the intertidal zone due to their ability to either survive overwinter in situ or to rapidly colonize this zone when conditions allow. In addition, we confirmed the presence of multiple trophic levels at nearly all locations, suggesting that complex inter-specific interactions occur within these communities. Diversity indices contrasted between sampling locations (from 3 to 32 species) and multivariate approaches identified three main groups. This confirms the importance of environmental heterogeneity in shaping diversity patterns within the investigated area. Finally, we provide the first genetic and photographic baseline of the Antarctic intertidal fauna (106 sequences, 137 macrophotographs), as well as preliminary insights on the biogeography of several species. Taken together, these results provide a timely catalyst to assess the diversity and to inform studies of the potential resilience of these intertidal communities.


Assuntos
Bivalves , Ecossistema , Animais , Regiões Antárticas , Monitoramento Ambiental , Biodiversidade
6.
Glob Chang Biol ; 28(4): 1414-1432, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34741793

RESUMO

A better understanding of how climate affects growth in tree species is essential for improved predictions of forest dynamics under climate change. Long-term climate averages (mean climate) drive spatial variations in species' baseline growth rates, whereas deviations from these averages over time (anomalies) can create growth variation around the local baseline. However, the rarity of long-term tree census data spanning climatic gradients has so far limited our understanding of their respective role, especially in tropical systems. Furthermore, tree growth sensitivity to climate is likely to vary widely among species, and the ecological strategies underlying these differences remain poorly understood. Here, we utilize an exceptional dataset of 49 years of growth data for 509 tree species across 23 tropical rainforest plots along a climatic gradient to examine how multiannual tree growth responds to both climate means and anomalies, and how species' functional traits mediate these growth responses to climate. We show that anomalous increases in atmospheric evaporative demand and solar radiation consistently reduced tree growth. Drier forests and fast-growing species were more sensitive to water stress anomalies. In addition, species traits related to water use and photosynthesis partly explained differences in growth sensitivity to both climate means and anomalies. Our study demonstrates that both climate means and anomalies shape tree growth in tropical forests and that species traits can provide insights into understanding these demographic responses to climate change, offering a promising way forward to forecast tropical forest dynamics under different climate trajectories.


Assuntos
Árvores , Clima Tropical , Mudança Climática , Florestas , Folhas de Planta
7.
New Phytol ; 232(2): 579-594, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34292602

RESUMO

Positive biodiversity-ecosystem function relationships (BEFRs) have been widely documented, but it is unclear if BEFRs should be expected in disturbance-driven systems. Disturbance may limit competition and niche differentiation, which are frequently posited to underlie BEFRs. We provide the first exploration of the relationship between tree species diversity and biomass, one measure of ecosystem function, across southern African woodlands and savannas, an ecological system rife with disturbance from fire, herbivores and humans. We used > 1000 vegetation plots distributed across 10 southern African countries and structural equation modelling to determine the relationship between tree species diversity and above-ground woody biomass, accounting for interacting effects of resource availability, disturbance by fire, tree stem density and vegetation type. We found positive effects of tree species diversity on above-ground biomass, operating via increased structural diversity. The observed BEFR was highly dependent on organismal density, with a minimum threshold of c. 180 mature stems ha-1 . We found that water availability mainly affects biomass indirectly, via increasing species diversity. The study underlines the close association between tree diversity, ecosystem structure, environment and function in highly disturbed savannas and woodlands. We suggest that tree diversity is an under-appreciated determinant of wooded ecosystem structure and function.


Assuntos
Ecossistema , Árvores , Biodiversidade , Florestas , Pradaria
8.
Heredity (Edinb) ; 127(6): 522-534, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34743188

RESUMO

Understanding the spatial structure of genetic diversity provides insights into a populations' genetic status and enables assessment of its capacity to counteract the effects of genetic drift. Such knowledge is particularly scarce for the snow leopard, a conservation flagship species of Central Asia mountains. Focusing on a snow leopard population in the Qilian mountains of Gansu Province, China, we characterised the spatial genetic patterns by incorporating spatially explicit indices of diversity and multivariate analyses, based on different inertia levels of Principal Component Analysis (PCA). We compared two datasets differing in the number of loci and individuals. We found that genetic patterns were significantly spatially structured and were characterised by a broad geographical division coupled with a fine-scale cline of differentiation. Genetic admixture was detected in two adjoining core areas characterised by higher effective population size and allelic diversity, compared to peripheral localities. The power to detect significant spatial relationships depended primarily on the number of loci, and secondarily on the number of PCA axes. Spatial patterns and indices of diversity highlighted the cryptic structure of snow leopard genetic diversity, likely driven by its ability to disperse over large distances. In combination, the species' low allelic richness and large dispersal ability result in weak genetic differentiation related to major geographical features and isolation by distance. This study illustrates how cryptic genetic patterns can be investigated and analysed at a fine spatial scale, providing insights into the spatially variable isolation effects of both geographic distance and landscape resistance.


