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1.
Am J Hum Genet ; 110(11): 1919-1937, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37827158

RESUMO

Misregulation of histone lysine methylation is associated with several human cancers and with human developmental disorders. DOT1L is an evolutionarily conserved gene encoding a lysine methyltransferase (KMT) that methylates histone 3 lysine-79 (H3K79) and was not previously associated with a Mendelian disease in OMIM. We have identified nine unrelated individuals with seven different de novo heterozygous missense variants in DOT1L through the Undiagnosed Disease Network (UDN), the SickKids Complex Care genomics project, and GeneMatcher. All probands had some degree of global developmental delay/intellectual disability, and most had one or more major congenital anomalies. To assess the pathogenicity of the DOT1L variants, functional studies were performed in Drosophila and human cells. The fruit fly DOT1L ortholog, grappa, is expressed in most cells including neurons in the central nervous system. The identified DOT1L variants behave as gain-of-function alleles in flies and lead to increased H3K79 methylation levels in flies and human cells. Our results show that human DOT1L and fly grappa are required for proper development and that de novo heterozygous variants in DOT1L are associated with a Mendelian disease.


Assuntos
Anormalidades Congênitas , Deficiências do Desenvolvimento , Histona-Lisina N-Metiltransferase , Humanos , Mutação com Ganho de Função , Histona-Lisina N-Metiltransferase/genética , Histonas/genética , Histonas/metabolismo , Lisina , Metilação , Metiltransferases/genética , Neoplasias/genética , Drosophila/genética , Proteínas de Drosophila/genética , Deficiências do Desenvolvimento/genética , Anormalidades Congênitas/genética
2.
Proc Natl Acad Sci U S A ; 120(15): e2201954120, 2023 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-37011220

RESUMO

Wildfire modifies the short- and long-term exchange of carbon between terrestrial ecosystems and the atmosphere, with impacts on ecosystem services such as carbon uptake. Dry western US forests historically experienced low-intensity, frequent fires, with patches across the landscape occupying different points in the fire-recovery trajectory. Contemporary perturbations, such as recent severe fires in California, could shift the historic stand-age distribution and impact the legacy of carbon uptake on the landscape. Here, we combine flux measurements of gross primary production (GPP) and chronosequence analysis using satellite remote sensing to investigate how the last century of fires in California impacted the dynamics of ecosystem carbon uptake on the fire-affected landscape. A GPP recovery trajectory curve of more than five thousand fires in forest ecosystems since 1919 indicated that fire reduced GPP by [Formula: see text] g C m[Formula: see text] y[Formula: see text]([Formula: see text]) in the first year after fire, with average recovery to prefire conditions after [Formula: see text] y. The largest fires in forested ecosystems reduced GPP by [Formula: see text] g C m[Formula: see text] y[Formula: see text] (n = 401) and took more than two decades to recover. Recent increases in fire severity and recovery time have led to nearly [Formula: see text] MMT CO[Formula: see text] (3-y rolling mean) in cumulative forgone carbon uptake due to the legacy of fires on the landscape, complicating the challenge of maintaining California's natural and working lands as a net carbon sink. Understanding these changes is paramount to weighing the costs and benefits associated with fuels management and ecosystem management for climate change mitigation.


Assuntos
Incêndios , Incêndios Florestais , Ecossistema , Florestas , California , Carbono
3.
Proc Natl Acad Sci U S A ; 120(19): e2221440120, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-37126706

