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1.
Proc Natl Acad Sci U S A ; 121(6): e2309333121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38289951

RESUMO

We present improved estimates of air-sea CO2 exchange over three latitude bands of the Southern Ocean using atmospheric CO2 measurements from global airborne campaigns and an atmospheric 4-box inverse model based on a mass-indexed isentropic coordinate (Mθe). These flux estimates show two features not clearly resolved in previous estimates based on inverting surface CO2 measurements: a weak winter-time outgassing in the polar region and a sharp phase transition of the seasonal flux cycles between polar/subpolar and subtropical regions. The estimates suggest much stronger summer-time uptake in the polar/subpolar regions than estimates derived through neural-network interpolation of pCO2 data obtained with profiling floats but somewhat weaker uptake than a recent study by Long et al. [Science 374, 1275-1280 (2021)], who used the same airborne data and multiple atmospheric transport models (ATMs) to constrain surface fluxes. Our study also uses moist static energy (MSE) budgets from reanalyses to show that most ATMs tend to have excessive diabatic mixing (transport across moist isentrope, θe, or Mθe surfaces) at high southern latitudes in the austral summer, which leads to biases in estimates of air-sea CO2 exchange. Furthermore, we show that the MSE-based constraint is consistent with an independent constraint on atmospheric mixing based on combining airborne and surface CO2 observations.

2.
Environ Sci Technol ; 57(13): 5117-5124, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-36930700

RESUMO

Coral reefs host some of the highest concentrations of biodiversity and economic value in the oceans, yet these ecosystems are under threat due to climate change and other human impacts. Reef monitoring is routinely used to help prioritize reefs for conservation and evaluate the success of intervention efforts. Reef status and health are most frequently characterized using diver-based surveys, but the inherent limitations of these methods mean there is a growing need for advanced, standardized, and automated reef techniques that capture the complex nature of the ecosystem. Here we draw on experiences from our own interdisciplinary research programs to describe advances in in situ diver-based and autonomous reef monitoring. We present our vision for integrating interdisciplinary measurements for select "case-study" reefs worldwide and for learning patterns within the biological, physical, and chemical reef components and their interactions. Ultimately, these efforts could support the development of a scalable and standardized suite of sensors that capture and relay key data to assist in categorizing reef health. This framework has the potential to provide stakeholders with the information necessary to assess reef health during an unprecedented time of reef change as well as restoration and intervention activities.


Assuntos
Antozoários , Recifes de Corais , Animais , Humanos , Ecossistema , Biodiversidade , Oceanos e Mares , Conservação dos Recursos Naturais/métodos
3.
Am J Respir Cell Mol Biol ; 66(5): 555-563, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35157553

RESUMO

Acute respiratory distress syndrome (ARDS) remains a significant problem in need of new pharmaceutical approaches to improve its resolution. Studies comparing gene expression signatures in rodents and humans with lung injury reveal conserved pathways, including MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-related protein kinase) activation. In preclinical acute lung injury (ALI) models, inhibition of MAP2K1 (MAPK kinase 1)/MAP2K2 (MAPK kinase 2) improves measures of ALI. Myeloid cell deletion of MAP2K1 results in sustained MAP2K2 activation and nonresolving ALI, suggesting that MAP2K2 deactivation may be a key driver of ALI resolution. We used human genomic data from the iSPAAR (Identification of SNPs Predisposing to Altered Acute Lung Injury Risk) Consortium to assess genetic variants in MAP2K1 and MAP2K2 for association with mortality from ARDS. To determine the role of MAP2K2 in ALI recovery, we studied mice deficient in Map2k2 (Mek2-/-) and wild-type control mice in ALI models. We identified a MAP2K2 variant that was associated with death in ARDS and MAP2K2 expression. In Pseudomonas aeruginosa ALI, Mek2-/- mice had similar early alveolar neutrophilic recruitment but faster resolution of alveolar neutrophilia and vascular leak. Gene expression analysis revealed a role for MAP2K2 in promoting and sustaining select proinflammatory pathway activation in ALI. Bone marrow chimera studies indicate that leukocyte MAP2K2 is the key regulator of ALI duration. These studies implicate a role for MAP2K2 in ALI duration via transcriptional regulation of inflammatory programming with potential relevance to ARDS. Targeting leukocyte MAP2K2 may be an effective strategy to promote ALI resolution.


