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1.
Sci Total Environ ; 944: 173819, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-38857807

RESUMEN

Optimizing crop distribution stands as a pivotal approach to climate change adaption, enhancing crop production sustainability, and has been recognized for its immense potential in ensuring food security while minimizing environmental impacts. Here, we developed a climate-adaptive framework to optimize the distribution of staple crops (i.e., wheat, maize, and rice) to meet the multi-dimensional needs of crop production in China. The framework considers the feasibility of the multiple cropping systems (harvesting more than once on a cropland a year) and adopts a multi-dimensional approach, incorporating goals related to crop production, water consumption, and greenhouse gas (GHG) emissions. By optimizing, the total irrigated area of three crops would decrease by 7.7 % accompanied by a substantial 69.8 % increase in rain-fed areas compared to the baseline in 2010. This optimized strategy resulted in a notable 10.0 % reduction in total GHG emissions and a 13.1 % decrease in irrigation water consumption while maintaining consistent crop production levels. In 2030, maintaining the existing crop distribution and relying solely on yield growth would lead to a significant maize production shortfall of 27.0 %, highlighting a looming challenge. To address this concern, strategic adjustments were made by reducing irrigated areas for wheat, rice, and maize by 2.3 %, 12.8 %, and 6.1 %, respectively, while simultaneously augmenting rain-fed areas for wheat and maize by 120.2 % and 55.9 %, respectively. These modifications ensure that production demands for all three crops are met, while yielding a 6.9 % reduction in GHG emissions and a 15.1 % reduction in irrigation water consumption. This optimization strategy offers a promising solution to alleviate severe water scarcity issues and secure a sustainable agricultural future, effectively adapting to evolving crop production demands in China.


Asunto(s)
Cambio Climático , Productos Agrícolas , Gases de Efecto Invernadero , Gases de Efecto Invernadero/análisis , China , Productos Agrícolas/crecimiento & desarrollo , Agricultura/métodos , Abastecimiento de Alimentos/métodos , Abastecimiento de Agua , Zea mays/crecimiento & desarrollo , Triticum/crecimiento & desarrollo , Producción de Cultivos/métodos
2.
Environ Sci Technol ; 57(39): 14539-14547, 2023 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-37729112

RESUMEN

Increased interest in greenhouse gas (GHG) emissions, including recent legislative action and voluntary programs, has increased attention on quantifying and ultimately reducing methane emissions from the natural gas supply chain. While inventories used for public or corporate GHG policies have traditionally utilized bottom-up (BU) methods to estimate emissions, the validity of such inventories has been questioned. Therefore, there is attention on utilizing full-facility measurements using airborne, satellite, or drone (top-down (TD)) techniques to inform, improve, or validate inventories. This study utilized full-facility estimates from two independent TD methods at 15 midstream natural gas facilities in the U.S.A., which were compared with a contemporaneous daily inventory assembled by the facility operator, employing comprehensive inventory methods. Estimates from the two TD methods statistically agreed in 2 of 28 paired measurements. Operator inventories, which included extensions to capture sources beyond regular inventory requirements and integration of local measurements, estimated significantly lower emissions than the TD estimates for 40 of 43 paired comparisons. Significant disagreement was observed at most facilities, both between the two TD methods and between the TD estimates and operator inventory. These findings have two implications. First, improving inventory estimates will require additional on-site or ground-based diagnostic screening and measurement of all sources. Second, the TD full-facility measurement methods need to undergo further testing, characterization, and potential improvement specifically tailored for complex midstream facilities.