RESUMO

Geraniol derived from essential oils of various plant species is widely used in the cosmetic and perfume industries. It is also an essential trait of the pleasant smell of rose flowers. In contrast to other monoterpenes which are produced in plastids via the methyl erythritol phosphate pathway, geraniol biosynthesis in roses relies on cytosolic NUDX1 hydrolase which dephosphorylates geranyl diphosphate (GPP). However, the metabolic origin of cytosolic GPP remains unknown. By feeding Rosa chinensis "Old Blush" flowers with pathway-specific precursors and inhibitors, combined with metabolic profiling and functional characterization of enzymes in vitro and in planta, we show that geraniol is synthesized through the cytosolic mevalonate (MVA) pathway by a bifunctional geranyl/farnesyl diphosphate synthase, RcG/FPPS1, producing both GPP and farnesyl diphosphate (FPP). The downregulation and overexpression of RcG/FPPS1 in rose petals affected not only geraniol and germacrene D emissions but also dihydro-ß-ionol, the latter due to metabolic cross talk of RcG/FPPS1-dependent isoprenoid intermediates trafficking from the cytosol to plastids. Phylogenetic analysis together with functional characterization of G/FPPS orthologs revealed that the G/FPPS activity is conserved among Rosaceae species. Site-directed mutagenesis and molecular dynamic simulations enabled to identify two conserved amino acids that evolved from ancestral FPPSs and contribute to GPP/FPP product specificity. Overall, this study elucidates the origin of the cytosolic GPP for NUDX1-dependent geraniol production, provides insights into the emergence of the RcG/FPPS1 GPPS activity from the ancestral FPPSs, and shows that RcG/FPPS1 plays a key role in the biosynthesis of volatile terpenoid compounds in rose flowers.


Assuntos
Geraniltranstransferase , Rosa , Geraniltranstransferase/genética , Ácido Mevalônico/metabolismo , Rosa/metabolismo , Citosol/metabolismo , Filogenia , Terpenos/metabolismo , Flores/metabolismo
4.
Proc Natl Acad Sci U S A ; 119(10): e2115627119, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35238668

RESUMO

SignificanceThe magnitude of the CO2 fertilization effect on terrestrial photosynthesis is uncertain because it is not directly observed and is subject to confounding effects of climatic variability. We apply three well-established eco-evolutionary optimality theories of gas exchange and photosynthesis, constraining the main processes of CO2 fertilization using measurable variables. Using this framework, we provide robust observationally inferred evidence that a strong CO2 fertilization effect is detectable in globally distributed eddy covariance networks. Applying our method to upscale photosynthesis globally, we find that the magnitude of the CO2 fertilization effect is comparable to its in situ counterpart but highlight the potential for substantial underestimation of this effect in tropical forests for many reflectance-based satellite photosynthesis products.

5.
Exp Dermatol ; 33(1): e14934, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37726967

RESUMO

Deficiency of the interleukin-36 receptor antagonist (DITRA) is a rare autoinflammatory disorder caused by mutations in the IL36RN gene. This mutation leads to a lack of functional interleukin-36 receptor antagonists (IL-36Ra), which results in an overactive immune system and chronic inflammation. Despite its rarity, numerous case series and individual reports in the literature emphasize the importance of recognizing and managing DITRA. Early identification of the cutaneous signs of DITRA is crucial for accurate diagnosis and timely administration of appropriate treatment. This review article provides a comprehensive overview of the current understanding of the cutaneous, non-cutaneous and histopathological manifestations of DITRA, with a focus on reported treatments. The disease typically presents in early childhood, although the age of onset can vary. Patients with DITRA exhibit recurrent episodes of skin inflammation, often with a pustular or pustular psoriasis-like appearance. Additionally, non-cutaneous manifestations are common, with recurrent fevers and elevated acute-phase reactants being the most prevalent. The exact prevalence of DITRA is unknown. Some cases of loss-of-function mutations in the IL36RN gene, considered a hallmark for diagnosis, have been identified in patients with familial generalized pustular psoriasis (GPP). Biological therapies with inhibition of IL-12/23 and IL-17 are promising treatment options; paediatric patients with DITRA have shown complete response with mild relapses. New and emerging biologic therapeutics targeting the IL-36 pathway are also of interest in the management of this rare autoinflammatory disorder.


