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Cartilage, a flexible and smooth connective tissue that envelops the surfaces of synovial joints, relies on chondrocytes for extracellular matrix (ECM) production and the maintenance of its structural and functional integrity. Melatonin (MT), renowned for its anti-inflammatory and antioxidant properties, holds the potential to modulate cartilage regeneration and degradation. Therefore, the present study was devoted to elucidating the mechanism of MT on chondrocytes. The in vivo experiment consisted of three groups: Sham (only the skin tissue was incised), Model (using the anterior cruciate ligament transection (ACLT) method), and MT (30 mg/kg), with sample extraction following 12 weeks of administration. Pathological alterations in articular cartilage, synovium, and subchondral bone were evaluated using Safranin O-fast green staining. Immunohistochemistry (ICH) analysis was employed to assess the expression of matrix degradation-related markers. The levels of serum cytokines were quantified via Enzyme-linked immunosorbent assay (ELISA) assays. In in vitro experiments, primary chondrocytes were divided into Control, Model, MT, negative control, and inhibitor groups. Western blotting (WB) and Quantitative RT-PCR (q-PCR) were used to detect Silent information regulator transcript-1 (SIRT1)/Nuclear factor kappa-B (NF-κB)/Nuclear factor erythroid-2-related factor 2 (Nrf2)/Transforming growth factor-beta (TGF-ß)/Bone morphogenetic proteins (BMPs)-related indicators. Immunofluorescence (IF) analysis was employed to examine the status of type II collagen (COL2A1), SIRT1, phosphorylated NF-κB p65 (p-p65), and phosphorylated mothers against decapentaplegic homolog 2 (p-Smad2). In vivo results revealed that the MT group exhibited a relatively smooth cartilage surface, modest chondrocyte loss, mild synovial hyperplasia, and increased subchondral bone thickness. ICH results showed that MT downregulated the expression of components related to matrix degradation. ELISA results showed that MT reduced serum inflammatory cytokine levels. In vitro experiments confirmed that MT upregulated the expression of SIRT1/Nrf2/TGF-ß/BMPs while inhibiting the NF-κB pathway and matrix degradation-related components. The introduction of the SIRT1 inhibitor Selisistat (EX527) reversed the effects of MT. Together, these findings suggest that MT has the potential to ameliorate inflammation, inhibit the release of matrix-degrading enzymes, and improve the cartilage condition. This study provides a new theoretical basis for understanding the role of MT in decelerating cartilage degradation and promoting chondrocyte repair in in vivo and in vitro cultured chondrocytes.
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Cartílago Articular , Condrocitos , Melatonina , Factor 2 Relacionado con NF-E2 , FN-kappa B , Transducción de Señal , Sirtuina 1 , Factor de Crecimiento Transformador beta , Animales , Sirtuina 1/metabolismo , Sirtuina 1/genética , Factor 2 Relacionado con NF-E2/metabolismo , Melatonina/farmacología , FN-kappa B/metabolismo , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/patología , Transducción de Señal/efectos de los fármacos , Cartílago Articular/metabolismo , Cartílago Articular/patología , Cartílago Articular/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismo , Masculino , Matriz Extracelular/metabolismo , Inflamación/metabolismo , Inflamación/patologíaRESUMEN
Parkinson's disease (PD) is a common neurodegenerative disorder with a prolonged prodromal phase. Higher urinary bis(monoacylglycerol)phosphate (BMP) levels associate with LRRK2 (leucine-rich repeat kinase 2) and GBA1 (glucocerebrosidase) mutations, and are considered as potential noninvasive biomarkers for predicting those mutations and PD progression. However, their reliability has been questioned, with inadequately investigated genetics, cohorts, and population. In this study, multiple statistical hypothesis tests were employed on urinary BMP levels and sequences of 90 PD-risk single nucleotide polymorphisms (SNPs) from Parkinson's Progression Markers Institution (PPMI) participants. Those SNPs were categorized into four groups based on their impact on BMP levels in various cohorts. Variants rs34637584 G/A and rs34637584 A/A (LRRK2 G2019S) were identified as the most relevant on increasing urinary BMP levels in the PD cohort. Meanwhile, rs76763715 T/T (GBA1) was the primary factor elevating BMP levels in the prodromal cohort compared to its T/C and C/C variants (N370S) and the PD cohort. Proteomics analysis indicated the changed transport pathways may be the reasons for elevated BMP levels in prodromal patients. Our findings demonstrated that higher urinary BMP levels alone were not reliable biomarkers for PD progression or gene mutations but might serve as supplementary indicators for early diagnosis and treatment.