Assuntos
Lesão Pulmonar Aguda , MAP Quinase Quinase 2/metabolismo , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica , MAP Quinase Quinase 2/genética , Camundongos , Síndrome do Desconforto Respiratório/genética
4.
Glob Chang Biol ; 28(7): 2236-2258, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34931401

RESUMO

Climate impacts are not always easily discerned in wild populations as detecting climate change signals in populations is challenged by stochastic noise associated with natural climate variability, variability in biotic and abiotic processes, and observation error in demographic rates. Detection of the impact of climate change on populations requires making a formal distinction between signals in the population associated with long-term climate trends from those generated by stochastic noise. The time of emergence (ToE) identifies when the signal of anthropogenic climate change can be quantitatively distinguished from natural climate variability. This concept has been applied extensively in the climate sciences, but has not been explored in the context of population dynamics. Here, we outline an approach to detecting climate-driven signals in populations based on an assessment of when climate change drives population dynamics beyond the envelope characteristic of stochastic variations in an unperturbed state. Specifically, we present a theoretical assessment of the time of emergence of climate-driven signals in population dynamics ( ToE pop ). We identify the dependence of ToE pop on the magnitude of both trends and variability in climate and also explore the effect of intrinsic demographic controls on ToE pop . We demonstrate that different life histories (fast species vs. slow species), demographic processes (survival, reproduction), and the relationships between climate and demographic rates yield population dynamics that filter climate trends and variability differently. We illustrate empirically how to detect the point in time when anthropogenic signals in populations emerge from stochastic noise for a species threatened by climate change: the emperor penguin. Finally, we propose six testable hypotheses and a road map for future research.


Assuntos
Mudança Climática , Spheniscidae , Animais , Dinâmica Populacional , Reprodução
5.
Clin Sci (Lond) ; 136(10): 747-769, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35621124

RESUMO

Pneumonia and its sequelae, acute lung injury, present unique challenges for pulmonary and critical care healthcare professionals, and these challenges have recently garnered global attention due to the ongoing Sars-CoV-2 pandemic. One limitation to translational investigation of acute lung injury, including its most severe manifestation (acute respiratory distress syndrome, ARDS) has been heterogeneity resulting from the clinical and physiologic diagnosis that represents a wide variety of etiologies. Recent efforts have improved our understanding and approach to heterogeneity by defining sub-phenotypes of ARDS although significant gaps in knowledge remain. Improving our mechanistic understanding of acute lung injury and its most common cause, infectious pneumonia, can advance our approach to precision targeted clinical interventions. Here, we review the pathogenesis of pneumonia and acute lung injury, including how respiratory infections and lung injury disrupt lung homoeostasis, and provide an overview of respiratory microbial pathogenesis, the lung microbiome, and interventions that have been demonstrated to improve outcomes-or not-in human clinical trials.


Assuntos
Lesão Pulmonar Aguda , COVID-19 , Pneumonia , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Humanos , Síndrome do Desconforto Respiratório/etiologia , SARS-CoV-2
6.
Nature ; 530(7591): 469-72, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-26911782

RESUMO

The ocean has absorbed 41 per cent of all anthropogenic carbon emitted as a result of fossil fuel burning and cement manufacture. The magnitude and the large-scale distribution of the ocean carbon sink is well quantified for recent decades. In contrast, temporal changes in the oceanic carbon sink remain poorly understood. It has proved difficult to distinguish between air-to-sea carbon flux trends that are due to anthropogenic climate change and those due to internal climate variability. Here we use a modelling approach that allows for this separation, revealing how the ocean carbon sink may be expected to change throughout this century in different oceanic regions. Our findings suggest that, owing to large internal climate variability, it is unlikely that changes in the rate of anthropogenic carbon uptake can be directly observed in most oceanic regions at present, but that this may become possible between 2020 and 2050 in some regions.


