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1.
Glob Change Biol Bioenergy ; 16(1): e13114, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38711671

RESUMO

Perennial bioenergy crops are a key tool in decarbonizing global energy systems, but to ensure the efficient use of land resources, it is essential that yields and crop longevity are maximized. Remedial shallow surface tillage is being explored in commercial Miscanthus plantations as an approach to reinvigorate older crops and to rectify poor establishment, improving yields. There are posited links, however, between tillage and losses in soil carbon (C) via increased ecosystem C fluxes to the atmosphere. As Miscanthus is utilized as an energy crop, changes in field C fluxes need to be assessed as part of the C balance of the crop. Here, for the first time, we quantify the C impacts of remedial tillage at a mature commercial Miscanthus plantation in Lincolnshire, United Kingdom. Net ecosystem C production based on eddy covariance flux observations and exported yield totalled 12.16 Mg C ha-1 over the 4.6 year period after tillage, showing the site functioned as a net sink for atmospheric carbon dioxide (CO2). There was no indication of negative tillage induced impacts on soil C stocks, with no difference 3 years post tillage in the surface (0-30 cm) or deep (0-70 cm) soil C stocks between the tilled Miscanthus field and an adjacent paired untilled Miscanthus field. Comparison to historic samples showed surface soil C stocks increased by 11.16 ± 3.91 Mg C ha-1 between pre (October 2011) and post tillage sampling (November 2016). Within the period of the study, however, the tillage did not result in the increased yields necessary to "pay back" the tillage induced yield loss. Rather the crop was effectively re-established, with progressive yield increases over the study period, mirroring expectations of newly planted sites. The overall impacts of remedial tillage will depend therefore, on the longer-term impacts on crop longevity and yields.

2.
Nat Commun ; 15(1): 1987, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443336

RESUMO

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase inhibitor stiripentol emerges as the top hit. Combined profiling and functional studies demonstrate that lactate dehydrogenase A (LDHA)-directed extracellular signal-regulated kinase (ERK) pathway activates yes-associated protein 1 (YAP1)/ signal transducer and activator of transcription 3 (STAT3) transcriptional co-activators in glioblastoma cells to upregulate C-C motif chemokine ligand 2 (CCL2) and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.


Assuntos
Glioblastoma , Animais , Humanos , Camundongos , Glioblastoma/genética , L-Lactato Desidrogenase/genética , Lactato Desidrogenase 5 , Ácido Láctico , Simbiose , Microambiente Tumoral
3.
Leukemia ; 38(3): 521-529, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38245602

RESUMO

Constitutional trisomy 21 (T21) is a state of aneuploidy associated with high incidence of childhood acute myeloid leukemia (AML). T21-associated AML is preceded by transient abnormal myelopoiesis (TAM), which is triggered by truncating mutations in GATA1 generating a short GATA1 isoform (GATA1s). T21-associated AML emerges due to secondary mutations in hematopoietic clones bearing GATA1s. Since aneuploidy generally impairs cellular fitness, the paradoxically elevated risk of myeloid malignancy in T21 is not fully understood. We hypothesized that individuals with T21 bear inherent genome instability in hematopoietic lineages that promotes leukemogenic mutations driving the genesis of TAM and AML. We found that individuals with T21 show increased chromosomal copy number variations (CNVs) compared to euploid individuals, suggesting that genome instability could be underlying predisposition to TAM and AML. Acquisition of GATA1s enforces myeloid skewing and maintenance of the hematopoietic progenitor state independently of T21; however, GATA1s in T21 hematopoietic progenitor cells (HPCs) further augments genome instability. Increased dosage of the chromosome 21 (chr21) gene DYRK1A impairs homology-directed DNA repair as a mechanism of elevated mutagenesis. These results posit a model wherein inherent genome instability in T21 drives myeloid malignancy in concert with GATA1s mutations.