Assuntos
Interleucinas , Psoríase , Humanos , Criança , Pré-Escolar , Interleucinas/genética , Pele/patologia , Psoríase/tratamento farmacológico , Psoríase/genética , Psoríase/patologia , Mutação , Inflamação
6.
Ann Pharmacother ; : 10600280241252688, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755971

RESUMO

OBJECTIVE: This article reviews clinical trial data that assesses the safety, efficacy, and clinical application of spesolimab, an interleukin-36 (IL-36) blocker, for the treatment of generalized pustular psoriasis (GPP). DATA SOURCES: A review of the literature was conducted using the search terms: "spesolimab," "BI 655130," and "spevigo" in MEDLINE (PubMed) and Clinicaltrials.gov from January 1, 1950 to October 31, 2023. STUDY SELECTION AND DATA EXTRACTION: Relevant articles in English relating to the pharmacodynamics, pharmacokinetics, efficacy, and safety of spesolimab were included. DATA SYNTHESIS: In one phase 2 clinical trial evaluating single dose IV spesolimab for GPP flares at day 8, 54% of patients receiving spesolimab had a GPP physician global assessment (GPPGA) pustulation subscore of 0, and 43% had a GPPGA total score of 0 compared with 6% and 11% for the placebo group, respectively. Another phase 2 clinical trial assessing subcutaneous spesolimab found 23% of patients in low-dose, 29% in medium-dose, and 10% of high-dose spesolimab had flares by week 48 compared with 52% of the placebo group. Hazard ratios for time to GPP flare compared with placebo were 0.16 (P = 0.0005), 0.35 (P = 0.0057), and 0.47 (P = 0.027) for the spesolimab groups, respectively. Infection rates were similar across treatment and placebo groups, and severe adverse events such as drug reactions with eosinophilia and systemic symptom (DRESS), cholelithiasis, and breast cancer occurred with spesolimab. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Spesolimab is a first-in-class IL-36 monoclonal antibody receptor antagonist approved for the treatment of acute GPP flares. It is a safe and effective therapeutic agent in preventing future GPP flares, with no current comparator trials with other GPP agents. CONCLUSION: Spesolimab is a safe and effective treatment for acute GPP flares in adults. Future clinical trials can establish safety and efficacy compared with other agents.

7.
Environ Res ; 243: 117813, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38043893

RESUMO

Terrestrial gross primary production (GPP) changes due to impervious surfaces significantly impact ecosystem services in watersheds. Understanding the asymmetric response of vegetation GPP to impervious surface expansion is essential for regional development planning and ecosystem management. However, the asymmetric response of vegetation GPP to the impacts of impervious surface expansion is unknown in different watersheds. This paper selected the Yellow River and Yangtze River basins as case studies. We characterized the overall change in GPP based on changes in impervious surface ratio (ISR), determined impervious surface expansion's direct and indirect impacts on GPP in the two watersheds, and further analyzed the asymmetric response of the compensatory effects of indirect influences on the impervious surface expansion in different watersheds. The results showed that: (1) The vegetation GPP decreased with increasing ISR in the Yangtze River Basin, while that in the Yellow River Basin first increased and then reduced. (2) The direct impacts of increased ISR reduced vegetation GPP, while the indirect impacts both had a growth-compensating effect. Growth compensation stabilized at approximately 0.40 and 0.30 in the Yellow and Yangtze River Basins. (3) When the ISR was 0.34-0.56, the growth compensation could offset the reduction of GPP due to direct impact and ensure that the background vegetation GPP was not damaged in the Yellow River Basin. In contrast, the background vegetation GPP was inevitably impaired with increased ISR in the Yangtze River Basin. Therefore, this study suggests that the ISR should be ensured to be between 0.34 and 0.56 to maximize the impervious surface of the Yellow River Basin without compromising the background vegetation GPP. While pursuing impervious surface expansion in the Yangtze River Basin, other programs should be sought to compensate for the loss to GPP.


