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1.
Nat Food ; 4(8): 654-663, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37591963

RESUMO

Agricultural irrigation induces greenhouse gas emissions directly from soils or indirectly through the use of energy or construction of dams and irrigation infrastructure, while climate change affects irrigation demand, water availability and the greenhouse gas intensity of irrigation energy. Here, we present a scoping review to elaborate on these irrigation-climate linkages by synthesizing knowledge across different fields, emphasizing the growing role climate change may have in driving future irrigation expansion and reinforcing some of the positive feedbacks. This Review underscores the urgent need to promote and adopt sustainable irrigation, especially in regions dominated by strong, positive feedbacks.


Assuntos
Gases de Efeito Estufa , Retroalimentação , Irrigação Agrícola , Mudança Climática , Conhecimento
2.
Environ Sci Technol ; 57(31): 11499-11509, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37498168

RESUMO

The United States may produce as much as 45% of its electricity using solar energy technology by 2050, which could require more than 40,000 km2 of land to be converted to large-scale solar energy production facilities. Little is known about how such development may impact animal movement. Here, we use five spatially explicit projections of solar energy development through 2050 to assess the extent to which ground-mounted photovoltaic solar energy expansion in the continental United States may impact land-cover and alter areas important for animal movement. Our results suggest that there could be a substantial overlap between solar energy development and land important for animal movement: across projections, 7-17% of total development is expected to occur on land with high value for movement between large protected areas, while 27-33% of total development is expected to occur on land with high value for climate-change-induced migration. We also found substantial variation in the potential overlap of development and land important for movement at the state level. Solar energy development, and the policies that shape it, may align goals for biodiversity and climate change by incorporating the preservation of animal movement as a consideration in the planning process.


Assuntos
Energia Solar , Animais , Estados Unidos , Biodiversidade , Mudança Climática , Eletricidade , Previsões , Ecossistema , Conservação dos Recursos Naturais
3.
Drug Metab Dispos ; 51(9): 1207-1215, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37230767

RESUMO

Pregnane X receptor (PXR) is a xenobiotic receptor that can be activated by numerous chemicals including endogenous hormones, dietary steroids, pharmaceutical agents, and environmental chemicals. PXR has been established to function as a xenobiotic sensor to coordinately regulate xenobiotic metabolism by regulating the expression of many enzymes and transporters required for xenobiotic metabolism. Recent studies have implicated a potentially important role for PXR in obesity and metabolic disease beyond xenobiotic metabolism, but how PXR action in different tissues or cell types contributes to obesity and metabolic disorders remains elusive. To investigate the role of adipocyte PXR in obesity, we generated a novel adipocyte-specific PXR deficient mouse model (PXRΔAd). Notably, we found that loss of adipocyte PXR did not affect food intake, energy expenditure, and obesity in high-fat diet-fed male mice. PXRΔAd mice also had similar obesity-associated metabolic disorders including insulin resistance and hepatic steatosis as control littermates. PXR deficiency in adipocytes did not affect expression of key adipose genes in PXRΔAd mice. Our findings suggest that adipocyte PXR signaling may be dispensable in diet-induced obesity and metabolic disorders in mice. Further studies are needed to understand the role of PXR signaling in obesity and metabolic disorders in the future. SIGNIFICANCE STATEMENT: The authors demonstrate that deficiency of adipocyte pregnane X receptor (PXR) does not affect diet-induced obesity or metabolic disorders in mice and infers that adipocyte PXR signaling may not play a key role in diet-induced obesity. More studies are needed to understand the tissue-specific role of PXR in obesity.