Assuntos
Síndrome de Down , Leucemia Mieloide Aguda , Reação Leucemoide , Transtornos Mieloproliferativos , Humanos , Criança , Síndrome de Down/complicações , Variações do Número de Cópias de DNA , Transtornos Mieloproliferativos/genética , Instabilidade Genômica , Leucemia Mieloide Aguda/patologia , Aneuploidia , Trissomia , Fator de Transcrição GATA1/genética
4.
Res Sq ; 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37886538

RESUMO

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase (LDH) inhibitor stiripentol (an FDA-approved anti-seizure drug for Dravet Syndrome) emerges as the top hit. Combined profiling and functional studies demonstrate that LDHA-directed ERK pathway activates YAP1/STAT3 transcriptional co-activators in glioblastoma cells to upregulate CCL2 and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.

5.
Leukemia ; 37(8): 1698-1708, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37391485

RESUMO

Many inherited bone marrow failure syndromes (IBMFSs) present a high risk of transformation to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). During transformation of IBMFSs, hematopoietic stem and progenitor cells (HSPCs) with poor fitness gain ectopic, dysregulated self-renewal secondary to somatic mutations via undefined mechanisms. Here, in the context of the prototypical IBMFS Fanconi anemia (FA), we performed multiplexed gene editing of mutational hotspots in MDS-associated genes in human induced pluripotent stem cells (iPSCs) followed by hematopoietic differentiation. We observed aberrant self-renewal and impaired differentiation of HSPCs with enrichment of RUNX1 insertions and deletions (indels), generating a model of IBMFS-associated MDS. We observed that compared to the failure state, FA MDS cells show mutant RUNX1-mediated blunting of the G1/S cell cycle checkpoint that is normally activated in FA in response to DNA damage. RUNX1 indels also lead to activation of innate immune signaling, which stabilizes the homologous recombination (HR) effector BRCA1, and this pathway can be targeted to abrogate viability and restore sensitivity to genotoxins in FA MDS. Together, these studies develop a paradigm for modeling clonal evolution in IBMFSs, provide basic understanding of the pathogenesis of MDS, and uncover a therapeutic target in FA-associated MDS.


Assuntos
Anemia de Fanconi , Células-Tronco Pluripotentes Induzidas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Anemia de Fanconi/genética , Anemia de Fanconi/patologia , Anemia de Fanconi/terapia , Síndrome Congênita de Insuficiência da Medula Óssea/complicações , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Células-Tronco Pluripotentes Induzidas/patologia , Síndromes Mielodisplásicas/patologia , Mutação , Leucemia Mieloide Aguda/patologia
6.
Sci Total Environ ; 892: 164229, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37245819

RESUMO

Perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorobutane sulfonic acid (PFBS), 6:2 fluorotelomer sulfonic acid (6:2 FTS), and GenX are tested for diffusion and sorption through thermoplastic polyurethane (TPU) and three ethylene interpolymer alloy (PVC-EIA) liners (EIA1, EIA2, and EIA3) with decreasing ketone ethylene ester (KEE) contents. The tests were conducted at room temperature (23 °C), 35 °C, and 50 °C. The tests show significant diffusion through the TPU as manifested by a decrease in the source concentration and an increase in the receptor concentrations of PFOA and PFOS over time, especially at higher temperatures. On the other hand, the PVC-EIA liners show excellent diffusive resistance to the PFAS compounds especially at 23 °C. At higher temperatures, the diffusion resistance of the PVC-EIA liner with the lowest KEE content, EIA3, was best at 50 °C followed by EIA1 (highest KEE content) and finally EIA2. Sorption tests showed no measurable partitioning of any of the compounds to the liners examined. Based on 535 days of diffusion testing, permeation coefficients are provided for all the compounds considered for the four liners at three temperatures. In addition, the Pg values for PFOA and PFOS are provided for a linear low density polyethylene (LLDPE) and a coextruded LLDPE - ethylene vinyl alcohol (EVOH) geomembrane based on 1246 to 1331 days of testing and are compared to those estimated for EIA1, EIA2, and EIA3.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Poliuretanos
7.
Waste Manag ; 161: 43-51, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36863209