3.
Plants (Basel) ; 12(15)2023 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-37571012

RESUMEN

The remarkable yield performance of super hybrid rice has played a crucial role in ensuring global food security. However, there is a scarcity of studies investigating the contribution of radiation use efficiency (RUE) to hybrid rice yields under different nitrogen and potassium treatments. In this three-year field experiment, we aimed to evaluate the impact of two hybrid rice varieties (Y-liangyou 900: YLY900 and Quanyouhuazhan: QYHZ) under varying nitrogen regimes (N90: 90 kg N ha-1, N120: 120 kg N ha-1, N180: 180 kg N ha-1) and potassium regimes (K120: 120 kg K2O ha-1, K160: 160 kg K2O ha-1, K210: 210 kg K2O ha-1) on grain yield and its physiological determinants, including RUE, intercepted photosynthetically active radiation (IPAR), aboveground biomass production, and harvest index (HI). Our results revealed that both rice varieties exhibited significantly higher yields when coupled with nitrogen and potassium fertilization. Compared to the N90 × K120 treatment, the N120 × K160 and N180 × K210 combinations resulted in substantial increases in grain yield (12.0% and 21.1%, respectively) and RUE (11.9% and 21.4%, respectively). The YLY900 variety showed notable yield improvement due to enhanced aboveground biomass production resulting from increased IPAR and RUE. In contrast, the QYHZ variety's aboveground biomass accumulation was primarily influenced by RUE rather than IPAR, resulting in higher RUE and grain yields of 9.2% and 5.3%, respectively, compared to YLY900. Importantly, fertilization led to significant increases in yield, biomass, and RUE, while HI remained relatively constant. Both varieties demonstrated a positive relationship between grain yield and IPAR and RUE. Multiple regression analysis indicated that increasing RUE was the primary driver of yield improvement in hybrid rice varieties. By promoting sustainable agriculture and enhancing fertilizer management, elevating nitrogen and potassium levels from a low base would synergistically enhance rice yield and RUE, emphasizing the critical importance of RUE in hybrid rice productivity compared to HI.

4.
Genes (Basel) ; 14(6)2023 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-37372377

RESUMEN

Limiting harm to organisms caused by genetic sampling is an important consideration for rare species, and a number of non-destructive sampling techniques have been developed to address this issue in freshwater mussels. Two methods, visceral swabbing and tissue biopsies, have proven to be effective for DNA sampling, though it is unclear as to which method is preferable for genotyping-by-sequencing (GBS). Tissue biopsies may cause undue stress and damage to organisms, while visceral swabbing potentially reduces the chance of such harm. Our study compared the efficacy of these two DNA sampling methods for generating GBS data for the unionid freshwater mussel, the Texas pigtoe (Fusconaia askewi). Our results find both methods generate quality sequence data, though some considerations are in order. Tissue biopsies produced significantly higher DNA concentrations and larger numbers of reads when compared with swabs, though there was no significant association between starting DNA concentration and number of reads generated. Swabbing produced greater sequence depth (more reads per sequence), while tissue biopsies revealed greater coverage across the genome (at lower sequence depth). Patterns of genomic variation as characterized in principal component analyses were similar regardless of the sampling method, suggesting that the less invasive swabbing is a viable option for producing quality GBS data in these organisms.


Asunto(s)
Bivalvos , Unionidae , Animales , Genotipo , Técnicas de Genotipaje/métodos , Biopsia , ADN/genética , Bivalvos/genética , Unionidae/genética
5.
Sci Rep ; 13(1): 720, 2023 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-36639680

RESUMEN

Water deficit stress exposure frequently constrains plant and agri-food production globally. Biostimulants (BSs) can be considered a new tool in mitigating water deficit stress. This study aimed to understand how BSs influence water deficit stress perceived by savory plants (Satureja hortensis L.), an important herb used for nutritional and herbal purposes in the Middle East. Three BS treatments, including bio-fertilizers, humic acid and foliar application of amino acid (AA), were implemented. Each treatment was applied to savory plants using three irrigation regimes (low, moderate and severe water deficit stress FC100, FC75 and FC50, respectively). Foliar application of AA increased dry matter yield, essential oil (EO) content and EO yield by 22%, 31% and 57%, respectively. The greatest EO yields resulted from the moderate (FC75) and severe water deficit stress (FC50) treatments treated with AA. Primary EO constituents included carvacrol (39-43%), gamma-terpinene (27-37%), alpha-terpinene (4-7%) and p-cymene (2-5%). Foliar application of AA enhanced carvacrol, gamma-terpinene, alpha-terpinene and p-cymene content by 6%, 19%, 46% and 18%, respectively. Physiological characteristics were increased with increasing water shortage and application of AA. Moreover, the maximum activities of superoxide dismutase (3.17 unit mg-1 min-1), peroxidase (2.60 unit mg-1 min-1) and catalase (3.08 unit mg-1 min-1) were obtained from plants subjected to severe water deficit stress (FC50) and treated with AA. We conclude that foliar application of AA under water deficit stress conditions would improve EO quantity and quality in savory.