Assuntos
Dióxido de Carbono/análise , Sequestro de Carbono , Mudança Climática/estatística & dados numéricos , Observação , Água do Mar/química , Atmosfera/química , Ciclo do Carbono , Ecossistema , Atividades Humanas , Modelos Teóricos , Oceanos e Mares , Fatores de Tempo
7.
Proc Biol Sci ; 288(1963): 20211337, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34814747

RESUMO

Climate change has led to phenological shifts in many species, but with large variation in magnitude among species and trophic levels. The poster child example of the resulting phenological mismatches between the phenology of predators and their prey is the great tit (Parus major), where this mismatch led to directional selection for earlier seasonal breeding. Natural climate variability can obscure the impacts of climate change over certain periods, weakening phenological mismatching and selection. Here, we show that selection on seasonal timing indeed weakened significantly over the past two decades as increases in late spring temperatures have slowed down. Consequently, there has been no further advancement in the date of peak caterpillar food abundance, while great tit phenology has continued to advance, thereby weakening the phenological mismatch. We thus show that the relationships between temperature, phenologies of prey and predator, and selection on predator phenology are robust, also in times of a slowdown of warming. Using projected temperatures from a large ensemble of climate simulations that take natural climate variability into account, we show that prey phenology is again projected to advance faster than great tit phenology in the coming decades, and therefore that long-term global warming will intensify phenological mismatches.


Assuntos
Aquecimento Global , Passeriformes , Animais , Mudança Climática , Reprodução , Estações do Ano , Temperatura
8.
Global Biogeochem Cycles ; 34(8): e2019GB006453, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32999530

RESUMO

Anthropogenically forced changes in ocean biogeochemistry are underway and critical for the ocean carbon sink and marine habitat. Detecting such changes in ocean biogeochemistry will require quantification of the magnitude of the change (anthropogenic signal) and the natural variability inherent to the climate system (noise). Here we use Large Ensemble (LE) experiments from four Earth system models (ESMs) with multiple emissions scenarios to estimate Time of Emergence (ToE) and partition projection uncertainty for anthropogenic signals in five biogeochemically important upper-ocean variables. We find ToEs are robust across ESMs for sea surface temperature and the invasion of anthropogenic carbon; emergence time scales are 20-30 yr. For the biological carbon pump, and sea surface chlorophyll and salinity, emergence time scales are longer (50+ yr), less robust across the ESMs, and more sensitive to the forcing scenario considered. We find internal variability uncertainty, and model differences in the internal variability uncertainty, can be consequential sources of uncertainty for projecting regional changes in ocean biogeochemistry over the coming decades. In combining structural, scenario, and internal variability uncertainty, this study represents the most comprehensive characterization of biogeochemical emergence time scales and uncertainty to date. Our findings delineate critical spatial and duration requirements for marine observing systems to robustly detect anthropogenic change.

9.
Limnol Oceanogr ; 65(2): 314-324, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32139946

RESUMO

Gas ebullition from aquatic systems to the atmosphere represents a potentially important fraction of primary production that goes unquantified by measurements of dissolved gas concentrations. Although gas ebullition from photosynthetic surfaces has often been observed, it is rarely quantified. The resulting underestimation of photosynthetic activity may significantly bias the determination of ecosystem trophic status and estimated rates of biogeochemical cycling from in situ measures of dissolved oxygen. Here, we quantified gas ebullition rates in Zostera marina meadows in Virginia, U.S.A. using simple funnel traps and analyzed the oxygen concentration and isotopic composition of the captured gas. Maximum hourly rates of oxygen ebullition (3.0 mmol oxygen m-2 h-1) were observed during the coincidence of high irradiance and low tides, particularly in the afternoon when oxygen and temperature maxima occurred. The daily ebullition fluxes (up to 11 mmol oxygen m-2 d-1) were roughly equivalent to net primary production rates determined from dissolved oxygen measurements indicating that bubble ebullition can represent a major component of primary production that is not commonly included in ecosystem-scale estimates. Oxygen content comprised 20-40% of the captured bubble gas volume and correlated negatively with its δ18O values, consistent with a predominance of mixing between the higher δ18O of atmospheric oxygen in equilibrium with seawater and the lower δ18O of oxygen derived from photosynthesis. Thus, future studies interested in the metabolism of highly productive, shallow water ecosystems, and particularly those measuring in situ oxygen flux, should not ignore the bubble formation and ebullition processes described here.