Assuntos
Ecossistema , Monitoramento Ambiental , Rios , China
8.
Sensors (Basel) ; 24(10)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38794095

RESUMO

The introduction of fifth-generation (5G) mobile networks leads to an increase in energy consumption and higher operational costs for mobile network operators (MNOs). Consequently, the optimization of 5G networks' energy efficiency is crucial, both in terms of reducing MNO costs and in terms of the negative environmental impact. However, many aspects of the 5G mobile network technology itself have been standardized, including the 5G network slicing concept. This enables the creation of multiple independent logical 5G networks within the same physical infrastructure. Since the only necessary resources in 5G networks need to be used for the realization of a specific 5G network slice, the question of whether the implementation of 5G network slicing can contribute to the improvement of 5G and future sixth-generation networks' energy efficiency arises. To tackle this question, this review paper analyzes 5G network slicing and the energy demand of different network slicing use cases and mobile virtual network operator realizations based on network slicing. The paper also overviews standardized key performance indicators for the assessment of 5G network slices' energy efficiency and discusses energy efficiency in 5G network slicing lifecycle management. In particular, to show how efficient network slicing can optimize the energy consumption of 5G networks, versatile 5G network slicing use case scenarios, approaches, and resource allocation concepts in the space, time, and frequency domains have been discussed, including artificial intelligence-based implementations of network slicing. The results of the comprehensive discussion indicate that the different implementations and approaches to network slicing pave the way for possible further reductions in 5G MNO energy costs and carbon dioxide emissions in the future.

9.
Sensors (Basel) ; 24(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38400455

RESUMO

This paper delves into an interference analysis, focusing on the forthcoming Starlink Generation 2 satellites, stated to operate within the 1990-1995 MHz frequency band. The aim is to assess the potential interference from this Starlink system to the satellite receivers of mobile satellite systems (MSSs), which are set to function within the 1980-2010 MHz range, and satellite receivers of the NTN systems, which are planned to operate in the n256 bands, defined by the 3GPP specifications. Through simulation-based evaluations, both single-entry and aggregate interference levels from Starlink to MSSs and NTN systems are comprehensively explored. To estimate the interference impact, several protection criteria were used. The study is in line with the Recommendations of International Telecommunication Union (ITU-R) and common approaches that are used when performing compatibility studies between satellite systems. The findings of this study demonstrate the feasibility of utilizing the n25 band for NTN direct-to-device services.

10.
J Environ Manage ; 351: 119756, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38103422

RESUMO

Governments globally face increasing pressure from climate advocates and international agreements, such as the Paris Agreement, to enact policies addressing climate change. This paper addresses the imperative for sustainable practices outlined in such agreements, with a specific focus on assessing the drivers of Green Procurement Practices (GPP) within Public Sector Organizations (PSOs). A dearth of research exists in systematically analyzing and prioritizing these drivers, exploring their interdependencies, and elucidating their relative importance. GPP is pivotal in market transformation by promoting environmentally friendly products and endorsing low-carbon, energy-efficient alternatives. This, in turn, contributes significantly to mitigating climate change and fostering a shift towards a greener, more sustainable economy. Identification of the drivers has been performed by an extensive review of the literature combined with the author's viewpoint, while the analysis has been performed using the novel method of Dominance-based Rough Set Approach (DRSA) and Interpretive Structural Modelling (ISM) with Matriced' Impacts Croise's Multiplication Applique'e a UN Classement (MICMAC) analysis. The study's outcome reveals that the Demand for Eco-friendly products is the primary driver for the incorporation of GPP, followed by the drivers' Presence of guidelines support and Government Regulations. Findings of the research also demonstrate that suppliers' propensity to adopt green practices depends on several factors, including sustainable supplier cooperation, degree of commitment to embrace green initiatives, government interventions in the form of incentives and guidelines support, and the presence of a legal framework. The findings of this research will enrich the understanding of policymakers and managers to formulate strategies for advancing GPP structured and sustainable implementation in PSOs. The study's findings will also benefit green technology sector advancement through the widespread adoption of GPP.