RESUMO

The long-term performance of a geosynthetic clay liner (GCL) above a drainage layer and a geocomposite drain (GCD) are investigated. Full-scale tests are used to: (i) assess the integrity of GCL and GCD in a double composite liner below a defect in the primary geomembrane with ageing, and (ii) establish the head at which there was internal erosion in GCL without a carrier geotextile (GTX) such that the bentonite is in direct contact with the underlying gravel drainage. Six years after contact with simulated landfill leachate at 85 °C through an intentional defect on the geomembrane, the GCL resting on the GCD had failed due to degradation of the GTX between the bentonite and the core of the GCD and subsequent erosion of the bentonite into the core structure of the GCD was observed. In addition to complete degradation of its GTX at some locations, the GCD had also experienced extensive stress cracking and rib rollover. The second test demonstrates that if a suitable gravel drainage layer had been used instead of the GCD, the GTX component of the GCL would not have been required for acceptable long-term performance under normal design conditions and indeed could withstand a head of up to 15 m before problems became evident. The findings serve as a warning landfill designers and regulators that more attention must be paid to the service life of all components of double liner systems used in Municipal Solid Waste (MSW) landfills.


Assuntos
Eliminação de Resíduos , Poluentes Químicos da Água , Resíduos Sólidos , Bentonita , Argila , Instalações de Eliminação de Resíduos , Poluentes Químicos da Água/análise
8.
Psychol Med ; 53(9): 3987-3994, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-35311636

RESUMO

BACKGROUND: Children from low-socioeconomic backgrounds exhibit more behavioural difficulties than those from more affluent families. Influential theoretical models specify family stress and child characteristics as mediating this effect. These accounts, however, have often been based on cross-sectional data or longitudinal analyses that do not capture all potential pathways, and therefore may not provide good policy guidance. METHODS: In a UK representative sample of 2399 children aged 5-15, we tested mediation of the effect of household income on parent and teacher reports of conduct problems (CP) via unhealthy family functioning, poor parental mental health, stressful life events, child physical health and reading ability. We applied cross-lagged longitudinal mediation models which allowed for testing of reciprocal effects whereby the hypothesised mediators were modelled as outcomes as well as predictors of CP. RESULTS: We found the predicted significant longitudinal effect of income on CP, but no evidence that it was mediated by the child and family factors included in the study. Instead, we found significant indirect paths from income to parental mental health, child physical health and stressful life events that were transmitted via child CP. CONCLUSION: The results confirm that income is associated with change in CP but do not support models that suggest this effect is transmitted via unhealthy family functioning, parental mental health, child physical health, stressful life events or reading difficulties. Instead, the results highlight that child CP may be a mediator of social inequalities in family psychosocial functioning.


Assuntos
Renda , Saúde Mental , Criança , Humanos , Adolescente , Estudos Transversais , Fatores Socioeconômicos , Inquéritos e Questionários , Pais/psicologia
9.
J Environ Manage ; 328: 116979, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36502710

RESUMO

To safely contain Per-and Polyfluoroalkyl substances (PFAS) in municipal solid waste landfills and contaminated soil monofills, it is necessary to understand how these substances interact with components of engineered systems designed to contain them. This paper examines the interaction between one of the most critical components of the system: a high-density polyethylene (HDPE) geomembrane. The same geomembrane is immersed in PFAS solution and synthetic municipal solid waste leachate containing PFAS for 2.5 years, and the effects of PFAS on antioxidant depletion time is examined. The geomembrane is incubated in ovens at 85-40 °C to obtain data for Arrhenius predictions at typical landfill temperatures. When exposed to PFAS solution alone, the antioxidant depletion times are smaller than when the same geomembrane is immersed in synthetic municipal solid waste leachate alone. The combination of the two has a synergistic effect which leads to an even greater reduction in antioxidant depletion time for this geomembrane, with results showing a 68% decrease in predicted antioxidant depletion time at a typical landfill temperature of 35 °C when PFAS is present in leachate. This study highlights the need to consider the potential impact of PFAS on the service life of geomembranes used to contain them.


Assuntos
Fluorocarbonos , Eliminação de Resíduos , Poluentes Químicos da Água , Polietileno , Resíduos Sólidos , Eliminação de Resíduos/métodos , Antioxidantes , Instalações de Eliminação de Resíduos , Poluentes Químicos da Água/análise
10.
Cell Rep ; 39(4): 110752, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35476984