Assuntos
Resistência à Insulina , Receptores de Esteroides , Masculino , Camundongos , Animais , Receptor de Pregnano X/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Xenobióticos/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Adipócitos/metabolismo , Dieta Hiperlipídica/efeitos adversos
4.
J Lipid Res ; 64(4): 100352, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36871792

RESUMO

Small noncoding RNAs (sncRNAs) play diverse roles in numerous biological processes. While the widely used RNA sequencing (RNA-Seq) method has advanced sncRNA discovery, RNA modifications can interfere with the complementary DNA library construction process, preventing the discovery of highly modified sncRNAs including transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs) that may have important functions in disease development. To address this technical obstacle, we recently developed a novel PANDORA-Seq (Panoramic RNA Display by Overcoming RNA Modification Aborted Sequencing) method to overcome RNA modification-elicited sequence interferences. To identify novel sncRNAs associated with atherosclerosis development, LDL receptor-deficient (LDLR-/-) mice were fed a low-cholesterol diet or high-cholesterol diet (HCD) for 9 weeks. Total RNAs isolated from the intima were subjected to PANDORA-Seq and traditional RNA-Seq. By overcoming RNA modification-elicited limitations, PANDORA-Seq unveiled an rsRNA/tsRNA-enriched sncRNA landscape in the atherosclerotic intima of LDLR-/- mice, which was strikingly different from that detected by traditional RNA-Seq. While microRNAs were the dominant sncRNAs detected by traditional RNA-Seq, PANDORA-Seq substantially increased the reads of rsRNAs and tsRNAs. PANDORA-Seq also detected 1,383 differentially expressed sncRNAs induced by HCD feeding, including 1,160 rsRNAs and 195 tsRNAs. One of HCD-induced intimal tsRNAs, tsRNA-Arg-CCG, may contribute to atherosclerosis development by regulating the proatherogenic gene expression in endothelial cells. Overall, PANDORA-Seq revealed a hidden rsRNA and tsRNA population associated with atherosclerosis development. These understudied tsRNAs and rsRNAs, which are much more abundant than microRNAs in the atherosclerotic intima of LDLR-/- mice, warrant further investigations.


Assuntos
MicroRNAs , Pequeno RNA não Traduzido , Camundongos , Animais , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo , Células Endoteliais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores de LDL/genética , Colesterol
5.
Environ Int ; 172: 107769, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36709676

RESUMO

Exposure to ubiquitous plastic-associated endocrine disrupting chemicals (EDCs) is associated with the increased risk of many chronic diseases. For example, phthalate exposure is associated with cardiometabolic mortality in humans, with societal costs ∼ $39 billion/year or more. We recently demonstrated that several widely used plastic-associated EDCs increase cardiometabolic disease in appropriate mouse models. In addition to affecting adult health, parental exposure to EDCs has also been shown to cause metabolic disorders, including obesity and diabetes, in the offspring. While most studies have focused on the impact of maternal EDC exposure on the offspring's health, little is known about the effects of paternal EDC exposure. In the current study, we investigated the adverse impact of paternal exposure to a ubiquitous but understudied phthalate, dicyclohexyl phthalate (DCHP) on the metabolic health of F1 and F2 offspring in mice. Paternal DCHP exposure led to exacerbated insulin resistance and impaired insulin signaling in F1 offspring without affecting diet-induced obesity. We previously showed that sperm small non-coding RNAs including tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs) contribute to the intergenerational transmission of paternally acquired metabolic disorders. Using a novel PANDORA-seq, we revealed that DCHP exposure can lead to sperm tsRNA/rsRNA landscape changes that were undetected by traditional RNA-seq, which may contribute to DCHP-elicited adverse effects. Lastly, we found that paternal DCHP can also cause sex-specific transgenerational adverse effects in F2 offspring and elicited glucose intolerance in female F2 descendants. Our results suggest that exposure to endocrine disrupting phthalates may have intergenerational and transgenerational adverse effects on the metabolic health of their offspring. These findings increase our understanding of the etiology of chronic human diseases originating from chemical-elicited intergenerational and transgenerational effects.