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Lisofosfolípidos , Monoglicéridos , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados , Mutación , BiomarcadoresRESUMEN
Urban stormwater runoff is a significant source of nutrient pollution that is very costly to treat. Water quality trading (WQT) is a market-based strategy that can be used to lower the costs associated with meeting stormwater quality regulations. While many WQT programs have experienced low participation, Virginia's program has seen high participation due to the inclusion of land developers and other regulated stormwater dischargers. However, the extent to which WQT is used as a compliance option by regulated stormwater dischargers is not well understood, particularly when compared with the adoption of traditional compliance options. To address this knowledge gap, we collated a novel dataset comprising site characteristics and stormwater compliance methods for all development projects in the City of Roanoke, Virginia from December 2015 to March 2022. We analyzed this dataset to characterize the adoption of nutrient offset credits and other compliance methods being used, including best management practices (BMPs) and improved land covers associated with reduced nutrient export. Results show that credits are the preferred compliance option in Roanoke and were used as the only treatment compliance method for 59% of projects with treatment requirements. Projects using credits corresponded with a lower median disturbed area (1.36 acres) and lower median nutrient load reduction requirement (0.69 pounds of total phosphorus per year) compared with other compliance methods. Furthermore, we found that 58% of the projects that used credits achieved stormwater quantity compliance using methods other than implementing stormwater control devices. By mapping buyers and sellers of credits, we found that all credit sellers are downstream of the development projects. We discuss how this downstream trading could be a cause for concern, as part of a larger discussion of the advantages of tracking stormwater compliance methods, drawing on Roanoke as a case study.
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Contaminantes Químicos del Agua , Calidad del Agua , Virginia , Lluvia , Ciudades , Fósforo/análisis , Movimientos del Agua , Monitoreo del Ambiente/métodosRESUMEN
Agricultural nutrients nitrogen and phosphorus can subsequently be transported to waterways and are often managed through the adoption of best management practices (BMPs). However, we have a poor understanding of how the use of BMPs varies spatially and how BMP adoption might be related to nutrient yields in surface waters. To address this, we performed a survey of agricultural landowners across New York State and compared this with estimates of annual incremental nitrogen and phosphorus yields of agricultural origin from the Spatially Referenced Regressions On Watershed attributes (SPARROW) model. Using these socio-behavioral data and SPARROW predictions, we perform colocation analysis to identify areas where watersheds with high nutrient yield from agriculture are collocated with non-use of agricultural BMPs. This colocation analysis offers a novel methodology for identifying areas where monitoring of waterways and promotion of best management practices could be targeted to achieve the greatest benefits.
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Promoting conservation on rented farmland is a challenge for stakeholders working with non-operating landowners (NOLs) and tenant farmers (operators). We conducted an online survey to identify stakeholders who engage with NOLs, and understand how their positioning as 'intermediaries' could be leveraged to help bridge the NOL-operator communication gap. A majority of identified stakeholders/intermediaries worked in government agencies, university extension, law firms, or farm management companies. Intermediaries believed that NOLs trusted them for several conservation activities, however, they believed that NOLs were more influenced by operators than by intermediaries. The message that engaging in conservation can help preserve the farm for future generation was perceived to be influential in motivating NOLs. Our findings suggest the need for a holistic approach to engage NOLs by accounting for trust in and influence of intermediaries and operators, and the salience of conservation messages and messaging when promoting conservation behaviors on rented farmlands.