Assuntos
Organizações , Setor Público , Governo , Motivação , Paris
11.
Am J Hum Genet ; 107(3): 539-543, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758448

RESUMO

The identification of disease alleles underlying human autoinflammatory diseases can provide important insights into the mechanisms that maintain neutrophil homeostasis. Here, we focused our attention on generalized pustular psoriasis (GPP), a potentially life-threatening disorder presenting with cutaneous and systemic neutrophilia. Following the whole-exome sequencing of 19 unrelated affected individuals, we identified a subject harboring a homozygous splice-site mutation (c.2031-2A>C) in MPO. This encodes myeloperoxidase, an essential component of neutrophil azurophil granules. MPO screening in conditions phenotypically related to GPP uncovered further disease alleles in one subject with acral pustular psoriasis (c.2031-2A>C;c.2031-2A>C) and in two individuals with acute generalized exanthematous pustulosis (c.1705C>T;c.2031-2A>C and c.1552_1565del;c.1552_1565del). A subsequent analysis of UK Biobank data demonstrated that the c.2031-2A>C and c.1705C>T (p.Arg569Trp) disease alleles were also associated with increased neutrophil abundance in the general population (p = 5.1 × 10-6 and p = 3.6 × 10-5, respectively). The same applied to three further deleterious variants that had been genotyped in the cohort, with two alleles (c.995C>T [p.Ala332Val] and c.752T>C [p.Met251Thr]) yielding p values < 10-10. Finally, treatment of healthy neutrophils with an MPO inhibitor (4-Aminobenzoic acid hydrazide) increased cell viability and delayed apoptosis, highlighting a mechanism whereby MPO mutations affect granulocyte numbers. These findings identify MPO as a genetic determinant of pustular skin disease and neutrophil abundance. Given the recent interest in the development of MPO antagonists for the treatment of neurodegenerative disease, our results also suggest that the pro-inflammatory effects of these agents should be closely monitored.


Assuntos
Doenças Neurodegenerativas/genética , Peroxidase/genética , Psoríase/genética , Dermatopatias/genética , Ácido 4-Aminobenzoico/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular/efeitos dos fármacos , Feminino , Genótipo , Humanos , Mutação com Perda de Função/genética , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/patologia , Neutrófilos/efeitos dos fármacos , Peroxidase/antagonistas & inibidores , Fenótipo , Psoríase/tratamento farmacológico , Psoríase/patologia , Pele/efeitos dos fármacos , Pele/patologia , Dermatopatias/tratamento farmacológico , Dermatopatias/patologia
12.
Am J Hum Genet ; 107(3): 527-538, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758447

RESUMO

Generalized pustular psoriasis (GPP) is a severe multi-systemic inflammatory disease characterized by neutrophilic pustulosis and triggered by pro-inflammatory IL-36 cytokines in skin. While 19%-41% of affected individuals harbor bi-allelic mutations in IL36RN, the genetic cause is not known in most cases. To identify and characterize new pathways involved in the pathogenesis of GPP, we performed whole-exome sequencing in 31 individuals with GPP and demonstrated effects of mutations in MPO encoding the neutrophilic enzyme myeloperoxidase (MPO). We discovered eight MPO mutations resulting in MPO -deficiency in neutrophils and monocytes. MPO mutations, primarily those resulting in complete MPO deficiency, cumulatively associated with GPP (p = 1.85E-08; OR = 6.47). The number of mutant MPO alleles significantly differed between 82 affected individuals and >4,900 control subjects (p = 1.04E-09); this effect was stronger when including IL36RN mutations (1.48E-13) and correlated with a younger age of onset (p = 0.0018). The activity of four proteases, previously implicated as activating enzymes of IL-36 precursors, correlated with MPO deficiency. Phorbol-myristate-acetate-induced formation of neutrophil extracellular traps (NETs) was reduced in affected cells (p = 0.015), and phagocytosis assays in MPO-deficient mice and human cells revealed altered neutrophil function and impaired clearance of neutrophils by monocytes (efferocytosis) allowing prolonged neutrophil persistence in inflammatory skin. MPO mutations contribute significantly to GPP's pathogenesis. We implicate MPO as an inflammatory modulator in humans that regulates protease activity and NET formation and modifies efferocytosis. Our findings indicate possible implications for the application of MPO inhibitors in cardiovascular diseases. MPO and affected pathways represent attractive targets for inducing resolution of inflammation in neutrophil-mediated skin diseases.