Assuntos
Doenças Metabólicas , Exposição Paterna , Humanos , Adulto , Camundongos , Animais , Masculino , Feminino , Exposição Paterna/efeitos adversos , Sêmen/metabolismo , Espermatozoides , Doenças Metabólicas/induzido quimicamente , Obesidade/metabolismo
6.
J Pharm Pract ; : 8971900221144399, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36469659

RESUMO

BACKGROUND: Involvement of Clinical Pharmacy Specialists (CPS) in the care of patients with diabetes mellitus (DM) has been demonstrated to be beneficial. Whether this positive impact applies to increased use of cardiovascular risk-reducing medications is less well established. OBJECTIVE: To determine the association of CPS co-management on the prescription of diabetes medications with proven cardiovascular benefits for patients with DM and established cardiovascular disease in the primary care setting. METHODS: This retrospective cohort study evaluated patients in a Veterans Affairs health-system in primary care settings from February 1, 2019, through January 31, 2020. Patients were included if they had type 2 DM treated with at least one medication and had CVD. Patients were grouped into two cohorts for comparison, those with CPS co-management and those without. The primary outcome was the proportion of patients in each group with new prescriptions for empagliflozin or liraglutide initiated during the study timeframe. RESULTS: In total, 8058 patients were found eligible for inclusion in the study. Clinical co-management by a CPS was provided to 2099 patients. Study medications were prescribed, approved, and initiated in 596 patients during the study period, including 391 (18.6%) in the CPS group and 205 (3.4%) in the non-CPS group (P < .001). CONCLUSION: This study showed CPS involvement is associated with increased prescribing of diabetes medications with proven cardiovascular benefits.

7.
J Environ Manage ; 324: 116410, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36352716

RESUMO

Floating solar photovoltaic (FPV) deployments are increasing globally as the switch to renewable energy intensifies, representing a considerable water surface transformation. FPV installations can potentially impact aquatic ecosystem function, either positively or negatively. However, these impacts are poorly resolved given the challenges of collecting empirical data for field or modelling experiments. In particular, there is limited evidence on the response of phytoplankton to changes in water body thermal dynamics and light climate with FPV. Given the importance of understanding phytoplankton biomass and species composition for managing ecosystem services, we use an uncertainty estimation approach to simulate the effect of FPV coverage and array siting location on a UK reservoir. FPV coverage was modified in 10% increments from a baseline with 0% coverage to 100% coverage for three different FPV array siting locations based on reservoir circulation patterns. Results showed that FPV coverage significantly impacted thermal properties, resulting in highly variable impacts on phytoplankton biomass and species composition. The impacts on phytoplankton were often dependent on array siting location as well as surface coverage. Changes to phytoplankton species composition were offset by the decrease in phytoplankton biomass associated with increasing FPV coverage. We identified that similar phytoplankton biomass reductions could be achieved with less FPV coverage by deploying the FPV array on the water body's faster-flowing area than the central or slower flowing areas. The difference in response dependent on siting location could be used to tailor phytoplankton management in water bodies. Simulation of water body-FPV interactions efficiently using an uncertainty approach is an essential tool to rapidly develop understanding and ultimately inform FPV developers and water body managers looking to minimise negative impacts and maximise co-benefits.


Assuntos
Ecossistema , Fitoplâncton , Biomassa , Luz Solar , Água
8.
PLoS One ; 17(7): e0270155, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35793381

RESUMO

The global energy system has a relatively small land footprint at present, comprising just 0.4% of ice-free land. This pales in comparison to agricultural land use- 30-38% of ice-free land-yet future low-carbon energy systems that shift to more extensive technologies could dramatically alter landscapes around the globe. The challenge is more acute given the projected doubling of global energy consumption by 2050 and widespread electrification of transportation and industry. Yet unlike greenhouse gas emissions, land use intensity of energy has been rarely studied in a rigorous way. Here we calculate land-use intensity of energy (LUIE) for real-world sites across all major sources of electricity, integrating data from published literature, databases, and original data collection. We find a range of LUIE that span four orders of magnitude, from nuclear with 7.1 ha/TWh/y to dedicated biomass at 58,000 ha/TWh/y. By applying these LUIE results to the future electricity portfolios of ten energy scenarios, we conclude that land use could become a significant constraint on deep decarbonization of the power system, yet low-carbon, land-efficient options are available.