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Conservación de los Recursos Naturales , Agricultores , Humanos , Granjas , Encuestas y Cuestionarios , Comunicación , AgriculturaRESUMEN
Identifying vulnerable areas to erosion within the watershed and implementing best management practices (BMPs) are crucial steps in mitigating watershed degradation by minimizing sediment yields. The present study evaluates and identifies the BMPs in the Seybouse basin, northeastern Algeria, using the Soil and Water Assessment Tool (SWAT) model. After successful calibration and validation, the model demonstrated a satisfactory ability to simulate monthly discharge and sediment. Then, the calibrated model was employed to evaluate the efficacy of diverse management practices in sediment control. In the SWAT, three soil and conservation practices, as well as vegetated filter strips (VFSs), grade stabilization structures (GSSs), and terracing were evaluated. The average annual sediment yield in the Seybouse watershed is determined to be 14.43 t/ha year, constituting 71% of the total soil loss. VFS demonstrated a sediment reduction of 37.30%, GSS 20.40%, and terracing 42.30%. Among these strategies, terracing results in the greatest reduction, followed by VFS. The results of this study area can be useful for informed decision-making regarding optimal watershed management strategies.
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Monitoreo del Ambiente , Sedimentos Geológicos , Sedimentos Geológicos/química , Ríos , Argelia , Modelos Teóricos , Suelo , AguaRESUMEN
Craniofacial anomalies (CFAs) are a diverse group of disorders affecting the shapes of the face and the head. Malformation of the cranial base in humans leads CFAs, such as midfacial hypoplasia and craniosynostosis. These patients have significant burdens associated with breathing, speaking, and chewing. Invasive surgical intervention is the current primary option to correct these structural deficiencies. Understanding molecular cellular mechanism for craniofacial development would provide novel therapeutic options for CFAs. In this study, we found that enhanced bone morphogenetic protein (BMP) signaling in cranial neural crest cells (NCCs) (P0-Cre;caBmpr1a mice) causes premature fusion of intersphenoid synchondrosis (ISS) resulting in leading to short snouts and hypertelorism. Histological analyses revealed reduction of proliferation and higher cell death in ISS at postnatal day 3. We demonstrated to prevent the premature fusion of ISS in P0-Cre;caBmpr1a mice by injecting a p53 inhibitor Pifithrin-α to the pregnant mother from E15.5 to E18.5, resulting in rescue from short snouts and hypertelorism. We further demonstrated to prevent premature fusion of cranial sutures in P0-Cre;caBmpr1a mice by injecting Pifithrin-α through E8.5 to E18.5. These results suggested that enhanced BMP-p53-induced cell death in cranial NCCs causes premature fusion of ISS and sutures in time-dependent manner.
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Anomalías Craneofaciales , Base del Cráneo , Proteínas Morfogenéticas Óseas/metabolismo , Cresta Neural/metabolismo , Cresta Neural/patología , Proliferación Celular , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/metabolismo , Masculino , Femenino , Animales , Ratones , Animales Recién Nacidos , Transducción de Señal , Apoptosis , Condrocitos/metabolismo , Proteínas Smad/metabolismo , Unión Proteica , Anomalías Craneofaciales/metabolismo , Anomalías Craneofaciales/patología , Embarazo , Base del Cráneo/anomalías , Base del Cráneo/metabolismo , Base del Cráneo/patología , Hipertelorismo/metabolismo , Hipertelorismo/patologíaRESUMEN
The growth and evolutionary expansion of the cerebral cortex are defined by the spatial-temporal production of neurons, which itself depends on the decision of radial glial cells (RGCs) to self-amplify or to switch to neurogenic divisions. The mechanisms regulating these RGC fate decisions are still incompletely understood. Here, we describe a novel and evolutionarily conserved role of the canonical BMP transcription factors SMAD1/5 in controlling neurogenesis and growth during corticogenesis. Reducing the expression of both SMAD1 and SMAD5 in neural progenitors at early mouse cortical development caused microcephaly and an increased production of early-born cortical neurons at the expense of late-born ones, which correlated with the premature differentiation and depletion of the pool of cortical progenitors. Gain- and loss-of-function experiments performed during early cortical neurogenesis in the chick revealed that SMAD1/5 activity supports self-amplifying RGC divisions and restrains the neurogenic ones. Furthermore, we demonstrate that SMAD1/5 stimulate RGC self-amplification through the positive post-transcriptional regulation of the Hippo signalling effector YAP. We anticipate this SMAD1/5-YAP signalling module to be fundamental in controlling growth and evolution of the amniote cerebral cortex.