RESUMO

High-risk forms of B-acute lymphoblastic leukemia (B-ALL) remain a therapeutic challenge. Leukemia-initiating cells (LICs) self-renew and spark relapse and therefore have been the subject of intensive investigation; however, the properties of LICs in high-risk B-ALL are not well understood. Here, we use single-cell transcriptomics and quantitative xenotransplantation to understand LICs in MLL-rearranged (MLL-r) B-ALL. Compared with reported LIC frequencies in acute myeloid leukemia (AML), engraftable LICs in MLL-r B-ALL are abundant. Although we find that multipotent, self-renewing LICs are enriched among phenotypically undifferentiated B-ALL cells, LICs with the capacity to replenish the leukemic cellular diversity can emerge from more mature fractions. While inhibiting oxidative phosphorylation blunts blast proliferation, this intervention promotes LIC emergence. Conversely, inhibiting hypoxia and glycolysis impairs MLL-r B-ALL LICs, providing a therapeutic benefit in xenotransplantation systems. These findings provide insight into the aggressive nature of MLL-r B-ALL and provide a rationale for therapeutic targeting of hypoxia and glycolysis.


Assuntos
Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Glicólise , Humanos , Hipóxia , Leucemia Mieloide Aguda/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
11.
Cell Rep ; 39(1): 110587, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35385744

RESUMO

Hematopoiesis changes over life to meet the demands of maturation and aging. Here, we find that the definitive hematopoietic stem and progenitor cell (HSPC) compartment is remodeled from gestation into adulthood, a process regulated by the heterochronic Lin28b/let-7 axis. Native fetal and neonatal HSPCs distribute with a pro-lymphoid/erythroid bias with a shift toward myeloid output in adulthood. By mining transcriptomic data comparing juvenile and adult HSPCs and reconstructing coordinately activated gene regulatory networks, we uncover the Polycomb repressor complex 1 (PRC1) component Cbx2 as an effector of Lin28b/let-7's control of hematopoietic maturation. We find that juvenile Cbx2-/- hematopoietic tissues show impairment of B-lymphopoiesis, a precocious adult-like myeloid bias, and that Cbx2/PRC1 regulates developmental timing of expression of key hematopoietic transcription factors. These findings define a mechanism of regulation of HSPC output via chromatin modification as a function of age with potential impact on age-biased pediatric and adult blood disorders.


Assuntos
Hematopoese , Células-Tronco Hematopoéticas , MicroRNAs , Complexo Repressor Polycomb 1 , Proteínas de Ligação a RNA , Adulto , Animais , Criança , Redes Reguladoras de Genes , Hematopoese/genética , Células-Tronco Hematopoéticas/metabolismo , Humanos , Recém-Nascido , Linfopoese , Camundongos , Complexo Repressor Polycomb 1/genética , Complexo Repressor Polycomb 1/metabolismo , Proteínas do Grupo Polycomb/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
12.
Blood Adv ; 4(19): 4679-4692, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33002135

RESUMO

Fanconi anemia (FA) is a disorder of DNA repair that manifests as bone marrow (BM) failure. The lack of accurate murine models of FA has refocused efforts toward differentiation of patient-derived induced pluripotent stem cells (IPSCs) to hematopoietic progenitor cells (HPCs). However, an intact FA DNA repair pathway is required for efficient IPSC derivation, hindering these efforts. To overcome this barrier, we used inducible complementation of FANCA-deficient IPSCs, which permitted robust maintenance of IPSCs. Modulation of FANCA during directed differentiation to HPCs enabled the production of FANCA-deficient human HPCs that recapitulated FA genotoxicity and hematopoietic phenotypes relative to isogenic FANCA-expressing HPCs. FANCA-deficient human HPCs underwent accelerated terminal differentiation driven by activation of p53/p21. We identified growth arrest specific 6 (GAS6) as a novel target of activated p53 in FANCA-deficient HPCs and modulate GAS6 signaling to rescue hematopoiesis in FANCA-deficient cells. This study validates our strategy to derive a sustainable, highly faithful human model of FA, uncovers a mechanism of HPC exhaustion in FA, and advances toward future cell therapy in FA.