Assuntos
Agricultura , Eletricidade , Biomassa , Carbono , Dióxido de Carbono
9.
R Soc Open Sci ; 9(3): 211558, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35360356

RESUMO

Renewable energy production can kill individual birds, but little is known about how it affects avian populations. We assessed the vulnerability of populations for 23 priority bird species killed at wind and solar facilities in California, USA. Bayesian hierarchical models suggested that 48% of these species were vulnerable to population-level effects from added fatalities caused by renewables and other sources. Effects of renewables extended far beyond the location of energy production to impact bird populations in distant regions across continental migration networks. Populations of species associated with grasslands where turbines were located were most vulnerable to wind. Populations of nocturnal migrant species were most vulnerable to solar, despite not typically being associated with deserts where the solar facilities we evaluated were located. Our findings indicate that addressing declines of North American bird populations requires consideration of the effects of renewables and other anthropogenic threats on both nearby and distant populations of vulnerable species.

10.
Theranostics ; 12(6): 2639-2657, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401811

RESUMO

Rationale: Macrophages are the frontline immune cells in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Angiotensin-converting enzyme 2 (ACE2) serves as the binding receptor to SARS-CoV-2 Spike glycoprotein for fusion and internalization into the human host cells. However, the mechanisms underlying SARS-CoV-2-elicited macrophage inflammatory responses remain elusive. Neutralizing SARS-CoV-2 by human ACE2 (hACE2) decoys has been proposed as a therapeutic approach to ameliorate SARS-CoV-2-stimulated inflammation. This study aims to investigate whether an engineered decoy receptor can abrogate SARS-CoV-2-induced macrophage inflammation. Methods: hACE2 was biotinylated to the surface of nano-liposomes (d = 100 nm) to generate Liposome-human ACE2 complex (Lipo-hACE2). Lentivirus expressing Spike protein (D614G) was also created as a pseudo-SARS-CoV-2 (Lenti-Spike). Liposome-hACE2 was used as a decoy receptor or competitive inhibitor to inhibit SARS-CoV-2 or Lenti-Spike-induced macrophage inflammation in vitro and in vivo. Results: Both SARS-CoV-2 and Lenti-Spike stimulated strong inflammatory responses by inducing the expression of key cytokine and chemokines, including IL-1ß, IL-6, TNFα, CCL-2, and CXCL-10, in murine and human macrophages in vitro, whereas Lipo-hACE2 decoy abolished these effects in macrophages. Furthermore, intravenous injection of Lenti-Spike led to increased macrophage and tissue inflammation in wild type mice, which was also abolished by Lipo-hACE2 treatment. Mechanistically, Spike protein stimulated macrophage inflammation by activating canonical NF-κB signaling. RNA sequencing analysis revealed that Lenti-Spike induced over 2,000 differentially expressed genes (DEGs) in murine macrophages, but deficiency of IκB kinase ß (IKKß), a key regulator for NF-κB activation, abrogated Lenti-Spike-elicited macrophage inflammatory responses. Conclusions: We demonstrated that the engineered Lipo-hACE2 acts as a molecular decoy to neutralize SARS-CoV-2 or Spike protein-induced inflammation in both murine and human macrophages, and activation of the canonical IKKß/NF-κB signaling is essential for SARS-CoV-2-elicited macrophage inflammatory responses.