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Corteza Cerebral/metabolismo , Células-Madre Neurales/metabolismo , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Proteínas Morfogenéticas Óseas/genética , Proteínas Morfogenéticas Óseas/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Corteza Cerebral/embriología , Células Ependimogliales/citología , Células Ependimogliales/metabolismo , Femenino , Ratones , Neurogénesis/genética , Neurogénesis/fisiología , Transducción de Señal/fisiología , Proteína Smad1/genética , Proteína Smad5/genética , Proteínas Señalizadoras YAPRESUMEN
BACKGROUND: This study aimed to get a deeper insight into new osteosarcoma (OS) signature based on bone morphogenetic proteins (BMPs)-related genes and to confirm the prognostic pattern to speculate on the overall survival among OS patients. METHODS: Firstly, pathway analyses using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were managed to search for possible prognostic mechanisms attached to the OS-specific differentially expressed BMPs-related genes (DEBRGs). Secondly, univariate and multivariate Cox analysis was executed to filter the prognostic DEBRGs and establish the polygenic model for risk prediction in OS patients with the least absolute shrinkage and selection operator (LASSO) regression analysis. The receiver operating characteristic (ROC) curve weighed the model's accuracy. Thirdly, the GEO database (GSE21257) was operated for independent validation. The nomogram was initiated using multivariable Cox regression. Immune infiltration of the OS sample was calculated. Finally, the three discovered hallmark genes' mRNA and protein expressions were verified. RESULTS: A total of 46 DEBRGs were found in the OS and control samples, and three prognostic DEBRGs (DLX2, TERT, and EVX1) were screened under the LASSO regression analyses. Multivariate and univariate Cox regression analysis were devised to forge the OS risk model. Both the TARGET training and validation sets indicated that the prognostic biomarker-based risk score model performed well based on ROC curves. In high- and low-risk groups, immune cells, including memory B, activated mast, resting mast, plasma, and activated memory CD4 + T cells, and the immune, stromal, and ESTIMATE scores showed significant differences. The nomogram that predicts survival was established with good performance according to clinical features of OS patients and risk scores. Finally, the expression of three crucial BMP-related genes in OS cell lines was investigated using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB). CONCLUSION: The new BMP-related prognostic signature linked to OS can be a new tool to identify biomarkers to detect the disease early and a potential candidate to better treat OS in the future.
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Neoplasias Óseas , Osteosarcoma , Humanos , Pronóstico , Nomogramas , Western BlottingRESUMEN
Endothelial cells in veins differ in morphology, function and gene expression from those in arteries and lymphatics. Understanding how venous and arterial identities are induced during development is required to understand how arterio-venous malformations occur, and to improve the outcome of vein grafts in surgery by promoting arterialization of veins. To identify factors that promote venous endothelial cell fate in vivo, we isolated veins from quail embryos, at different developmental stages, that were grafted into the coelom of chick embryos. Endothelial cells migrated out from the grafted vein and their colonization of host veins and/or arteries was quantified. We show that venous fate is promoted by sympathetic vessel innervation at embryonic day 11. Removal of sympathetic innervation decreased vein colonization, while norepinephrine enhanced venous colonization. BMP treatment or inhibition of ERK enhanced venous fate, revealing environmental neurotransmitter and BMP signaling and intrinsic ERK inhibition as actors in venous fate acquisition. We also identify the BMP antagonist Noggin as a potent mediator of venous arterialization.
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Células Endoteliales , Venas , Animales , Arterias , Diferenciación Celular/fisiología , Embrión de Pollo , Transducción de Señal , Venas/metabolismoRESUMEN
OBJECTIVE: To investigate whether the Anti-Müllerian Hormone (AMH), an ovarian hormone belonging to the Transforming Growth Factor ß superfamily, may represent a possible candidate for use as a bone anabolic factor. METHODS: We performed in vitro studies on Human Osteoblasts (HOb) to evaluate the expression and the functionality of AMHRII, the AMH receptor type-2, and investigate the effects of exogenous AMH exposure on osteogenic gene expression and osteoblast functions. RESULTS: We reported the first evidence for the expression and functionality of AMHRII in HOb cells, thus suggesting that osteoblasts may represent a specific target for exogenous AMH treatment. Furthermore, the exposure to AMH exerted a stimulatory effect on HOb cells leading to the activation of osteogenic genes, including the upregulation of osteoblastic transcription factors such as RUNX and OSX, along with increased deposition of mineralized nodules. CONCLUSION: Our findings proved interesting clues on the stimulatory effects of AMH on mature osteoblasts expressing its specific receptor, AMHRII. This study may therefore have translation value in opening the perspective that AMH may be an effective candidate to counteract the bone loss in osteoporotic patients by selectively targeting osteoblast with minimal off-target effect.