Assuntos
Panthera , Animais , China , Variação Genética , Genética Populacional , Geografia , Humanos , Repetições de Microssatélites , Panthera/genética , Densidade Demográfica
9.
Ecology ; 99(10): 2159-2166, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30039615

RESUMO

Eigenvector-mapping methods such as Moran's eigenvector maps (MEM) are derived from a spatial weighting matrix (SWM) that describes the relations among a set of sampled sites. The specification of the SWM is a crucial step, but the SWM is generally chosen arbitrarily, regardless of the sampling design characteristics. Here, we compare the statistical performances of different types of SWMs (distance-based or graph-based) in contrasted realistic simulation scenarios. Then, we present an optimization method and evaluate its performances compared to the arbitrary choice of the most-widely used distance-based SWM. Results showed that the distance-based SWMs generally had lower power and accuracy than other specifications, and strongly underestimated spatial signals. The optimization method, using a correction procedure for multiple tests, had a correct type I error rate, and had higher power and accuracy than an arbitrary choice of the SWM. Nevertheless, the power decreased when too many SWMs were compared, resulting in a trade-off between the gain of accuracy and the loss of power. We advocate that future studies should optimize the choice of the SWM using a small set of appropriate candidates. R functions to implement the optimization are available in the adespatial package and are detailed in a tutorial.


Assuntos
Ecologia , Modelos Teóricos , Software
10.
J Exp Biol ; 221(Pt 6)2018 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-29444845

RESUMO

Bacteria can damage sperm and thus reduce the reproductive success of both males and females; selection should therefore favour the evolution of antimicrobial protection. Eusocial hymenopterans might be particularly affected by such bacterial infections because of their mating ecology. In both sexes, mating is restricted to a short window early in the adult stage; there are no further chances to mate later in life. Males die shortly after mating, but queens use the acquired sperm to fertilise their eggs for years, sometimes decades. The reproductive success of both sexes is, thus, ultimately sperm-limited, which maintains strong selection for high sperm viability before and after storage. We tested the antibacterial activity of the contents of the male and female sperm-storage organs - the accessory testes and the spermatheca, respectively. As our study species, we used the bacterium Escherichia coli and the garden ant Lasius niger, whose queens can live for several decades. Our results provide the first empirical evidence that male and female sperm-storage organs display different antibacterial activity. While the contents of the accessory testes actually enhanced bacterial growth, the contents of the spermatheca strongly inhibited it. Furthermore, mating appears to activate the general immune system in queens. However, antimicrobial activity in both the spermatheca and the control tissue (head-thorax homogenate) declined rapidly post-mating, consistent with a trade-off between immunity and reproduction. Overall, this study suggests that ejaculates undergo an immune 'flush' at the time of mating, allowing storage of sperm cells free of bacteria.


Assuntos
Antibacterianos/metabolismo , Formigas/fisiologia , Espermatozoides/fisiologia , Animais , Antibacterianos/isolamento & purificação , Feminino , Masculino
11.
J Clin Psychol Med Settings ; 25(2): 127-156, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28975500

RESUMO

The Primary Care Behavioral Health (PCBH) model of service delivery is being used increasingly as an effective way to integrate behavioral health services into primary care. Despite its growing popularity, scientifically robust research on the model is lacking. In this article, we provide a qualitative review of published PCBH model research on patient and implementation outcomes. We review common barriers and potential solutions for improving the quantity and quality of PCBH model research, the vital data that need to be collected over the next 10 years, and how to collect those data.