Assuntos
Tratamento Farmacológico da COVID-19 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2 , Animais , Humanos , Quinase I-kappa B , Inflamação , Lipossomos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo
11.
Cells ; 11(7)2022 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-35406689

RESUMO

Plastic-associated endocrine disrupting chemicals (EDCs) have been implicated in the etiology of cardiovascular disease (CVD) in humans, but the underlying mechanisms remain elusive. Dicyclohexyl phthalate (DCHP) is a widely used phthalate plasticizer; whether and how exposure to DCHP elicits adverse effects in vivo is mostly unknown. We previously reported that DCHP is a potent ligand of the pregnane X receptor (PXR) which acts as a xenobiotic sensor to regulate xenobiotic metabolism. PXR also functions in macrophages to regulate atherosclerosis development in animal models. In the current study, LDL receptor-deficient mice with myeloid-specific PXR deficiency (PXRΔMyeLDLR-/-) and their control littermates (PXRF/FLDLR-/-) were used to determine the impact of DCHP exposure on macrophage function and atherosclerosis. Chronic exposure to DCHP significantly increased atherosclerotic lesion area in the aortic root and brachiocephalic artery of PXRF/FLDLR-/- mice by 65% and 77%, respectively. By contrast, DCHP did not affect atherosclerosis development in PXRΔMyeLDLR-/- mice. Exposure to DCHP led to elevated expression of the scavenger receptor CD36 in macrophages and increased macrophage form cell formation in PXRF/FLDLR-/- mice. Our findings provide potential mechanisms underlying phthalate-associated CVD risk and will ultimately stimulate further investigations and mitigation of the adverse effects of plastic-associated EDCs on CVD risk in humans.


Assuntos
Aterosclerose , Disruptores Endócrinos , Receptor de Pregnano X , Animais , Aterosclerose/metabolismo , Camundongos , Camundongos Knockout , Ácidos Ftálicos , Plásticos , Receptor de Pregnano X/genética , Receptores de LDL/genética , Xenobióticos
12.
Cardiovasc Drugs Ther ; 36(2): 201-215, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-33459922

RESUMO

PURPOSE: HIV infection is consistently associated with an increased risk of atherosclerotic cardiovascular disease, but the underlying mechanisms remain elusive. HIV protein Tat, a transcriptional activator of HIV, has been shown to activate NF-κB signaling and promote inflammation in vitro. However, the atherogenic effects of HIV Tat have not been investigated in vivo. Macrophages are one of the major cell types involved in the initiation and progression of atherosclerosis. We and others have previously revealed the important role of IκB kinase ß (IKKß), a central inflammatory coordinator through activating NF-κB, in the regulation of macrophage functions and atherogenesis. This study investigated the impact of HIV Tat exposure on macrophage functions and atherogenesis. METHODS: To investigate the effects of Tat on macrophage IKKß activation and atherosclerosis development in vivo, myeloid-specific IKKß-deficient LDLR-deficient (IKKßΔMyeLDLR-/-) mice and their control littermates (IKKßF/FLDLR-/-) were exposed to recombinant HIV protein Tat. RESULTS: Exposure to Tat significantly increased atherosclerotic lesion size and plaque vulnerability in IKKßF/FLDLR-/- but not IKKßΔMyeLDLR-/- mice. Deficiency of myeloid IKKß attenuated Tat-elicited macrophage inflammatory responses and atherosclerotic lesional inflammation in IKKßΔMyeLDLR-/- mice. Further, RNAseq analysis demonstrated that HIV protein Tat affects the expression of many atherosclerosis-related genes in vitro in an IKKß-dependent manner. CONCLUSIONS: Our findings reveal atherogenic effects of HIV protein Tat in vivo and demonstrate a pivotal role of myeloid IKKß in Tat-driven atherogenesis.