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Hormona Antimülleriana , Hormonas Peptídicas , Humanos , Hormona Antimülleriana/farmacología , Diferenciación Celular , Expresión Génica , Osteoblastos/metabolismo , Receptores de Péptidos/genética , Receptores de Péptidos/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/genética , Factor de Crecimiento Transformador beta/genéticaRESUMEN
MicroRNAs (miRNAs) are a family of small, single-stranded, and non-protein coding RNAs about 19 to 22 nucleotides in length, that have been reported to have important roles in the control of bone development. MiRNAs have a strong influence on osteoblast differentiation through stages of lineage commitment and maturation, as well as via controlling the activities of osteogenic signal transduction pathways. Generally, miRNAs may modulate cell stemness, proliferation, differentiation, and apoptosis by binding the 3'-untranslated regions (3'-UTRs) of the target genes, which then can subsequently undergo messenger RNA (mRNA) degradation or protein translational repression. MiRNAs manage the gene expression in osteogenic differentiation by regulating multiple signalling cascades and essential transcription factors, including the transforming growth factor-beta (TGF-ß)/bone morphogenic protein (BMP), Wingless/Int-1(Wnt)/ß-catenin, Notch, and Hedgehog signalling pathways; the Runt-related transcription factor 2 (RUNX2); and osterix (Osx). This shows that miRNAs are essential in regulating diverse osteoblast cell functions. TGF-ßs and BMPs transduce signals and exert diverse functions in osteoblastogenesis, skeletal development and bone formation, bone homeostasis, and diseases. Herein, we highlighted the current state of in vitro and in vivo research describing miRNA regulation on the canonical TGF-ß/BMP signalling, their effects on osteoblast linage, and understand their mechanism of action for the development of possible therapeutics. In this review, particular attention and comprehensive database searches are focused on related works published between the years 2000 to 2022, using the resources from PubMed, Google Scholar, Scopus, and Web of Science.
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MicroARNs , Factor de Crecimiento Transformador beta , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Osteogénesis/genética , Proteínas Hedgehog/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Diferenciación Celular/genética , Transducción de Señal , Osteoblastos/metabolismoRESUMEN
Increased funding and resources have become available in recent years for agricultural producers to plant cover crops to improve soil health and prevent nutrient loss and erosion; however, cover crop adoption remains relatively low and has been uneven across different Midwestern counties. This study employed a controlled comparison method to investigate the social factors affecting cover crop adoption in Iowa, Illinois, and Indiana. In each state, the authors compared pairs of neighboring counties, where one county was a relatively higher adopter and the other was a lower adopter of cover crops, while controlling for variations in climate conditions. Results show that there were multiple factors explaining the difference in cover crop adoption among county pairs. Social factors included attitudes toward cover crops; conservation agency influence; presence of cover crop experts, advocates, and/or entrepreneurs; and collaboration between agencies and the private sector. Other important factors included topography, cattle raising, organic production, and local incentive-based programs. Among these, collaborations between agencies and the private sector played the most important role in explaining why some counties had higher rates of cover crop adoption compared to their neighbors.
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Factores Sociales , Suelo , Animales , Bovinos , Agricultura/métodos , Productos Agrícolas , ClimaRESUMEN
Using the US EPA's Grants Reporting and Tracking System (GRTS), we test if completion of best management practices (BMPs) through the Clean Water Act Section (§)319 National Nonpoint Source Program was associated with a decreasing trend in total suspended solids (TSS) load (metric tons/year). The study area chosen had 21 completed projects in the Cuyahoga River watershed in northeastern Ohio from 2000 to 2018. The §319 projects ranged from dam removal, floodplain/wetland restoration to stormwater projects. There was an overall decreasing trend in TSS loads. We identified three phases of project implementation and completion, where phase 1 had ongoing projects, but none completed (2000-2004). The steepest decrease in loads, identified as phase 2 (2005-2011), was associated with completion of low-head dam modification and removal projects on the mainstem of the Cuyahoga River. A likely decreasing trend was associated with projects completed in the tributaries, such as natural channel design restoration and stormwater green infrastructure (phase 3). Pairing sediment reduction estimates from projects with the river's flow normalized TSS loading trend, we estimated that the §319 effort may account for a small fraction of the TSS load reduction. Other stream restoration projects (non-§319) have also been done in the Cuyahoga watershed by other organizations. However, trying to compile these other projects is challenging in larger watersheds having multiple municipalities, agencies, and nonprofits doing restoration without better coordinated record keeping and monitoring. While a decreasing trend in a pollutant load is a desirable water quality outcome, determining what contributed to that trend remains difficult.