Asunto(s)
Aceites Volátiles , Satureja , Aceites Volátiles/farmacología , Aceites Volátiles/química , Deshidratación , Satureja/química , Agua
6.
Environ Sci Technol ; 56(20): 14743-14752, 2022 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-36201663

RESUMEN

Methane mitigation from the oil and gas (O&G) sector represents a key near-term global climate action opportunity. Recent legislation in the United States requires updating current methane reporting programs for oil and gas facilities with empirical data. While technological advances have led to improvements in methane emissions measurements and monitoring, the overall effectiveness of mitigation strategies rests on quantifying spatially and temporally varying methane emissions more accurately than the current approaches. In this work, we demonstrate a quantification, monitoring, reporting, and verification framework that pairs snapshot measurements with continuous emissions monitoring systems (CEMS) to reconcile measurements with inventory estimates and account for intermittent emission events. We find that site-level emissions exhibit significant intraday and daily emission variations. Snapshot measurements of methane can span over 3 orders of magnitude and may have limited application in developing annualized inventory estimates at the site level. Consequently, while official inventories underestimate methane emissions on average, emissions at individual facilities can be higher or lower than inventory estimates. Using CEMS, we characterize distributions of frequency and duration of intermittent emission events. Technologies that allow high sampling frequency such as CEMS, paired with a mechanistic understanding of facility-level events, are key to an accurate accounting of short-duration, episodic, and high-volume events that are often missed in snapshot surveys and to scale snapshot measurements to annualized emissions estimates.


Asunto(s)
Contaminantes Atmosféricos , Gas Natural , Contaminantes Atmosféricos/análisis , Metano/análisis , Gas Natural/análisis , Sulfuros , Estados Unidos , United States Environmental Protection Agency
7.
Environ Sci Technol ; 56(13): 9632-9640, 2022 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-35699220

RESUMEN

Mitigating methane emissions is vital in meeting global climate targets, but there is a lack of understanding of emissions and abatement opportunities to enable this. The natural gas supply chain is a key emission source, where methane emissions from liquefied natural gas (LNG) shipping have until now not been directly measured. This study provides the first measurement and modeling of total methane and CO2 emissions from an LNG carrier on a round trip voyage from the USA to Belgium and back, including loading, laden voyage, unloading, and ballast voyage, measuring emissions from exhaust stacks, vents, and fugitives. Venting and fugitive emissions were extremely low, contributing less than 0.1% of total greenhouse gas emissions. CO2 emissions from fuel usage were also lower than previous estimates due to improved efficiencies in modern engines and ship design. However, methane slip through the engines were higher than those in prior studies, averaging 3.8% across all engines: equating to 0.1% of delivered LNG. Generator engines are not typically included in emissions analyses but were the key cause of methane emissions. Engines exhibited higher methane slip rates at low loads, and optimized operation could reduce slip rates by half. More measurement studies are now needed to better understand fleet emissions and enable cost-effective mitigation strategies.


Asunto(s)
Contaminantes Atmosféricos , Gas Natural , Contaminantes Atmosféricos/análisis , Dióxido de Carbono , Metano/análisis , Gas Natural/análisis , Navíos
8.
Sci Total Environ ; 829: 154277, 2022 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-35276157

RESUMEN

In comparing observation based methane emission estimates for oil and gas well sites to routine emissions reported in inventories, the time scale of the measurement should match the time scale over which the inventoried emissions are estimated. Since many measurements are of relatively short duration (seconds to hours), a tool is needed to estimate emissions over these time scales rather than the annual totals reported in most emission inventories. This work presents a tool for estimating routine emissions from oil and gas well sites at multiple time scales; emissions at well sites vary over time due to changes in oil and gas production rates, operating practices and operational modes at the sites. Distributions of routine emissions (expected and inventoried) from well sites are generally skewed, and the nature and degree to which the distributions are skewed depends on the time scales over which emissions are aggregated. Abnormal emissions can create additional skew in these distributions. At very short time scales (emissions aggregated over 1 min) case study distributions presented in this work are both skewed and bimodal, with the modes depending on whether liquid storage tanks are flashing at the time of the measurement and whether abnormal emissions are occurring. At longer time scales (emissions aggregated over 1 day) distributions of routine emissions simulated in this work can have multiple modes if short duration, high emission rate events, such as liquid unloadings or large abnormal emissions, occur at the site. Multiple applications of the methane emission estimation tool (MEET), developed in this work, are presented. These results emphasize the importance of developing detailed emission inventories, which incorporate operational data, when comparing measurements to routine emissions. The model described in this work supports such comparisons and is freely available.