10.
J Allergy Clin Immunol ; 143(4): 1536-1548, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30445062

RESUMO

BACKGROUND: Macrophage plasticity allows cells to adopt different phenotypes, a property with important implications in disorders such as cystic fibrosis (CF) and asthma. OBJECTIVE: We sought to examine the transcriptional and functional significance of macrophage repolarization from an M1 to an M2 phenotype and assess the role of a common human genetic disorder (CF) and a prototypical allergic disease (asthma) in this transformation. METHODS: Monocyte-derived macrophages were collected from healthy subjects and patients with CF and polarized to an M2 state by using IL-4, IL-10, glucocorticoids, apoptotic PMNs, or azithromycin. We performed transcriptional profiling and pathway analysis for each stimulus. We assessed the ability of M2-repolarized macrophages to respond to LPS rechallenge and clear apoptotic neutrophils and used murine models to determine conserved functional responses to IL-4 and IL-10. We investigated whether M2 signatures were associated with alveolar macrophage phenotypes in asthmatic patients. RESULTS: We found that macrophages exhibit highly diverse responses to distinct M2-polarizing stimuli. Specifically, IL-10 activated proinflammatory pathways and abrogated LPS tolerance, allowing rapid restoration of LPS responsiveness. In contrast, IL-4 enhanced LPS tolerance, dampening proinflammatory responses after repeat LPS challenge. A common theme observed across all M2 stimuli was suppression of interferon-associated pathways. We found that CF macrophages had intact reparative and transcriptional responses, suggesting that macrophage contributions to CF-related lung disease are primarily shaped by their environment. Finally, we leveraged in vitro-derived signatures to show that allergen provocation induces distinct M2 state transcriptional patterns in alveolar macrophages. CONCLUSION: Our findings highlight the diversity of macrophage polarization, attribute functional consequences to different M2 stimuli, and provide a framework to phenotype macrophages in disease states.


Assuntos
Asma/imunologia , Fibrose Cística/imunologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Adulto , Animais , Citocinas/imunologia , Feminino , Humanos , Masculino , Camundongos , Fenótipo , Transcrição Gênica , Transcriptoma
11.
Reprod Biol Endocrinol ; 17(1): 81, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31647034

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with important factors that influence fetal development. Sphingolipids are known to be associated with the development of diabetes. Our objective was to examine ceramide, a key sphingolipid, hyperosmolarity, and apoptosis in placentas from GDM patients treated with insulin or diet. METHODS: Ceramide levels were assessed in placental tissues using immunohistochemistry. Immunoblot was performed to quantify serine palmitoyltransferase (SPT), the rate-limiting enzyme in ceramide biosynthesis, NFAT5, SMIT, AR, caspase 3 and the X-linked inhibitor of apoptosis. Trophoblast cells were treated with insulin or ceramide and assessments for mitochondrial respiration, caspase 3 and XIAP were also performed. RESULTS: Immunohistochemistry showed increased ceramides in the placental villous trophoblasts of the insulin-treated GDM patients. Nuclear SPT was upregulated only in the insulin-treated GDM placenta when compared to controls. Nuclear NFAT5 was also increased in the GDM placenta. Active caspase 3 was elevated in placentas from both insulin- and diet-treated GDM patients. Mitochondrial respiration was decreased in trophoblasts treated with ceramide. Active caspase was not changed while XIAP protein was increased in trophoblasts treated with ceramide. CONCLUSIONS: Our findings confirm the presence of ceramide in the human placenta of control and GDM patients. Furthermore, we conclude that ceramide is increased in the placental trophoblast during insulin treatment and that its upregulation correlates with elevated NFAT5, SMIT, increased apoptosis and decreased trophoblast mitochondrial respiration.