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This study conducted a spatio-temporal analysis of runoff, total suspended sediment, suspended particulate carbon, nitrogen, and phosphorus loadings within the 2.06 km2 Steppler subwatershed in southern Manitoba of Canada based on 11 years of field monitoring data collected at nine stations. Results showed that the nutrient losses were very small because of the implementation of multiple BMPs in the study area. However, a high spatio-temporal variation of runoff and water quality parameters was found for the nine fields within the subwatershed. The average runoff coefficient was 0.19 at the subwatershed outlet with sediment, suspended particulate carbon, total nitrogen, and total phosphorus losses of 73.8, 6.10, 4.54, and 0.76 kg/ha respectively. Spring snowmelt runoff was about 74.5% of the annual runoff at the subwatershed outlet, while for sediment, suspended particulate carbon, total nitrogen, and total phosphorus, the proportions were 61.1%, 63.6%, 74.9%, and 81.2% respectively during the monitoring period, which suggests that BMPs designed for reducing nutrient loadings from snowmelt runoff would be more effective than BMPs designed for reducing pollutant loading from rainfall storms in the study area. Research findings from this study will benefit the enhancement of current BMPs and the development of new BMPs in the region to minimize soil and nutrient losses from agricultural fields and improve water quality in receiving water bodies.
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Conservación de los Recursos Naturales , Monitoreo del Ambiente , Canadá , Conservación de los Recursos Naturales/métodos , Pradera , Movimientos del Agua , Fósforo/análisis , Nitrógeno/análisis , Nutrientes , Agricultura/métodosRESUMEN
Excess loading of nitrogen and phosphorus to river networks causes environmental harm, but reducing loads from large river basins is difficult and expensive. We develop a new tool, the River Basin Export Reduction Optimization Support Tool (RBEROST) to identify least-cost combinations of management practices that will reduce nutrient loading to target levels in downstream and mid-network waterbodies. We demonstrate the utility of the tool in a case study in the Upper Connecticut River basin in New England, USA. The total project cost of optimized lowest-cost plans ranged from $18.0 million to $41.0 million per year over 15 years depending on user specifications. Plans include both point source and non-point source management practices, and most costs are associated with urban stormwater practices. Adding a 2% margin of safety to loading targets improved estimated probability of success from 37.5% to 99%. The large spatial scale of RBEROST, and the consideration of both point and non-point source contributions of nutrients, makes it well suited as an initial screening tool in watershed planning.
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Adipose tissues, including white, beige, and brown adipose tissue, have evolved to be highly dynamic organs. Adipose tissues undergo profound changes during development and regeneration and readily undergo remodeling to meet the demands of an everchanging metabolic landscape. The dynamics are determined by the high plasticity of adipose tissues, which contain various cell types: adipocytes, immune cells, endothelial cells, nerves, and fibroblasts. There are numerous proteins that participate in regulating the plasticity of adipose tissues. Among these, bone morphogenetic proteins (BMPs) were initially found to regulate the differentiation of adipocytes, and they are being reported to have pleiotropic functions by emerging studies. Here, in the first half of the article, we summarize the plasticity of adipocytes and macrophages, which are two groups of cells targeted by BMP signaling in adipose tissues. We then review how BMPs regulate the differentiation, death, and lipid metabolism of adipocytes. In addition, the potential role of BMPs in regulating adipose tissue macrophages is considered. Finally, the expression of BMPs in adipose tissues and their metabolic relevance are discussed.