Asunto(s)
Contaminantes Atmosféricos , Yacimiento de Petróleo y Gas , Contaminantes Atmosféricos/análisis , Metano/análisis , Gas Natural/análisis , Factores de Tiempo
9.
J Nutr ; 151(10): 3125-3136, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-34224573

RESUMEN

BACKGROUND: Using indicator amino acid oxidation methodology, the mean dietary requirement of adult dogs for methionine (Met) was estimated to be ∼66% of the current recommended allowance. Dogs fed a diet formulated to provide the estimated mean Met requirement for 32 wk maintained plasma Met, seemingly supported by betaine oxidation. OBJECTIVE: To gain a better understanding of the metabolic changes that were associated with supporting plasma Met when dogs were fed a limited Met diet over 32 wk, we analyzed plasma samples taken from that study using a data-driven metabolomics approach. METHODS: Labrador retrievers (20 females/13 males; mean age: 4.9 y; range: 2.0-7.9 y) were fed semi-purified, nutritionally complete diets. After 4 wk of feeding a control diet (DL-Met; 1.37 g/1000 kcal), 17 dogs remained on this diet and 16 were transitioned to a test diet formulated to the estimated mean Met requirement (0.55 g/1000 kcal), with dietary total sulfur amino acid maintained with additional l-cystine (Cys). Dogs were individually fed diets to maintain a stable body weight at an ideal body condition score for 32 wk. Plasma samples from fasted blood collected at baseline and 8 and 32 wk were analyzed using untargeted metabolic profiling. RESULTS: Analysis of metabolites (n = 593) confirmed our primary findings (increased Met, betaine, and dimethylglycine). Metabolite changes consistent with repartitioning choline to support Met cycling included reduced pools of lipids derived via phosphatidylethanolamine N-methyltransferase and enhanced fatty acid oxidation. Some changes were consistent with metabolomics studies reported in other species that used interventions known to extend life span (caloric- and Met-restricted diets or feeding strategy). CONCLUSIONS: Changes in the plasma metabolome were consistent with reported adaptations to support Met-dependent activities. We propose that feeding a limited-Met, high-Cys diet using the estimated mean Met requirement in adult Labrador retrievers alters regulation of the Met cycle, thereby altering metabolism, similar to interventions that extend life span.


Asunto(s)
Cistina , Metionina , Alimentación Animal/análisis , Animales , Dieta/veterinaria , Perros , Femenino , Longevidad , Masculino , Metaboloma , Metionina/metabolismo
10.
Metabolomics ; 17(2): 14, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462674

RESUMEN

INTRODUCTION: The Endosialin/CD248/TEM1 protein is expressed in adipose tissue and its expression increases with obesity. Recently, genetic deletion of CD248 has been shown to protect mice against atherosclerosis on a high fat diet. OBJECTIVES: We investigated the effect of high fat diet feeding on visceral fat pads and circulating lipid profiles in CD248 knockout mice compared to controls. METHODS: From 10 weeks old, CD248-/- and +/+ mice were fed either chow (normal) diet or a high fat diet for 13 weeks. After 13 weeks the metabolic profiles and relative quantities of circulating lipid species were assessed using ultra high performance liquid chromatography-quadrupole time-of flight mass spectrometry (UHPLC-MS) with high resolution accurate mass (HRAM) capability. RESULTS: We demonstrate a specific reduction in the size of the perirenal fat pad in CD248-/- mice compared to CD248+/+, despite similar food intake. More strikingly, we identify significant, diet-dependent differences in the serum metabolic phenotypes of CD248 null compared to age and sex-matched wildtype control mice. Generalised protection from HFD-induced lipid accumulation was observed in CD248 null mice compared to wildtype, with particular reduction noted in the lysophosphatidylcholines, phosphatidylcholines, cholesterol and carnitine. CONCLUSIONS: Overall these results show a clear and protective metabolic consequence of CD248 deletion in mice, implicating CD248 in lipid metabolism or trafficking and opening new avenues for further investigation using anti-CD248 targeting agents.