Assuntos
Ceramidas/metabolismo , Diabetes Gestacional/metabolismo , Mitocôndrias/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Adulto , Apoptose/efeitos dos fármacos , Ceramidas/farmacologia , Diabetes Gestacional/tratamento farmacológico , Dieta , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Gravidez , Serina C-Palmitoiltransferase/metabolismo , Trofoblastos/efeitos dos fármacos , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
12.
J Immunol ; 198(2): 862-872, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-28003382

RESUMO

Macrophages have important functional roles in regulating the timely promotion and resolution of inflammation. Although many of the intracellular signaling pathways involved in the proinflammatory responses of macrophages are well characterized, the components that regulate macrophage reparative properties are less well understood. We identified the MEK1/2 pathway as a key regulator of macrophage reparative properties. Pharmacological inhibition of the MEK1/2 pathway by a MEK1/2 inhibitor (MEKi) significantly increased expression of IL-4/IL-13 (M2)-responsive genes in murine bone marrow-derived and alveolar macrophages. Deletion of the MEK1 gene using LysMCre+/+Mek1fl/fl macrophages as an alternate approach yielded similar results. MEKi enhanced STAT6 phosphorylation, and MEKi-induced changes in M2 polarization were dependent on STAT6. In addition, MEKi treatment significantly increased murine and human macrophage efferocytosis of apoptotic cells, independent of macrophage polarization and STAT6. These phenotypes were associated with increased gene and protein expression of Mertk, Tyro3, and Abca1, three proteins that promote macrophage efferocytosis. We also studied the effects of MEKi on in vivo macrophage efferocytosis and polarization. MEKi-treated mice had increased efferocytosis of apoptotic polymorphonuclear leukocytes instilled into the peritoneum. Furthermore, administration of MEKi after LPS-induced lung injury led to improved recovery of weight, fewer neutrophils in the alveolar compartment, and greater macrophage M2 polarization. Collectively, these results show that MEK1/2 inhibition is capable of promoting the reparative properties of murine and human macrophages. These studies suggest that the MEK1/2 pathway may be a therapeutic target to promote the resolution of inflammation via modulation of macrophage functions.


Assuntos
MAP Quinase Quinase 1/imunologia , MAP Quinase Quinase 2/imunologia , Macrófagos/imunologia , Fagocitose/imunologia , Transdução de Sinais/imunologia , Animais , Western Blotting , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Humanos , MAP Quinase Quinase 1/antagonistas & inibidores , MAP Quinase Quinase 2/antagonistas & inibidores , Macrófagos/enzimologia , Camundongos , Reação em Cadeia da Polimerase
13.
Psychiatr Q ; 90(1): 117-128, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30328020

RESUMO

Given that there is a lack of instruments assessing internet-related addictions among Chinese population, this study aimed to validate the Chinese version of the nine-item Internet Gaming Disorder Scales- Short Form (IGDS-SF9), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application-Based Addiction Scale (SABAS) among Hong Kong university students. Participants aged between 17 and 30 years participated in the present study (n = 307; 32.4% males; mean [SD] age = 21.64 [8.11]). All the participants completed the IGDS-SF9, BSMAS, SABAS, and the Hospital Anxiety and Depression Scale (HADS). Confirmatory factor analyses (CFAs) were used to examine the factorial structures and the unidimensionality for IGDS-SF9, BSMAS, and SABAS. CFAs demonstrated that the three scales were all unidimensional with satisfactory fit indices: comparative fit index = 0.969 to 0.992. In addition, the IGDS-SF9 and BSMAS were slightly modified based on the modification index in CFA. The Chinese IGDS-SF9, BSMAS, and SABAS are valid instruments to assess the addiction levels of internet-related activities for Hong Kong university students.