Assuntos
Anemia de Fanconi , Células-Tronco Pluripotentes Induzidas , Animais , Diferenciação Celular , Anemia de Fanconi/genética , Proteína do Grupo de Complementação A da Anemia de Fanconi/genética , Humanos , Camundongos , Proteína Supressora de Tumor p53/genética
13.
PLoS One ; 15(9): e0237322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881929

RESUMO

A bite from a La Crosse virus (LACV) infected Aedes mosquito can cause La Crosse encephalitis (LACE), which is a neuro-invasive disease that disproportionately affects children under the age of 16 in Southern Appalachia. The three vectors for LACV are Aedes albopictus (Skuse), Ae. japonicus (Theobald), and Ae. triseriatus (Say). Localized maps of the geographic distribution of vectors are practical tools for mosquito management personnel to target areas with high mosquito abundance. This study hypothesized that LACV vectors have unique species-specific spatial and temporal clusters. To test this, 44 sites were identified in Knox County, Tennessee for their land use/type. At each site, host-seeking mosquitoes were collected approximately every other week from May-October 2018. Spatial clusters of host-seeking mosquito collections for each of the three mosquito species were investigated using Kulldorff's spatial scan statistic, specifying a retrospective space-time Bernoulli model. Most vector clusters were identified in south-central Knox County while the seasonality of clusters varied by mosquito species. Clusters of Ae. albopictus were observed throughout the entire study period while clusters of Ae. japonicus and Ae. triseriatus only occurred May-June. The findings indicate that the relative abundance of LACV vectors were more abundant in south-central Knox County compared to the rest of the county. Of interest, these clusters spatially overlapped with previous LACE diagnosed cases. These findings are useful in guiding decisions on targeted mosquito control in Knox County and may be applied to other counties within Southern Appalachia.


Assuntos
Aedes/virologia , Comportamento Animal , Doenças Endêmicas , Interações Hospedeiro-Parasita , Vírus La Crosse/fisiologia , Análise Espaço-Temporal , Animais , Geografia , Insetos Vetores/virologia , Tennessee
14.
Waste Manag ; 117: 93-103, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32818812

RESUMO

Diffusion of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) through 0.1 mm and 0.75 mm LLDPE and 0.1 mm and 0.75 mm LLDPE coextruded with ethyl vinyl alcohol (denoted as CoEx) at room temperature (23 °C), 35 °C, and 50 °C is examined. These tests had negligible source depletion throughout the monitoring period, indicating limited contaminant partitioning and diffusion through the LLDPE. At 483 days, 23 °C receptor PFOA and PFOS concentrations, cr, were <8 µg/L (cr/co < 3.2 × 10-4) for all tests, and at 399 days elevated temperature receptor concentrations were < 0.4 µg/L (cr/co < 1.6 × 10-5) at 35 °C and <0.5 µg/L (cr/co < 2.0 × 10-5) at 50 °C for both PFOA and PFOS. LLDPE partitioning coefficient, Sgf was 0.9-1.4 (PFOA) and 2.8-5.3 (PFOS) based on sorption tests at 23 °C. Based on the best estimates of permeation coefficient, PgCoEx, for CoEx was consistently lower than PgLLDPE. For PFOA, CoEx had PgCoEx < 0.26 × 10-16 m2/s at 23 °C, <11 × 10-16 m2/s (35 °C), and < 10 × 10-16 m2/s (50 °C) while LLDPE had PgLLDPE < 3.1 × 10-16 m2/s (23 °C), <13 × 10-16 m2/s (35 °C), and <19 × 10-16 m2/s (50 °C). For PFOS, CoEx and LLDPE had PgCoEx < 0.55 × 10-16 m2/s and PgLLDPE < 3.2 × 10-16 m2/s (23 °C), PgCoEx < 8.3 × 10-16 m2/s and PgLLDPE < 40 × 10-16 m2/s (35 °C), and PgCoEx < 8.2 × 10-16 m2/s and PgLLDPE < 52 × 10-16 m2/s (50 °C). These values are preliminary and may change (e.g., decrease) as more data comes available over time. The Pg values deduced for PFOA and PFOS are remarkably lower than those reported for other contaminants of concern, excepting BPA, which exhibits similar behaviour.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Caprilatos
15.
Waste Manag ; 114: 33-42, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32650281