Asunto(s)
Antígenos CD/genética , Antígenos CD/metabolismo , Cromatografía Liquida , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Espectrometría de Masas en Tándem , Tejido Adiposo/metabolismo , Animales , Antígenos de Neoplasias , Carnitina/metabolismo , Colesterol , Cromatografía Líquida de Alta Presión , Dieta Alta en Grasa , Femenino , Grasa Intraabdominal/metabolismo , Hígado/metabolismo , Masculino , Ratones , Ratones Noqueados , Obesidad/metabolismo , Fosfatidilcolinas/metabolismo , Transcriptoma
12.
Br J Nutr ; 123(12): 1333-1344, 2020 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-32100649

RESUMEN

Methionine, an essential sulphur-containing amino acid (SAA), plays an integral role in many metabolic processes. Evidence for the methionine requirements of adult dogs is limited, and we employed the indicator amino acid oxidation (IAAO) method to estimate dietary methionine requirements in Labrador retrievers (n 21). Using semi-purified diets, the mean requirement was 0·55 (95 % CI 0·41, 0·71) g/4184 kJ. In a subsequent parallel design study, three groups of adult Labrador retrievers (n 52) were fed semi-purified diets with 0·55 g/4184 kJ (test diet 1), 0·71 g/4184 kJ (test diet 2) or 1·37 g/4184 kJ (control diet) of methionine for 32 weeks to assess the long-term consequences of feeding. The total SAA content (2·68 g/4184 kJ) was maintained through dietary supplementation of cystine. Plasma methionine did not decrease in test group and increased significantly on test diet 1 in weeks 8 and 16 compared with control. Reducing dietary methionine did not have a significant effect on whole blood, plasma or urinary taurine or plasma N-terminal pro B-type natriuretic peptide. Significant effects in both test diets were observed for cholesterol, betaine and dimethylglycine. In conclusion, feeding methionine at the IAAO-estimated mean was sufficient to maintain plasma methionine over 32 weeks when total SAA was maintained. However, choline oxidation may have increased to support plasma methionine and have additional consequences for lipid metabolism. While the IAAO can be employed to assess essential amino acid requirements, such as methionine in the dog using semi-purified diets, further work is required to establish safe levels for commercial diet formats.


Asunto(s)
Dieta/veterinaria , Suplementos Dietéticos , Perros/metabolismo , Metionina/metabolismo , Necesidades Nutricionales , Aminoácidos/metabolismo , Animales , Oxidación-Reducción
13.
Case Rep Oncol Med ; 2018: 5719382, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30123594

RESUMEN

A 39-year-old male presented with a painful paraspinal mass, which had been present for several weeks. The mass had previously been treated with oral sulfamethoxazole and trimethoprim DS, as the patient reported a history of "boils," with no improvement in his pain or size of the mass. No further diagnostic workup was pursued until he was admitted with intractable pain. Eventual biopsy revealed adenocarcinoma, likely of pulmonary origin. This report, as well as other incoming cases, highlights this rare phenomenon of muscular metastases as the sole presentation of a distant primary malignancy.

14.
J Cell Mol Med ; 22(9): 4317-4327, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-29974666

RESUMEN

The Src family kinases (SFK) are a group of signalling molecules with important regulatory functions in inflammation and haemostasis. Leucocytes and platelets express multiple isoforms of the SFKs. Previous studies used broad-spectrum pharmacological inhibitors, or murine models deficient in multiple SFK isoforms, to demonstrate the functional consequences of deficiencies in SFK signalling. Here, we hypothesized that individual SFK operate in a non-redundant fashion in the thrombo-inflammatory recruitment of monocyte during atherosclerosis. Using in vitro adhesion assays and single SFK knockout mice crossed with the ApoE-/- model of atherosclerosis, we find that SFK signalling regulates platelet-dependent recruitment of monocytes. However, loss of a single SFK, Fgr or Lyn, reduced platelet-mediated monocyte recruitment in vitro. This translated into a significant reduction in the burden of atherosclerotic disease in Fgr-/- /ApoE-/- or Lyn-/- /ApoE-/- animals. SFK signalling is not redundant in thrombo-inflammatory vascular disease and individual SFK may represent targets for therapeutic intervention.