Assuntos
Comportamento Aditivo/diagnóstico , Internet , Escalas de Graduação Psiquiátrica/normas , Psicometria/normas , Smartphone , Mídias Sociais , Estudantes , Jogos de Vídeo , Adolescente , Adulto , Comportamento Aditivo/epidemiologia , Hong Kong/epidemiologia , Humanos , Internet/estatística & dados numéricos , Psicometria/instrumentação , Smartphone/estatística & dados numéricos , Mídias Sociais/estatística & dados numéricos , Estudantes/estatística & dados numéricos , Universidades/estatística & dados numéricos , Jogos de Vídeo/estatística & dados numéricos , Adulto Jovem
14.
Bioinformatics ; 33(6): 893-900, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-27998937

RESUMO

Motivation: Incorporating experimental data into constraint-based models can improve the quality and accuracy of their metabolic flux predictions. Unfortunately, routinely and easily measured experimental data such as growth rates, extracellular fluxes, transcriptomics and even proteomics are not always sufficient to significantly improve metabolic flux predictions. Results: We developed a new method (called REPPS) for incorporating experimental measurements of growth rates and extracellular fluxes from a set of perturbed reference strains (RSs) and a parental strain (PS) to substantially improve the predicted flux distribution of the parental strain. Using data from five single gene knockouts and the wild type strain, we decrease the mean squared error of predicted central metabolic fluxes by ∼47% compared to parsimonious flux balance analysis (pFBA). This decrease in error further improves flux predictions for new knockout strains. Furthermore, REPPS is less sensitive to the completeness of the metabolic network than pFBA. Availability and Implementation: Code is available in the Supplementary data available at Bioinformatics online. Contact: reed@engr.wisc.edu. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Redes e Vias Metabólicas , Modelos Biológicos , Software , Biologia de Sistemas/métodos , Escherichia coli/genética , Escherichia coli/metabolismo , Técnicas de Inativação de Genes
15.
Am J Pathol ; 187(6): 1288-1300, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28399390

RESUMO

Chronic obstructive pulmonary disease (COPD) comprises chronic bronchitis and emphysema, and is a leading cause of morbidity and mortality. Because tissue destruction is the prominent characteristic of emphysema, extracellular proteinases, particularly those with elastolytic ability, are often considered to be key drivers in this disease. Several human and mouse studies have implicated roles for matrix metalloproteinases (MMPs), particularly macrophage-derived proteinases, in COPD pathogenesis. MMP-28 is expressed by the pulmonary epithelium and macrophage, and we have found that it regulates macrophage recruitment and polarization. We hypothesized that MMP-28 has contributory roles in emphysema via alteration of macrophage numbers and activation. Because of the established association of emphysema pathogenesis to macrophage influx, we evaluated the inflammatory changes and lung histology of Mmp28-/- mice exposed to 3 and 6 months of cigarette smoke. At earlier time points, we found altered macrophage polarization in the smoke-exposed Mmp28-/- lung consistent with other published findings that MMP-28 regulates macrophage activation. At both 3 and 6 months, Mmp28-/- mice had blunted inflammatory responses more closely resembling nonsmoked mice, with a reduction in neutrophil recruitment and CXCL1 chemokine expression. By 6 months, Mmp28-/- mice were protected from emphysema. These results highlight a previously unrecognized role for MMP-28 in promoting chronic lung inflammation and tissue remodeling induced by cigarette smoke and highlight another potential target to modulate COPD.


Assuntos
Metaloproteinases da Matriz Secretadas/fisiologia , Enfisema Pulmonar/enzimologia , Animais , Líquido da Lavagem Broncoalveolar/citologia , Quimiocinas/metabolismo , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Enzimológica da Expressão Gênica/fisiologia , Pulmão/enzimologia , Macrófagos Alveolares/enzimologia , Masculino , Metaloproteinases da Matriz Secretadas/deficiência , Metaloproteinases da Matriz Secretadas/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos/fisiologia , Pneumonia/enzimologia , Pneumonia/etiologia , Pneumonia/genética , Pneumonia/patologia , Doença Pulmonar Obstrutiva Crônica/enzimologia , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologia , Poluição por Fumaça de Tabaco/efeitos adversos
16.
Biotechnol Bioeng ; 115(9): 2328-2340, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29940066