RESUMO

Horizontal spacing of horizontal extraction gas wells can be designed to achieve a 90% pumping rate of the total generated landfill gas (LFG) from given waste properties (viz: gas permeability, landfill gas generation and non-homogeneity with depth), cover characteristics and vacuum pressure. However, cover characteristics and vacuum pressure are also important design parameters and different combinations of them result in different distributions of gas pressure in the waste, some of which would induce problematic air intrusion while others might pose threat to cover stability. This paper uses the maximum gas pressure directly below cover to distinguish these combinations, and provides the first study of the effects of the above parameters on potential outcomes. The ability of the overlying cover to resist LFG emission from the landfilled waste is suggested not to exceed a critical value, otherwise the maximum gas pressure below it would become at least 1 kPa larger than atmospheric pressure. A design formula for this critical value is proposed with respect to typical values of waste properties, vacuum pressure and the buried depth of horizontal wells in wide ranges. Together with consideration of recovery efficiency, the proposed method can be used to design a horizontal extraction gas collection system and a cover system in better working condition, and to evaluate the maximum gas pressure below cover. These applications are illustrated by a worked example.


Assuntos
Poluentes Atmosféricos/análise , Eliminação de Resíduos , Metano/análise , Campos de Petróleo e Gás , Instalações de Eliminação de Resíduos
16.
J Vector Ecol ; 45(1): 2-15, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32492282

RESUMO

Interspecific associations between two mosquito species can lead to effects such as competition, species displacement, and species stability. To better understand Aedes albopictus (Skuse) and other Aedes species, we monitored eggs in artificial oviposition cups (ovitraps) within Knox County, TN, U.S.A., during the 2016 and 2017 mosquito seasons. In 2016, one black and one white ovitrap were placed at 18 sites for 21 weeks, while in 2017 black and white ovitraps baited with grass-infused or deionized water were placed at 11 sites for nine weeks. Eggs were identified to species and resulting counts were used to determine the degree of interspecific association using Cole's coefficients (C7 ) and the degree of heterogeneity across space and time using generalized linear mixed models (GLMM). Here, Aedes mosquitoes are generally ovipositing in black cups with grass-infused water, and Ae. albopictus eggs co-occurred with other Aedes species more often than would be expected. Finding a positive significant interspecific association between Ae. albopictus and other Aedes eggs suggests that methods used to control Ae. albopictus may also control other Aedes mosquitoes. Finding that Ae. albopictus co-occurs with other Aedes mosquitoes warrants additional research to evaluate outcomes associated with co-occurrence within the study area.


Assuntos
Aedes/fisiologia , Oviposição/fisiologia , Animais , Ecologia , Feminino , Tennessee
17.
BJOG ; 127(13): 1665-1675, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32437088

RESUMO

OBJECTIVE: To review quality of care in births planned in midwifery-led settings, resulting in an intrapartum-related perinatal death. DESIGN: Confidential enquiry. SETTING: England, Scotland and Wales. SAMPLE: Intrapartum stillbirths and intrapartum-related neonatal deaths in births planned in alongside midwifery units, freestanding midwifery units or at home, sampled from national perinatal surveillance data for 2015/16 (alongside midwifery units) and 2013-16 (freestanding midwifery units and home births). METHODS: Multidisciplinary panels reviewed medical notes for each death, assessing and grading quality of care by consensus, with reference to national standards and guidance. Data were analysed using thematic analysis and descriptive statistics. RESULTS: Sixty-four deaths were reviewed, 30 stillbirths and 34 neonatal deaths. At the start of labour care, 23 women were planning birth in an alongside midwifery unit, 26 in a freestanding midwifery unit and 15 at home. In 75% of deaths, improvements in care were identified that may have made a difference to the outcome for the baby. Improvements in care were identified that may have made a difference to the mother's physical and psychological health and wellbeing in 75% of deaths. Issues with care were identified around risk assessment and decisions about planning place of birth, intermittent auscultation, transfer during labour, resuscitation and neonatal transfer, follow up and local review. CONCLUSIONS: These confidential enquiry findings do not address the overall safety of midwifery-led settings for healthy women with straightforward pregnancies, but suggest areas where the safety of care can be improved. Maternity services should review their care with respect to our recommendations. TWEETABLE ABSTRACT: Confidential enquiry of intrapartum-related baby deaths highlights areas where care in midwifery-led settings can be made even safer.