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Tejido Adiposo/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Transducción de Señal , Adipocitos/citología , Adipocitos/metabolismo , Animales , Muerte Celular , Diferenciación Celular , Senescencia Celular , Humanos , Macrófagos/citología , Transcripción GenéticaRESUMEN
Glioblastomas are the most prevalent and lethal primary brain tumor and are comprised of hierarchies with self-renewing cancer stem cells (CSCs) at the apex. Like neural stem cells (NSCs), CSCs reside in functional niches that provide essential cues to maintain the cellular hierarchy. Bone morphogenetic proteins (BMPs) instruct NSCs to adopt an astrocyte fate and are proposed as anti-CSC therapies to induce differentiation, but, paradoxically, tumors express high levels of BMPs. Here we demonstrate that the BMP antagonist Gremlin1 is specifically expressed by CSCs as protection from endogenous BMPs. Gremlin1 colocalizes with CSCs in vitro and in vivo. Furthermore, Gremlin1 blocks prodifferentiation effects of BMPs, and overexpression of Gremlin1 in non-CSCs decreases their endogenous BMP signaling to promote stem-like features. Consequently, Gremlin1-overexpressing cells display increased growth and tumor formation abilities. Targeting Gremlin1 in CSCs results in impaired growth and self-renewal. Transcriptional profiling demonstrated that Gremlin1 effects were associated with inhibition of p21(WAF1/CIP1), a key CSC signaling node. This study establishes CSC-derived Gremlin1 as a driving force in maintaining glioblastoma tumor proliferation and glioblastoma hierarchies through the modulation of endogenous prodifferentiation signals.
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Glioma/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Células Madre Neoplásicas/metabolismo , Animales , Proteína Morfogenética Ósea 2/metabolismo , Ciclo Celular/genética , Proliferación Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Glioma/genética , Glioma/patología , Xenoinjertos , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Células Madre Neoplásicas/patología , Transducción de SeñalRESUMEN
Conservation practices (CPs) are integral to maintaining the long-term viability of agro-ecological systems. Because farming systems and farmers' values and attitudes are heterogeneous, factors that consistently predict conservation behaviors remain elusive. Moreover, heterogeneity is present among studies regarding the type of CPs examined, and whether behavioral intentions or actual behaviors were measured. This study considers the characteristics of each CP, and whether a given study measured behavioral intention or actual behavior, to better understand farmers' adoption of CPs. We reviewed and analyzed 35 years (1982-2017) of quantitative conservation adoption literature in the United States. We categorized CPs based on their primary purpose, the type of benefit they provide, and whether they are operational or structural. We also examined the following five CPs: conservation tillage, buffers or borders, soil testing, grassed waterways, and cover crops. In our behavioral intention and actual behavior analysis, we found that attitudinal factors predicted both conservation intention and action (actual behavior), whereas current or previous use of practices only influenced actions, not stated conservation intentions. In our analysis focusing on CP characteristics, we found that having specific knowledge about and positive attitudes toward the CP, adoption of other CPs, seeking and using information, larger farm size, and vulnerable land predicted actual adoption across nearly all CP categorizations. Nuances emerge when comparing predictors of CPs that share a particular characteristic. For example, we found farm characteristics to be comparatively more important in predicting adoption of soil management CPs than nutrient and livestock management CPs, and farmers' stewardship identity to be more important for permanent practices than operational practices.
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Agricultura , Intención , Estados Unidos , Humanos , Encuestas y Cuestionarios , Agricultores , SueloRESUMEN
In the upper Midwestern United States, one of the central goals of agri-environmental policy is to reduce environmental and water quality degradation resulting from agriculture without sacrificing production. The primary tool available to policymakers is offering farmers incentives to voluntarily adopt more conservation practices, often known as Best Management Practices (BMPs). Using the Theory of Planned Behavior (TPB) and Diffusion of Innovation (DoI) frameworks, we surveyed 2000 agricultural landowners in the Minnesota River Basin to explore the socio-psychological drivers of the adoption decisions for specific BMPs such as wetlands, cover crops, and nutrient management. We found that attitude (both favorable and unfavorable), awareness of environmental problems, and appreciation of ecosystem services significantly affected landowners' adoption intentions for the three BMPs. We applied landowner segmentation analysis and compared both the socio-psychological and socio-demographic features among different landowner segments (i.e. environmentally-conscious landowners, engaging-absentee landowners, and adoption-averse landowners). Our study can inform the development of targeted conservation policies for various landowner types to motivate BMPs adoption.