Assuntos
Medicina do Comportamento/organização & administração , Prestação Integrada de Cuidados de Saúde/organização & administração , Pesquisa sobre Serviços de Saúde/organização & administração , Atenção Primária à Saúde/organização & administração , Medicina do Comportamento/tendências , Prestação Integrada de Cuidados de Saúde/tendências , Previsões , Necessidades e Demandas de Serviços de Saúde/organização & administração , Necessidades e Demandas de Serviços de Saúde/tendências , Pesquisa sobre Serviços de Saúde/tendências , Humanos , Comunicação Interdisciplinar , Colaboração Intersetorial , Equipe de Assistência ao Paciente/organização & administração , Equipe de Assistência ao Paciente/tendências , Atenção Primária à Saúde/tendências , Estados Unidos
12.
Med Educ Online ; 29(1): 2295049, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38320114

RESUMO

Patient interviewing pedagogy in medical education has not evolved to comprehensively capture the biopsychosocial model of healthcare delivery. While gathering a patient's social history targets important aspects of social context it does not adequately capture and account for the real-time reassessment required to understand evolving factors that influence exposure to drivers of health inequities, social determinants of health, and access to supports that promote health. The authors offer a patient interviewing approach called the Contextual Interview (CI) that specifically targets dynamic and ever-changing social context information. To substantiate the use of the CI in medical education, the authors conducted a qualitative review of the Accreditation Council for Graduate Medical Education Milestones for primary care specialties (Family Medicine, Internal Medicine, and Pediatrics). Milestones were coded to the extent to which they reflected the learner's need to acknowledge, assess, synthesize and/or apply patient contextual data in real-time patient encounters. Approximately 1 in 5 milestones met the context-related and patient-facing criteria. This milestone review further highlights the need for more intentional training in eliciting meaningful social context data during patient interviewing. The CI as a cross-cutting, practical, time-conscious, and semi-structured patient interviewing approach that deliberately elicits information to improve the clinician's sense and understanding of a patient's social context. The authors reviewed future directions in researching adapted versions of the CI for undergraduate and graduate medical education.


Assuntos
Promoção da Saúde , Internato e Residência , Humanos , Criança , Educação de Pós-Graduação em Medicina , Medicina Interna/educação , Meio Social , Atenção à Saúde , Competência Clínica
13.
Bioorg Med Chem Lett ; 23(12): 3650-3, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23659858

RESUMO

In an effort to understand the origin of blood-pressure lowering effects observed in recent clinical trials with 11ß-HSD1 inhibitors, we examined a set of 11ß-HSD1 inhibitors in a series of relevant in vitro and in vivo assays. Select 11ß-HSD1 inhibitors reduced blood pressure in our preclinical models but most or all of the blood pressure lowering may be mediated by a 11ß-HSD1 independent pathway.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/enzimologia , Triazóis/farmacologia , Animais , Humanos , Camundongos , Camundongos Knockout , Ratos , Ratos Endogâmicos SHR
14.
Psychol Serv ; 20(2): 335-342, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35737544

RESUMO

Community-based primary care settings play an important role in the provision of health care to vulnerable populations, as well as in primary care education. Much attention has been given to medical education in community-based primary care and as the need for workforce development grows for behavioral health in primary care, clinical supervision of prelicensure psychology learners in primary care will also need greater attention. Clinical supervision not only impacts learner professional development but also impacts the patient care learners provide. The purpose of this article is to give attention to clinical supervision within the primary care behavioral health (PCBH) model in the context of community-based primary care. The intersection of supervision approaches in specialty mental health care and medical education will be presented, as well as how these approaches can be combined when working with learners within PCBH. Additionally, challenges to clinical supervision in primary care will be discussed as well as solutions to improve not only workforce development in PCBH but also professional development for clinical supervisors in primary care. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Medicina do Comportamento , Atenção Primária à Saúde , Humanos , Preceptoria , Medicina do Comportamento/educação , Atenção à Saúde , Desenvolvimento de Pessoal
15.
JCI Insight ; 8(1)2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36454644

RESUMO

Podocyte injury and loss are key drivers of primary and secondary glomerular diseases, such as focal segmental glomerulosclerosis (FSGS) and diabetic kidney disease (DKD). We previously demonstrated the renoprotective role of protein S (PS) and its cognate tyrosine-protein kinase receptor, TYRO3, in models of FSGS and DKD and that their signaling exerts antiapoptotic and antiinflammatory effects to confer protection against podocyte loss. Among the 3 TAM receptors (TYRO3, AXL, and MER), only TYRO3 expression is largely restricted to podocytes, and glomerular TYRO3 mRNA expression negatively correlates with human glomerular disease progression. Therefore, we posited that the agonistic PS/TYRO3 signaling could serve as a potential therapeutic approach to attenuate glomerular disease progression. As PS function is not limited to TYRO3-mediated signal transduction but includes its anticoagulant activity, we focused on the development of TYRO3 agonists as an optimal therapeutic approach to glomerular disease. Among the small-molecule TYRO3 agonistic compounds screened, compound 10 (C-10) showed a selective activation of TYRO3 without any effects on AXL or MER. We also confirmed that C-10 directly binds to TYRO3, but not the other receptors. In vivo, C-10 attenuated proteinuria, glomerular injury, and podocyte loss in mouse models of Adriamycin-induced nephropathy and a db/db model of type 2 diabetes. Moreover, these renoprotective effects of C-10 were lost in Tyro3-knockout mice, indicating that C-10 is a selective agonist of TYRO3 activity that mitigates podocyte injury and glomerular disease. Therefore, C-10, a TYRO3 agonist, could be potentially developed as a new therapy for glomerular disease.