Assuntos
Parto Domiciliar/normas , Tocologia/normas , Morte Perinatal , Qualidade da Assistência à Saúde , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Recém-Nascido , Gravidez , Reino Unido
18.
Proc Natl Acad Sci U S A ; 117(9): 4653-4663, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32060122

RESUMO

The LIN28:pre-let-7:TUTase ternary complex regulates pluripotency and oncogenesis by controlling processing of the let-7 family of microRNAs. The complex oligouridylates the 3' ends of pre-let-7 molecules, leading to their degradation via the DIS3L2 exonuclease. Previous studies suggest that components of this complex are potential therapeutic targets in malignancies that aberrantly express LIN28. In this study we developed a functional epitope selection approach to identify nanobody inhibitors of the LIN28:pre-let-7:TUT4 complex. We demonstrate that one of the identified nanobodies, Nb-S2A4, targets the 106-residue LIN28:let-7 interaction (LLI) fragment of TUT4. Nb-S2A4 can effectively inhibit oligouridylation and monouridylation of pre-let-7g in vitro. Expressing Nb-S2A4 allows maturation of the let-7 species in cells expressing LIN28, highlighting the therapeutic potential of targeting the LLI fragment.


Assuntos
Proteínas de Ligação a DNA/imunologia , MicroRNAs/metabolismo , Processamento de Terminações 3' de RNA , Anticorpos de Domínio Único/imunologia , Animais , Sítios de Ligação , Proteínas de Ligação a DNA/química , Células HEK293 , Células HeLa , Humanos , Camundongos , MicroRNAs/genética , Ligação Proteica , Estabilidade de RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Células Sf9 , Spodoptera
19.
Waste Manag ; 100: 18-27, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494403

RESUMO

The decrease in stress crack resistance (SCR) of geomembranes (GMBs) due to physical ageing is examined. It is shown that the SCR of a 1.5 mm high density polyethylene (HDPE) GMB immersed in municipal solid waste (MSW) leachate, deionized (DI) water, and air experienced a decrease to an equilibrium value, denoted herein as SCRm, in a few months and then did not change for the remainder of a 116-month test. The same GMB was also immersed in basic mining pregnant leach solution (PLS) and brine and a similar decrease in SCR to SCRm was observed in the first three months. For this GMB, SCRm was about 50% of the initial SCR value (i.e., SCRm ∼ 0.5·SCRo) for all incubation fluids examined. It is then shown that this behaviour is not unique. Seven other high density polyethylene (HDPE) and one blended polyolefin (BPO) GMBs are shown to experience a decrease in SCR to 0.17·SCRo ≤ SCRm ≤ 0.56·SCRo without any evidence of oxidative degradation. The magnitude of SCRm is shown to be product specific. In contrast, the one linear low density polyethylene (LLDPE) examined exhibited no such physical ageing. The implications for designing with GMBs are discussed.


Assuntos
Eliminação de Resíduos , Gerenciamento de Resíduos , Polienos , Polietileno , Resíduos Sólidos , Instalações de Eliminação de Resíduos
20.
Waste Manag ; 98: 102-112, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31442851

RESUMO

Considering exponential decreases in gas permeability and gas generation of waste with depth, a two-dimensional analytical model is developed to describe the landfill gas (LFG) recovery using horizontal wells. This model is used to simulate more than 680,000 scenarios involving typical values of waste properties, cover characteristics and design parameters for horizontal wells (seven variables in total). The coupled effect of these seven variables on air intrusion and the gas recovery efficiency of horizontal wells are investigated. It is shown that all the variables examined, except for the two variables defining waste non-homogeneity, could be integrated into three dimensionless variables. The horizontal spacing and buried depth of horizontal wells are examined as a function of cover characteristics, waste properties, and vacuum pressure to allow the development of a generalized design method for horizontal wells. An upper limit of horizontal well spacing is defined (for an 85% recovery rate) and a simple formula is provided which can be used to estimate the corresponding level of air intrusion. The upper limit spacing is shown to be affected by the non-homogeneity in gas permeability of waste, cover characteristics, and buried well depth. Using a worked example, the proposed method is shown to be capable of estimating air intrusion into existing horizontal gas collection wells and to optimize the design of horizontal wells considering waste non-homogeneity.


Assuntos
Poluentes Atmosféricos , Eliminação de Resíduos , Metano , Instalações de Eliminação de Resíduos
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