Asunto(s)
Apolipoproteínas E/genética , Enfermedad de la Arteria Coronaria/genética , Monocitos/metabolismo , Proteínas Proto-Oncogénicas/genética , Familia-src Quinasas/genética , Animales , Aorta/metabolismo , Aorta/patología , Apolipoproteínas E/deficiencia , Adhesión Celular , Enfermedad de la Arteria Coronaria/etiología , Enfermedad de la Arteria Coronaria/metabolismo , Enfermedad de la Arteria Coronaria/patología , Dieta Alta en Grasa/efectos adversos , Femenino , Regulación de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos/patología , Cultivo Primario de Células , Proteínas Proto-Oncogénicas/deficiencia , Transducción de Señal , Familia-src Quinasas/deficiencia
15.
J Am Stat Assoc ; 113(521): 340-356, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29983475

RESUMEN

A natural Bayesian approach for mixture models with an unknown number of components is to take the usual finite mixture model with symmetric Dirichlet weights, and put a prior on the number of components-that is, to use a mixture of finite mixtures (MFM). The most commonly-used method of inference for MFMs is reversible jump Markov chain Monte Carlo, but it can be nontrivial to design good reversible jump moves, especially in high-dimensional spaces. Meanwhile, there are samplers for Dirichlet process mixture (DPM) models that are relatively simple and are easily adapted to new applications. It turns out that, in fact, many of the essential properties of DPMs are also exhibited by MFMs-an exchangeable partition distribution, restaurant process, random measure representation, and stick-breaking representation-and crucially, the MFM analogues are simple enough that they can be used much like the corresponding DPM properties. Consequently, many of the powerful methods developed for inference in DPMs can be directly applied to MFMs as well; this simplifies the implementation of MFMs and can substantially improve mixing. We illustrate with real and simulated data, including high-dimensional gene expression data used to discriminate cancer subtypes.

16.
J Immunol ; 198(7): 2834-2843, 2017 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-28193827

RESUMEN

Two major monocyte subsets, CD14+CD16- (classical) and CD14+/dimCD16+ (nonclassical/intermediate), have been described. Each has different functions ascribed in its interactions with vascular endothelial cells (EC), including migration and promoting inflammation. Although monocyte subpopulations have been studied in isolated systems, their influence on EC and on the course of inflammation has been ignored. In this study, using unstimulated or cytokine-activated EC, we observed significant differences in the recruitment, migration, and reverse migration of human monocyte subsets. Associated with this, and based on their patterns of cytokine secretion, there was a difference in their capacity to activate EC and support the secondary recruitment of flowing neutrophils. High levels of TNF were detected in cocultures with nonclassical/intermediate monocytes, the blockade of which significantly reduced neutrophil recruitment. In contrast, classical monocytes secreted high levels of IL-6, the blockade of which resulted in increased neutrophil recruitment. When cocultures contained both monocyte subsets, or when conditioned supernatant from classical monocytes cocultures (IL-6hi) was added to nonclassical/intermediate monocyte cocultures (TNFhi), the activating effects of TNF were dramatically reduced, implying that when present, the anti-inflammatory activities of IL-6 were dominant over the proinflammatory activities of TNF. These changes in neutrophil recruitment could be explained by regulation of E-selectin on the cocultured EC. This study suggests that recruited human monocyte subsets trigger a regulatory pathway of cytokine-mediated signaling at the EC interface, and we propose that this is a mechanism for limiting the phlogistic activity of newly recruited monocytes.


Asunto(s)
Quimiotaxis de Leucocito/inmunología , Células Endoteliales/inmunología , Inflamación/inmunología , Monocitos/inmunología , Transducción de Señal/inmunología , Separación Celular , Citometría de Flujo , Humanos , Interleucina-6/inmunología , Reacción en Cadena de la Polimerasa , Factor de Necrosis Tumoral alfa/inmunología
17.
PLoS One ; 11(4): e0151832, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27050167

RESUMEN

BACKGROUND: Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. METHODOLOGY/PRINCIPLE FINDINGS: EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). CONCLUSIONS/SIGNIFICANCE: Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR-targeted, doxorubicin-loaded minicells for effective treatment of human patients with recurrent glioblastoma.


Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Modelos Animales de Enfermedad , Doxorrubicina/uso terapéutico , Sistemas de Liberación de Medicamentos , Glioblastoma/tratamiento farmacológico , Terapia Molecular Dirigida , Animales , Antibióticos Antineoplásicos/farmacocinética , Anticuerpos Monoclonales/uso terapéutico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Proliferación Celular/efectos de los fármacos , Perros , Doxorrubicina/farmacocinética , Receptores ErbB , Femenino , Glioblastoma/mortalidad , Glioblastoma/patología , Humanos , Masculino , Estadificación de Neoplasias , Tasa de Supervivencia , Distribución Tisular , Células Tumorales Cultivadas
18.
Environ Sci Technol ; 49(8): 5161-9, 2015 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-25826444

RESUMEN

Fugitive losses from natural gas distribution systems are a significant source of anthropogenic methane. Here, we report on a national sampling program to measure methane emissions from 13 urban distribution systems across the U.S. Emission factors were derived from direct measurements at 230 underground pipeline leaks and 229 metering and regulating facilities using stratified random sampling. When these new emission factors are combined with estimates for customer meters, maintenance, and upsets, and current pipeline miles and numbers of facilities, the total estimate is 393 Gg/yr with a 95% upper confidence limit of 854 Gg/yr (0.10% to 0.22% of the methane delivered nationwide). This fraction includes emissions from city gates to the customer meter, but does not include other urban sources or those downstream of customer meters. The upper confidence limit accounts for the skewed distribution of measurements, where a few large emitters accounted for most of the emissions. This emission estimate is 36% to 70% less than the 2011 EPA inventory, (based largely on 1990s emission data), and reflects significant upgrades at metering and regulating stations, improvements in leak detection and maintenance activities, as well as potential effects from differences in methodologies between the two studies.


Asunto(s)
Monitoreo del Ambiente/métodos , Metano/análisis , Gas Natural , Contaminantes Atmosféricos/análisis , Gas Natural/análisis , Estados Unidos
19.
Nat Med ; 21(5): 467-475, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25894827

RESUMEN

During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3 zeta delta (14.3.3.ζδ) protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin-induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type 1 diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to that of healthy age-matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Control of patient T cell trafficking is re-established by treatment with exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic ischemia-reperfusion injury, Salmonella infection, uveitis and Sjögren's syndrome, PEPITEM reduced T cell recruitment into inflamed tissues.


Asunto(s)
Autoinmunidad/inmunología , Linfocitos B/citología , Regulación de la Expresión Génica , Homeostasis , Inflamación/inmunología , Linfocitos T/citología , Proteínas 14-3-3/metabolismo , Adiponectina/metabolismo , Adulto , Factores de Edad , Anciano , Envejecimiento , Animales , Artritis Reumatoide/sangre , Cadherinas/metabolismo , Adhesión Celular , Movimiento Celular , Diabetes Mellitus Tipo 1/sangre , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Lisofosfolípidos/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Péptidos/química , Receptores de Adiponectina/metabolismo , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Adulto Joven
20.
Environ Sci Technol ; 49(1): 633-40, 2015 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-25488196

RESUMEN

Emissions from 377 gas actuated (pneumatic) controllers were measured at natural gas production sites and a small number of oil production sites, throughout the United States. A small subset of the devices (19%), with whole gas emission rates in excess of 6 standard cubic feet per hour (scf/h), accounted for 95% of emissions. More than half of the controllers recorded emissions of 0.001 scf/h or less during 15 min of measurement. Pneumatic controllers in level control applications on separators and in compressor applications had higher emission rates than controllers in other types of applications. Regional differences in emissions were observed, with the lowest emissions measured in the Rocky Mountains and the highest emissions in the Gulf Coast. Average methane emissions per controller reported in this work are 17% higher than the average emissions per controller in the 2012 EPA greenhouse gas national emission inventory (2012 GHG NEI, released in 2014); the average of 2.7 controllers per well observed in this work is higher than the 1.0 controllers per well reported in the 2012 GHG NEI.


Asunto(s)
Contaminantes Atmosféricos/análisis , Equipos y Suministros , Metano/análisis , Gas Natural/análisis , Yacimiento de Petróleo y Gas , Estados Unidos
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