RESUMO

Recent progress in metabolic engineering and synthetic biology enables the use of microorganisms for the production of chemicals-"bio-based chemicals." However, it is still unclear which chemicals have the highest economic prospect. To this end, we develop a framework for the identification of such promising ones. Specifically, we first develop a genome-scale constraint-based metabolic modeling approach, which is used to identify a candidate pool of 209 chemicals (together with the estimated yield, productivity, and residence time for each) from the intersection of the high-production-volume chemicals and the KEGG and MetaCyc databases. Second, we design three screening criteria based on a chemical's profit margin, market volume, and market size. The total process cost, including the downstream separation cost, is systematically incorporated into the evaluation. Third, given the three aforementioned criteria, we identify 32 products as economically promising if the maximum yields can be achieved, and 22 products if the maximum productivities can be achieved. The breakeven titer that renders zero profit margin for each product is also presented. Comparisons between extracellular and intracellular production, as well as Escherichia coli and Saccharomyces cerevisiae systems are also discussed. The proposed framework provides important guidance for future studies in the production of bio-based chemicals. It is also flexible in that the databases, yield estimations, and criteria can be modified to customize the screening.


Assuntos
Produtos Biológicos/metabolismo , Biotecnologia/métodos , Engenharia Metabólica/métodos , Biologia Sintética/métodos , Produtos Biológicos/economia , Biotecnologia/economia , Biologia Computacional/métodos , Custos e Análise de Custo , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Fermentação , Engenharia Metabólica/economia , Redes e Vias Metabólicas/genética , Metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo
17.
Ecol Appl ; 28(3): 749-760, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29509310

RESUMO

The biodiversity and high productivity of coastal terrestrial and aquatic habitats are the foundation for important benefits to human societies around the world. These globally distributed habitats need frequent and broad systematic assessments, but field surveys only cover a small fraction of these areas. Satellite-based sensors can repeatedly record the visible and near-infrared reflectance spectra that contain the absorption, scattering, and fluorescence signatures of functional phytoplankton groups, colored dissolved matter, and particulate matter near the surface ocean, and of biologically structured habitats (floating and emergent vegetation, benthic habitats like coral, seagrass, and algae). These measures can be incorporated into Essential Biodiversity Variables (EBVs), including the distribution, abundance, and traits of groups of species populations, and used to evaluate habitat fragmentation. However, current and planned satellites are not designed to observe the EBVs that change rapidly with extreme tides, salinity, temperatures, storms, pollution, or physical habitat destruction over scales relevant to human activity. Making these observations requires a new generation of satellite sensors able to sample with these combined characteristics: (1) spatial resolution on the order of 30 to 100-m pixels or smaller; (2) spectral resolution on the order of 5 nm in the visible and 10 nm in the short-wave infrared spectrum (or at least two or more bands at 1,030, 1,240, 1,630, 2,125, and/or 2,260 nm) for atmospheric correction and aquatic and vegetation assessments; (3) radiometric quality with signal to noise ratios (SNR) above 800 (relative to signal levels typical of the open ocean), 14-bit digitization, absolute radiometric calibration <2%, relative calibration of 0.2%, polarization sensitivity <1%, high radiometric stability and linearity, and operations designed to minimize sunglint; and (4) temporal resolution of hours to days. We refer to these combined specifications as H4 imaging. Enabling H4 imaging is vital for the conservation and management of global biodiversity and ecosystem services, including food provisioning and water security. An agile satellite in a 3-d repeat low-Earth orbit could sample 30-km swath images of several hundred coastal habitats daily. Nine H4 satellites would provide weekly coverage of global coastal zones. Such satellite constellations are now feasible and are used in various applications.