Assuntos
Diabetes Mellitus Tipo 2 , Glomerulosclerose Segmentar e Focal , Podócitos , Camundongos , Animais , Humanos , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Glomérulos Renais/metabolismo , Podócitos/metabolismo , Camundongos Knockout , Proteínas de Transporte/metabolismo , Progressão da Doença , Receptores Proteína Tirosina Quinases/metabolismo
16.
Ecology ; 104(7): e4053, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37079023

RESUMO

Understanding how biotic interactions and environmental filtering mediated by soil properties shape plant community assembly is a major challenge in ecology, especially when studying complex and hyperdiverse ecosystems like tropical forests. To shed light on the influence of both factors, we examined how the edaphic optimum of species (their niche position) related to their edaphic range (their niche breadth) along different environmental gradients and how this translates into functional strategies. Here we tested four scenarios describing the shape of the niche breadth-niche position relationship, including one neutral scenario and three scenarios proposing different relative influences of abiotic and biotic factors on community assembly along a soil resource gradient. To do so, we used soil concentration data for five key nutrients (N, P, Ca, Mg, and K), along with accurate measurements of 14 leaf, stem, and root traits for 246 tree species inventoried in 101 plots located across Eastern (French Guiana) and Western (Peru) Amazonia. We found that species niche breadth increased linearly with species niche position along each soil nutrient gradient. This increase was associated with more resource acquisitive traits in the leaves and the roots for soil N, Ca, Mg, and K concentration, while it was negatively associated with wood density for soil P concentration. These observations agreed with one of our hypothetical scenarios in which species with resource conservation traits are confined to the most nutrient-depleted soils (abiotic filter), but they are outperformed by faster-growing species in more fertile conditions (biotic filter). Our results refine and strengthen support for niche theories of species assembly while providing an integrated approach to improving forest management policies.


Assuntos
Ecossistema , Árvores , Florestas , Madeira , Solo , Clima Tropical
17.
Proc Natl Acad Sci U S A ; 106(39): 16764-9, 2009 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-19805370

RESUMO

25-Hydroxycholesterol is produced in mammalian tissues. The function of this oxysterol is unknown. Here we describe a central role for 25-hydroxycholesterol in regulating the immune system. In initial experiments, we found that stimulation of macrophage Toll-like receptors (TLR) induced expression of cholesterol 25-hydroxylase and the synthesis of 25-hydroxycholesterol. Treatment of naïve B cells with nanomolar concentrations of 25-hydroxycholesterol suppressed IL-2-mediated stimulation of B cell proliferation, repressed activation-induced cytidine deaminase (AID) expression, and blocked class switch recombination, leading to markedly decreased IgA production. Consistent with these findings, deletion of the mouse cholesterol 25-hydroxylase gene caused an increase in serum IgA. Conversely, inactivation of the CYP7B1 oxysterol 7alpha-hydroxylase, which degrades 25-hydroxycholesterol, decreased serum IgA. The suppression of IgA class switching in B cells by a macrophage-derived sterol in response to TLR activation provides a mechanism for local and systemic negative regulation of the adaptive immune response by the innate immune system.


Assuntos
Hidroxicolesteróis/metabolismo , Imunoglobulina A/biossíntese , Macrófagos/metabolismo , Receptores Toll-Like/metabolismo , Animais , Linfócitos B/metabolismo , Citocinas/metabolismo , Camundongos , Camundongos Transgênicos , Esteroide Hidroxilases/genética , Esteroide Hidroxilases/metabolismo
18.
Fam Syst Health ; 40(2): 283-285, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35666898