Assuntos
Aterosclerose , Infecções por HIV , Animais , Aterosclerose/metabolismo , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Infecções por HIV/patologia , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Inflamação/metabolismo , Lipoproteínas LDL , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases , Receptores de LDL/metabolismo
13.
Environ Health Perspect ; 129(12): 127001, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34851150

RESUMO

BACKGROUND: Exposure to plastic-associated endocrine disrupting chemicals (EDCs) has been associated with an increased risk of cardiovascular disease (CVD) in humans. However, the underlying mechanisms for this association are unclear. Many EDCs have been shown to function as ligands of the nuclear receptor pregnane X receptor (PXR), which functions as xenobiotic sensor but also has pro-atherogenic effects in vivo. OBJECTIVE: We sought to investigate the contribution of PXR to the adverse effects dicyclohexyl phthalate (DCHP), a widely used phthalate plasticizer, on lipid homeostasis and CVD risk factors. METHODS: Cell-based assays, primary organoid cultures, and PXR conditional knockout and PXR-humanized mouse models were used to investigate the impact of DCHP exposure on PXR activation and lipid homeostasis in vitro and in vivo. Targeted lipidomics were performed to measure circulating ceramides, novel predictors for CVD. RESULTS: DCHP was identified as a potent PXR-selective agonist that led to higher plasma cholesterol levels in wild-type mice. DCHP was then demonstrated to activate intestinal PXR to elicit hyperlipidemia by using tissue-specific PXR-deficient mice. Interestingly, DCHP exposure also led to higher circulating ceramides in a PXR-dependent manner. DCHP-mediated PXR activation stimulated the expression of intestinal genes mediating lipogenesis and ceramide synthesis. Given that PXR exhibits considerable species-specific differences in receptor pharmacology, PXR-humanized mice were also used to replicate these findings. DISCUSSION: Although the adverse health effects of several well-known phthalates have attracted considerable attention, little is known about the potential impact of DCHP on human health. Our studies demonstrate that DCHP activated PXR to induce hypercholesterolemia and ceramide production in mice. These results indicate a potentially important role of PXR in contributing to the deleterious effects of plastic-associated EDCs on cardiovascular health in humans. Testing PXR activation should be considered for risk assessment of phthalates and other EDCs. https://doi.org/10.1289/EHP9262.


Assuntos
Receptores de Esteroides , Animais , Homeostase , Lipídeos , Camundongos , Camundongos Knockout , Ácidos Ftálicos , Receptor de Pregnano X , Receptores de Esteroides/agonistas , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo
14.
Front Cardiovasc Med ; 8: 752337, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34957242

RESUMO

Cardiometabolic diseases, including cardiovascular disease, obesity, and diabetes, are the leading cause of mortality and morbidity worldwide. Cardiometabolic diseases are associated with many overlapping metabolic syndromes such as hypertension, hyperlipidemia, insulin resistance, and central adiposity. However, the underlying causes of cardiometabolic diseases and associated syndromes remain poorly understood. Within the past couple of decades, considerable progresses have been made to understand the role of inflammatory signaling in the pathogenesis of cardiometabolic diseases. The transcription factor, NF-κB, a master regulator of the innate and adaptive immune responses, is highly active in cardiometabolic diseases. IκB kinase ß (IKKß), the predominant catalytic subunit of the IKK complex, is required for canonical activation of NF-κB, and has been implicated as the critical molecular link between inflammation and cardiometabolic diseases. Recent studies have revealed that IKKß has diverse and unexpected roles in mediating adiposity, insulin sensitivity, glucose homeostasis, vascular function, and atherogenesis through complex mechanisms. IKKß has been demonstrated as a critical player in the development of cardiometabolic diseases and is implicated as a promising therapeutic target. This review summarizes current knowledge of the functions of IKKß in mediating the development and progression of cardiometabolic diseases.