Assuntos
Biodiversidade , Tecnologia de Sensoriamento Remoto/instrumentação , Oceanos e Mares , Fitoplâncton
18.
Mol Ther ; 24(4): 779-87, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26732878

RESUMO

Inhibition of vascular smooth muscle cell (VSMC) proliferation by drug eluting stents has markedly reduced intimal hyperplasia and subsequent in-stent restenosis. However, the effects of antiproliferative drugs on endothelial cells (EC) contribute to delayed re-endothelialization and late stent thrombosis. Cell-targeted therapies to inhibit VSMC remodeling while maintaining EC health are necessary to allow vascular healing while preventing restenosis. We describe an RNA aptamer (Apt 14) that functions as a smart drug by preferentially targeting VSMCs as compared to ECs and other myocytes. Furthermore, Apt 14 inhibits phosphatidylinositol 3-kinase/protein kinase-B (PI3K/Akt) and VSMC migration in response to multiple agonists by a mechanism that involves inhibition of platelet-derived growth factor receptor (PDGFR)-ß phosphorylation. In a murine model of carotid injury, treatment of vessels with Apt 14 reduces neointimal formation to levels similar to those observed with paclitaxel. Importantly, we confirm that Apt 14 cross-reacts with rodent and human VSMCs, exhibits a half-life of ~300 hours in human serum, and does not elicit immune activation of human peripheral blood mononuclear cells. We describe a VSMC-targeted RNA aptamer that blocks cell migration and inhibits intimal formation. These findings provide the foundation for the translation of cell-targeted RNA therapeutics to vascular disease.


Assuntos
Aptâmeros de Nucleotídeos/farmacologia , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Neointima/terapia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Meia-Vida , Humanos , Camundongos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/citologia , Neointima/metabolismo , Fosforilação , Ratos
19.
Sex Abuse ; 29(6): 563-591, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26556784

RESUMO

Transcripts of chat logs of naturally occurring, sexually exploitative interactions between offenders and victims that took place via Internet communication platforms were analyzed. The aim of the study was to examine the modus operandi of offenders in such interactions, with particular focus on the specific strategies they use to engage victims, including discursive tactics. We also aimed to ascertain offenders' underlying motivation and function of engagement in online interactions with children. Five cases, comprising 29 transcripts, were analyzed using qualitative thematic analysis with a discursive focus. In addition to this, police reports were reviewed for descriptive and case-specific information. Offenders were men aged between 27 and 52 years ( M = 33.6, SD = 5.6), and the number of children they communicated with ranged from one to 12 ( M = 4.6, SD = 4.5). Victims were aged between 11 and 15 ( M = 13.00, SD = 1.2), and were both female and male. Three offenders committed online sexual offenses, and two offenders committed contact sexual offenses in addition to online sexual offenses. The analysis of transcripts revealed that interactions between offenders and victims were of a highly sexual nature, and that offenders used a range of manipulative strategies to engage victims and achieve their compliance. It appeared that offenders engaged in such interactions for the purpose of sexual arousal and gratification, as well as fantasy fulfillment.


Assuntos
Abuso Sexual na Infância/psicologia , Criminosos/psicologia , Internet , Pedofilia/psicologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Comportamento Sexual/psicologia
20.
Glob Chang Biol ; 22(1): 121-36, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26015089

RESUMO

Organic matter (OM) plays a major role in both terrestrial and oceanic biogeochemical cycles. The amount of carbon stored in these systems is far greater than that of carbon dioxide (CO2 ) in the atmosphere, and annual fluxes of CO2 from these pools to the atmosphere exceed those from fossil fuel combustion. Understanding the processes that determine the fate of detrital material is important for predicting the effects that climate change will have on feedbacks to the global carbon cycle. However, Earth System Models (ESMs) typically utilize very simple formulations of processes affecting the mineralization and storage of detrital OM. Recent changes in our view of the nature of this material and the factors controlling its transformation have yet to find their way into models. In this review, we highlight the current understanding of the role and cycling of detrital OM in terrestrial and marine systems and examine how this pool of material is represented in ESMs. We include a discussion of the different mineralization pathways available as organic matter moves from soils, through inland waters to coastal systems and ultimately into open ocean environments. We argue that there is strong commonality between aspects of OM transformation in both terrestrial and marine systems and that our respective scientific communities would benefit from closer collaboration.


Assuntos
Ciclo do Carbono , Modelos Teóricos , Oceanos e Mares , Carbono/metabolismo , Ecossistema , Solo/química
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