RESUMO

Comments on the original article by Wolk et al. (see record 2022-18591-001) regarding the implementation of evidence-based practices in non-specialty mental health settings. The authors both had tremendous gratitude for Wolk et al.'s (2022) ability to accurately describe and elucidate numerous difficulties that frontline workers experience, especially in nonspecialty mental health (SMH) settings, such as primary care where we work. With increased identification of implementation barriers, those working in non-SMH settings can mitigate these challenges via intentional strategizing upfront, considering settings' contexts (as suggested by Wolk et al.), and normalizing the need for ongoing troubleshooting. The authors appreciated the elucidation that the majority of those receiving support for mental health receive care in non-SMH settings. As much as it is imperative for those working in non-SMH settings to learn concepts illuminated from the mental health field via evidence-based (EB) practices, when it comes to reaching the masses and implementation strategies, the field might have much to learn from these non-SMH settings. When it comes to integration of siloed fields, all can benefit. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Serviços de Saúde Mental , Saúde Mental , Prática Clínica Baseada em Evidências , Humanos
19.
Nat Ecol Evol ; 6(7): 878-889, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35577983

RESUMO

Tropical forests are some of the most biodiverse ecosystems in the world, yet their functioning is threatened by anthropogenic disturbances and climate change. Global actions to conserve tropical forests could be enhanced by having local knowledge on the forests' functional diversity and functional redundancy as proxies for their capacity to respond to global environmental change. Here we create estimates of plant functional diversity and redundancy across the tropics by combining a dataset of 16 morphological, chemical and photosynthetic plant traits sampled from 2,461 individual trees from 74 sites distributed across four continents together with local climate data for the past half century. Our findings suggest a strong link between climate and functional diversity and redundancy with the three trait groups responding similarly across the tropics and climate gradient. We show that drier tropical forests are overall less functionally diverse than wetter forests and that functional redundancy declines with increasing soil water and vapour pressure deficits. Areas with high functional diversity and high functional redundancy tend to better maintain ecosystem functioning, such as aboveground biomass, after extreme weather events. Our predictions suggest that the lower functional diversity and lower functional redundancy of drier tropical forests, in comparison with wetter forests, may leave them more at risk of shifting towards alternative states in face of further declines in water availability across tropical regions.


Assuntos
Mudança Climática , Ecossistema , Florestas , Árvores , Água
20.
Biochim Biophys Acta ; 1801(11): 1221-31, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20673851

RESUMO

Cerebral 3α-hydroxysteroid dehydrogenase (3α-HSD) activity was suggested to be responsible for the local directed formation of neuroactive 5α,3α-tetrahydrosteroids (5α,3α-THSs) from 5α-dihydrosteroids. We show for the first time that within human brain tissue 5α-dihydroprogesterone and 5α-dihydrotestosterone are converted via non-stereo-selective 3-ketosteroid reductase activity to produce the respective 5α,3α-THSs and 5α,3ß-THSs. Apart from this, we prove that within the human temporal lobe and limbic system cytochrome P450c17 and 3ß-HSD/Δ(5-4) ketosteroid isomerase are not expressed. Thus, it appears that these brain regions are unable to conduct de novo biosynthesis of Δ(4)-3-ketosteroids from Δ(5)-3ß-hydroxysteroids. Consequently, the local formation of THSs will depend on the uptake of circulating Δ(4)-3-ketosteroids such as progesterone and testosterone. 3α- and 3ß-HSD activity were (i) equally enriched in the cytosol, (ii) showed equal distribution between cerebral neocortex and subcortical white matter without sex- or age-dependency, (iii) demonstrated a strong and significant positive correlation when comparing 46 different specimens and (iv) exhibited similar sensitivities to different inhibitors of enzyme activity. These findings led to the assumption that cerebral 3-ketosteroid reductase activity might be catalyzed by a single enzyme and is possibly attributed to the expression of a soluble AKR1C aldo-keto reductase. AKR1Cs are known to act as non-stereo-selective 3-ketosteroid reductases; low AKR1C mRNA expression was detected. However, the cerebral 3-ketosteroid reductase was clearly refractory to inhibition by AKR1C inhibitors indicating the expression of a currently unidentified enzyme. Its lack of stereo-selectivity is of physiological significance, since only 5α,3α-THSs enhance the effect of GABA on the GABA(A) receptor, whereas 5α,3ß-THSs are antagonists.


Assuntos
20-Hidroxiesteroide Desidrogenases/genética , Encéfalo/metabolismo , Regulação Enzimológica da Expressão Gênica , 20-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , 3-Hidroxiesteroide Desidrogenases/metabolismo , Adulto , Idoso , Encéfalo/patologia , Linhagem Celular Tumoral , Cromatografia em Camada Fina/métodos , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Lactente , Pessoa de Meia-Idade , Esteroide 17-alfa-Hidroxilase/genética , Esteroides/química , Lobo Temporal/patologia
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