15.
JCI Insight ; 6(18)2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34324438

RESUMO

Cardiac inflammation and fibrosis contribute significantly to hypertension-related adverse cardiac remodeling. IκB kinase ß (IKK-ß), a central coordinator of inflammation through activation of NF-κB, has been demonstrated as a key molecular link between inflammation and cardiovascular disease. However, the cell-specific contribution of IKK-ß signaling toward adverse cardiac remodeling remains elusive. Cardiac fibroblasts are one of the most populous nonmyocyte cell types in the heart that play a key role in mediating cardiac fibrosis and remodeling. To investigate the function of fibroblast IKK-ß, we generated inducible fibroblast-specific IKK-ß-deficient mice. Here, we report an important role of IKK-ß in the regulation of fibroblast functions and cardiac remodeling. Fibroblast-specific IKK-ß-deficient male mice were protected from angiotensin II-induced cardiac hypertrophy, fibrosis, and macrophage infiltration. Ablation of fibroblast IKK-ß inhibited angiotensin II-stimulated fibroblast proinflammatory and profibrogenic responses, leading to ameliorated cardiac remodeling and improved cardiac function in IKK-ß-deficient mice. Findings from this study establish fibroblast IKK-ß as a key factor regulating cardiac fibrosis and function in hypertension-related cardiac remodeling.


Assuntos
Angiotensina II/farmacologia , Cardiomegalia/genética , Fibroblastos/fisiologia , Quinase I-kappa B/genética , Miocárdio/patologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Diferenciação Celular/efeitos dos fármacos , Movimento Celular , Proliferação de Células , Células Cultivadas , Colágeno Tipo I/metabolismo , Fibrose , Técnicas de Silenciamento de Genes , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/induzido quimicamente , Inflamação/metabolismo , Macrófagos , Masculino , Camundongos , Miocardite/genética , Miocardite/metabolismo , Tamanho do Órgão , Fatores de Proteção , Transdução de Sinais , Remodelação Ventricular/genética
16.
Ecol Appl ; 31(6): e02349, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33817888

RESUMO

Political and economic initiatives intended to increase energy production while reducing carbon emissions are driving demand for solar energy. Consequently, desert regions are now targeted for development of large-scale photovoltaic solar energy facilities. Where vegetation communities are left intact or restored within facilities, ground-mounted infrastructure may have negative impacts on desert-adapted plants because it creates novel rainfall runoff and shade conditions. We used experimental solar arrays in the Mojave Desert to test how these altered conditions affect population dynamics for a closely related pair of native annual plants: rare Eriophyllum mohavense and common E. wallacei. We estimated aboveground demographic rates (seedling emergence, survivorship, and fecundity) over 7 yr and used seed bank survival rates from a concurrent study to build matrix models of population growth in three experimental microhabitats. In drier years, shade tended to reduce survival of the common species, but increase survival of the rare species. In a wet year, runoff from panels tended to increase seed output for both species. Population growth projections from microhabitat-specific matrix models showed stronger effects of microhabitat under wetter conditions, and relatively little effect under dry conditions (lack of rainfall was an overwhelming constraint). Performance patterns across microhabitats in the wettest year differed between rare and common species. Projected growth of E. mohavense was substantially reduced in shade, mediated by negative effects on aboveground demographic rates. Hence, the rare species were more susceptible to negative effects of panel infrastructure in wet years that are critical to seed bank replenishment. Our results suggest that altered shade and water runoff regimes associated with energy infrastructure will have differential effects on demographic transitions across annual species and drive population-level processes that determine local abundance, resilience, and persistence.


Assuntos
Asteraceae , Clima Desértico , Ecossistema , Energia Solar , Dinâmica Populacional , Sementes
17.
J Am Acad Orthop Surg ; 29(14): e702-e713, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33878082

RESUMO

Pediatric patients may benefit from extremity amputations with potential prosthetic fitting when addressing limb deficiencies, trauma, infection, limb ischemia, or other pathologies. The performance of a quality amputation is a fundamental skill to an orthopaedic surgeon, yet avoidance of pitfalls can be elusive in children. The need for surgical precision and sound decision-making is amplified in pediatric amputations, where the skeleton is dynamic and growing, anatomy can be miniscule and (in the case of congenital anomalies) variable. The principles that guide amputation level and technical approach are unique in children. Despite this, descriptions of these procedures as they should be applied to a growing or congenitally deficient skeleton are lacking. Furthermore, surgeons must also understand the unique prosthetic and psychosocial considerations for children. A collaborative approach between the surgeons, rehabilitation physicians, prosthetists, therapists, and families is essential to ensuring optimal results.