Assuntos
Inflamação/genética , Interleucinas/genética , Peroxidase/genética , Psoríase/genética , Dermatopatias/genética , Adulto , Animais , Citocinas/genética , Armadilhas Extracelulares/genética , Feminino , Humanos , Inflamação/patologia , Interleucina-1/genética , Interleucinas/metabolismo , Masculino , Camundongos , Mutação/genética , Neutrófilos/metabolismo , Psoríase/patologia , Doenças Raras/enzimologia , Doenças Raras/genética , Doenças Raras/patologia , Pele/enzimologia , Pele/patologia , Dermatopatias/patologia
13.
New Phytol ; 240(3): 984-1002, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37583086

RESUMO

Land carbon dynamics in temperate and boreal ecosystems are sensitive to environmental change. Accurately simulating gross primary productivity (GPP) and its seasonality is key for reliable carbon cycle projections. However, significant biases have been found in early spring GPP simulations of northern forests, where observations often suggest a later resumption of photosynthetic activity than predicted by models. Here, we used eddy covariance-based GPP estimates from 39 forest sites that differ by their climate and dominant plant functional types. We used a mechanistic and an empirical light use efficiency (LUE) model to investigate the magnitude and environmental controls of delayed springtime photosynthesis resumption (DSPR) across sites. We found DSPR reduced ecosystem LUE by 30-70% at many, but not all site-years during spring. A significant depression of LUE was found not only in coniferous but also at deciduous forests and was related to combined high radiation and low minimum temperatures. By embedding cold-acclimation effects on LUE that considers the delayed effects of minimum temperatures, initial model bias in simulated springtime GPP was effectively resolved. This provides an approach to improve GPP estimates by considering physiological acclimation and enables more reliable simulations of photosynthesis in northern forests and projections in a warming climate.

14.
Glob Chang Biol ; 29(17): 4750-4757, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37381593

RESUMO

Climate change leads to increasing temperature and more extreme hot and drought events. Ecosystem capability to cope with climate warming depends on vegetation's adjusting pace with temperature change. How environmental stresses impair such a vegetation pace has not been carefully investigated. Here we show that dryness substantially dampens vegetation pace in warm regions to adjust the optimal temperature of gross primary production (GPP) ( T opt GPP ) in response to change in temperature over space and time. T opt GPP spatially converges to an increase of 1.01°C (95% CI: 0.97, 1.05) per 1°C increase in the yearly maximum temperature (Tmax ) across humid or cold sites worldwide (37o S-79o N) but only 0.59°C (95% CI: 0.46, 0.74) per 1°C increase in Tmax across dry and warm sites. T opt GPP temporally changes by 0.81°C (95% CI: 0.75, 0.87) per 1°C interannual variation in Tmax at humid or cold sites and 0.42°C (95% CI: 0.17, 0.66) at dry and warm sites. Regardless of the water limitation, the maximum GPP (GPPmax ) similarly increases by 0.23 g C m-2 day-1 per 1°C increase in T opt GPP in either humid or dry areas. Our results indicate that the future climate warming likely stimulates vegetation productivity more substantially in humid than water-limited regions.


Assuntos
Mudança Climática , Plantas , Estresse Fisiológico , Temperatura , Secas , Ecossistema
15.
Glob Chang Biol ; 29(14): 3924-3940, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37165918

RESUMO

Forests are increasingly exposed to extreme global warming-induced climatic events. However, the immediate and carry-over effects of extreme events on forests are still poorly understood. Gross primary productivity (GPP) capacity is regarded as a good proxy of the ecosystem's functional stability, reflecting its physiological response to its surroundings. Using eddy covariance data from 34 forest sites in the Northern Hemisphere, we analyzed the immediate and carry-over effects of late-spring frost (LSF) and growing season drought on needle-leaf and broadleaf forests. Path analysis was applied to reveal the plausible reasons behind the varied responses of forests to extreme events. The results show that LSF had clear immediate effects on the GPP capacity of both needle-leaf and broadleaf forests. However, GPP capacity in needle-leaf forests was more sensitive to drought than in broadleaf forests. There was no interaction between LSF and drought in either needle-leaf or broadleaf forests. Drought effects were still visible when LSF and drought coexisted in needle-leaf forests. Path analysis further showed that the response of GPP capacity to drought differed between needle-leaf and broadleaf forests, mainly due to the difference in the sensitivity of canopy conductance. Moreover, LSF had a more severe and long-lasting carry-over effect on forests than drought. These results enrich our understanding of the mechanisms of forest response to extreme events across forest types.


Assuntos
Secas , Ecossistema , Estações do Ano , Florestas , Aquecimento Global , Mudança Climática , Árvores
16.
Exp Dermatol ; 32(8): 1204-1218, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36779681

RESUMO

Generalized pustular psoriasis (GPP) is a rare subset of psoriasis involving episodes of sterile pustules accompanied by inflammation and, often, systemic involvement. The inflammatory nature of GPP has potential for severe multisystem complications including high-output cardiac failure, infections, digestive system issues, and disfiguring or lethal acute flare episodes. The disease tends to have higher prevalence in females and Asians. The IL-1/IL-36 inflammatory pathway is a critical facet of GPP's pathology. Genetic mutations that are associated with GPP include modifications of Interleukin 36 Receptor Antagonist (IL36RN), Caspase Recruitment Domain Family Member 14 (CARD14), Adaptor Related Protein Complex 1 Subunit Sigma 3 (AP1S3), Myeloperoxidase (MPO) and Serpin Peptidase Inhibitor Clade A Member 3 (SERPINA3) genes. Treatment guidelines for GPP are not well-entrenched. Currently, only one GPP-specific treatment, the interleukin-36 receptor antagonist (IL-36Ra) spesolimab, has been approved for use in the United States. Additional anti-IL-36 pathway therapies are currently being developed. Other treatment options include other biologic therapies such as IL-17 inhibitors, IL-23 inhibitors and TNFα inhibitors. Non-biologic therapeutic options include retinoids, cyclosporine and methotrexate. Treatment options differ throughout the world; most countries utilize retinoids, cyclosporine and methotrexate as first-line non-biologic options. China and United Kingdom have no GPP-specific biologic therapies approved for use, while several biologic therapies are approved for use in Japan. This review aims to serve as an update on the current global management of GPP while also including relevant aspects of disease pathogenesis, diagnosis, clinical presentation, histopathology, aetiology and epidemiology.


Assuntos
Psoríase , Dermatopatias Vesiculobolhosas , Feminino , Humanos , Interleucinas/genética , Metotrexato/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/diagnóstico , Ciclosporina/uso terapêutico , Doença Aguda , Doença Crônica , Retinoides , Guanilato Ciclase , Proteínas de Membrana , Proteínas Adaptadoras de Sinalização CARD/genética
17.
J Am Acad Dermatol ; 89(1): 36-44, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36870370

RESUMO

BACKGROUND: Effisayil 1 was a randomized, placebo-controlled study of spesolimab, which is an anti-IL-36 receptor antibody, in patients presenting with a generalized pustular psoriasis flare. OBJECTIVE: To assess the effects of spesolimab over the 12-week study. METHODS: The primary endpoint of the study was Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at week 1. Patients (N = 53) were randomized (2:1) to receive a single intravenous dose of 900 mg spesolimab or placebo on day 1. Patients could receive open-label spesolimab for persistent flare symptoms on day 8. RESULTS: Most patients receiving spesolimab achieved a GPPGA pustulation subscore of 0 (60.0%) and GPPGA total score of 0 or 1 (60.0%) by week 12. In patients randomized to placebo who received open-label spesolimab on day 8, the proportion with GPPGA pustulation subscore of 0 increased from 5.6% at day 8 to 83.3% at week 2. No factors predictive of spesolimab response were identified in patient demographics or clinical characteristics. LIMITATIONS: The effect of initial randomization was not determined conventionally beyond week 1 due to patients receiving open-label spesolimab. CONCLUSION: Rapid control of generalized pustular psoriasis flare symptoms with spesolimab was sustained over 12 weeks, further supporting its potential use as a therapeutic option for patients.