Assuntos
Membros Artificiais , Cirurgiões , Amputação Cirúrgica , Criança , Humanos , Implantação de Prótese
18.
J Water Health ; 18(5): 766-775, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33095199

RESUMO

Coliforms are important bacterial contamination indicators in recreational waters. Little is known about the antibiotic resistance of coliforms from Southern California beaches. This study examined the numbers of coliforms as well as the incidence of antibiotic-resistant coliforms in beaches with restricted and non-restricted wave action by sampling from the shores of both types of beaches following dry and wet weather. Total coliforms were selected by membrane filtration onto mEndo agar and then enumerated. Randomly selected isolates from each location were screened for resistance to nine classes of antibiotics by disk diffusion, and the multiple antibiotic resistance (MAR) index was calculated. Numbers of total coliforms were significantly higher following rain compared to dry weather. Total coliform numbers were not significantly elevated at non-restricted wave action sites. Restricted wave action sites had a 78.5% increase in MAR index following wet weather compared to dry weather. Resistance to ampicillin was observed in almost 50% of isolates and was not significantly impacted by wave action or weather. Minimum inhibitory concentration testing revealed that many isolates were highly resistant to ampicillin. This study is the first to report on the antibiotic resistance of coliforms found in Southern California beaches and highlights the prevalence of ampicillin resistance.


Assuntos
Resistência Microbiana a Medicamentos , Microbiologia da Água , California/epidemiologia , Incidência , Testes de Sensibilidade Microbiana
19.
Plants (Basel) ; 9(9)2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32878043

RESUMO

Seed bank survival underpins plant population persistence but studies on seed bank trait-environment interactions are few. Changes in environmental conditions relevant to seed banks occur in desert ecosystems owing to solar energy development. We developed a conceptual model of seed bank survival to complement methodologies using in-situ seed bank packets. Using this framework, we quantified the seed bank survival of two closely related annual desert plant species, one rare (Eriophyllum mohavense) and one common (Eriophyllum wallacei), and the seed bank-environment interactions of these two species in the Mojave Desert within a system that emulates microhabitat variation associated with solar energy development. We tracked 4860 seeds buried across 540 seed packets and found, averaged across both species, that seed bank survival was 21% and 6% for the first and second growing seasons, respectively. After two growing seasons, the rare annual had a significantly greater seed bank survival (10%) than the common annual (2%). Seed bank survival across both species was significantly greater in shade (10%) microhabitats compared to runoff (5%) and control microhabitats (3%). Our study proffers insight into this early life-stage across rare and common congeners and their environmental interactions using a novel conceptual framework for seed bank survival.

20.
Insects ; 11(5)2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32438741

RESUMO

The purpose of this study was to assess the ecological knowledge surrounding the western queen butterfly, Danaus gilippus thersippus (H. Bates). Specifically, our objectives were to synthesize existing data and knowledge on the ecology of the queen and use results of this assessment to inform the direction of future research on this understudied species. We identified six core areas for assessment: distribution, the biodiversity of plant resources, western queen and their host plant phenology, chemical ecology, and four key life history traits. We mapped the distribution of D. g. thersippus from museum specimen records, citizen science (e.g., iNaturalist) and image sharing app-based observations, along with other observational data enumerating all current known plant resources and long-range movements. We assembled 14 larval food plants, six pyrrolizidine alkaloids plants and six nectar plants distributed in the western Mojave and Sonoran Desert regions of the United States and Baja California. We report on its phenology and its long-range movement. Butterfly species have declined across the western US, and western monarch populations have declined by 97%. Danaus g. thersippus has received little research attention compared with its famous congener D. plexippus L. Danaus g. thersippus' desert distribution may be at its temperature limits for the species distribution and for its rare host plant Asclepias nyctaginifolia.

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