Assuntos
Psoríase , Humanos , Resultado do Tratamento , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego
18.
Proc Natl Acad Sci U S A ; 117(17): 9216-9222, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32284402

RESUMO

Terrestrial photosynthesis is regulated by plant phenology and environmental conditions, both of which experienced substantial changes in recent decades. Unlike early-season photosynthesis, which is mostly driven by temperature or wet-season onset, late-season photosynthesis can be limited by several factors and the underlying mechanisms are less understood. Here, we analyze the temperature and water limitations on the ending date of photosynthesis (EOP), using data from both remote-sensing and flux tower-based measurements. We find a contrasting spatial pattern of temperature and water limitations on EOP. The threshold separating these is determined by the balance between energy availability and soil water supply. This coordinated temperature and moisture regulation can be explained by "law of minimum," i.e., as temperature limitation diminishes, higher soil water is needed to support increased vegetation activity, especially during the late growing season. Models project future warming and drying, especially during late season, both of which should further expand the water-limited regions, causing large variations and potential decreases in photosynthesis.


Assuntos
Clorofila/análise , Fotossíntese/fisiologia , Água/metabolismo , Ciclo do Carbono/fisiologia , Ecossistema , Monitoramento Ambiental/métodos , Florestas , Plantas/metabolismo , Imagens de Satélites , Estações do Ano , Solo/química , Luz Solar , Temperatura
19.
Sensors (Basel) ; 23(4)2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36850858

RESUMO

Cellular vehicle-to-everything (C-V2X) is one of the enabling vehicular communication technologies gaining momentum from the standardization bodies, industry, and researchers aiming to realize fully autonomous driving and intelligent transportation systems. The 3rd Generation Partnership Project (3GPP) standardization body has actively been developing the standards evolving from 4G-V2X to 5G-V2X providing ultra-reliable low-latency communications and higher throughput to deliver the solutions for advanced C-V2X services. In this survey, we analyze the 3GPP standard documents relevant to V2X communication to present the complete vision of 3GPP-enabled C-V2X. To better equip the readers with knowledge of the topic, we describe the underlying concepts and an overview of the evolution of 3GPP C-V2X standardization. Furthermore, we provide the details of the enabling concepts for V2X support by 3GPP. In this connection, we carry out an exhaustive study of the 3GPP standard documents and provide a logical taxonomy of C-V2X related 3GPP standard documents divided into three categories: 4G, 4G & 5G, and 5G based V2X services. We provide a detailed analysis of these categories discussing the system architecture, network support, key issues, and potential solution approaches supported by the 3GPP. We also highlight the gap and the need for intelligence in the execution of different operations to enable the use-case scenarios of Level-5 autonomous driving. We believe, the paper will equip readers to comprehend the technological standards for the delivery of different ITS services of the higher level of autonomous driving.

20.
Sensors (Basel) ; 23(22)2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-38005426

RESUMO

Five countries in the Lancang-Mekong region, including Myanmar, Laos, Thailand, Cambodia, and Vietnam, are facing the threat of deforestation, despite having a high level of forest coverage. Quantitatively assessing the forest ecosystem status and its variations based on remote sensing products for vegetation parameters is a crucial prerequisite for the ongoing phase of our future project. In this study, we analyzed forest health in the year 2020 using four vegetation indicators: forest coverage index (FCI), leaf area index (LAI), fraction of green vegetation cover (FVC), and gross primary productivity (GPP). Additionally, we introduced an ecosystem quality index (EQI) to assess the quality of forest health. To understand the long-term trends in the vegetation indicators and EQI, we also performed a linear regression analysis from 2010 to 2020. The results revealed that Laos ranked as the top-performing country for forest ecosystem status in the Lancang-Mekong region in 2020. However, the long-term trend analysis results showed that Cambodia experienced the most significant decline across all indicators, while Vietnam and Thailand demonstrated varying degrees of improvement. This study provides a quality assessment of forest health and its variations in the Lancang-Mekong region, which is crucial for implementing effective conservation strategies.


Assuntos
Ecossistema , Tecnologia de Sensoriamento Remoto , Florestas , Camboja , Tailândia
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