725 research outputs found

    Surviving a Reclamation Project: Shifting Fisherfolk Provisioning Strategies in a Metropolitan City

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    Development has often been equated with modernization and urbanization, as reflected in government development programs such as the Cebu Integrated Area Development Master Plan (CIADMP). One of the flagship projects under the CIADMP is the 330.9-hectare Cebu South Reclamation Project (CSRP) formulated by foreign consultants, local government authorities, and the business sector. Underlying these indicators of economic development that encourage such projects, urban fishing communities have been uprooted from their livelihoods that are reliant on the sea subsequently reclaimed by the project. This study focuses on how the affected fisherfolk in Cebu City changed their household provisioning strategies as a result of the CSRP. The study primarily utilized ethnographic research methodologies, including key informant interviews, focus group discussions, deep hanging out, and field observation. Newspaper research and secondary data analysis were likewise done to supplement field data. Findings are based on the narratives of the affected residents, which show that prior to the CSRP, primary livelihood strategies of most residents revolved around small-scale fishing practices: panawom (diving/spear fishing), pamasol (hook and line fishing), pamukot (fishing using mesh nets), panginhas (gleaning), and panu (gathering shrimps and crabs at low tide). The implementation of the CSRP has adversely affected their livelihood, leading them to shift to less lucrative and mostly informal, irregular, temporary service-related work. Strategies employed were not only in terms of livelihood options but also in tapping social networks, pooling resources, cutting on consumption costs, and joining resistance movements

    RNF168 cooperates with RNF8 to mediate FOXM1 ubiquitination and degradation in breast cancer epirubicin treatment

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    The forkhead box M1 (FOXM1) transcription factor has a central role in genotoxic agent response in breast cancer. FOXM1 is regulated at the post-translational level upon DNA damage, but the key mechanism involved remained enigmatic. RNF168 is a ubiquitination E3-ligase involved in DNA damage response. Western blot and gene promoter-reporter analyses showed that the expression level and transcriptional activity of FOXM1 reduced upon RNF168 overexpression and increased with RNF168 depletion by siRNA, suggesting that RNF168 negatively regulates FOXM1 expression. Co-immunoprecipitation studies in MCF-7 cells revealed that RNF168 interacted with FOXM1 and that upon epirubicin treatment FOXM1 downregulation was associated with an increase in RNF168 binding and conjugation to the protein degradation-associated K48-linked polyubiquitin chains. Consistently, RNF168 overexpression resulted in an increase in turnover of FOXM1 in MCF-7 cells treated with the protein synthesis inhibitor cycloheximide. Conversely, RNF168, knockdown significantly enhanced the half-life of FOXM1 in both absence and presence of epirubicin. Using a SUMOylation-defective FOXM1-5x(K>R) mutant, we demonstrated that SUMOylation is required for the recruitment of RNF168 to mediate FOXM1 degradation. In addition, clonogenic assays also showed that RNF168 mediates epirubicin action through targeting FOXM1, as RNF168 could synergise with epirubicin to repress clonal formation in wild-type but not in FOXM1-deficient mouse embryo fibroblasts (MEFs). The physiological relevance of RNF168-mediated FOXM1 repression is further emphasized by the significant inverse correlation between FOXM1 and RNF168 expression in breast cancer patient samples. Moreover, we also obtained evidence that RNF8 recruits RNF168 to FOXM1 upon epirubicin treatment and cooperates with RNF168 to catalyse FOXM1 ubiquitination and degradation. Collectively, these data suggest that RNF168 cooperates with RNF8 to mediate the ubiquitination and degradation of SUMOylated FOXM1 in breast cancer genotoxic response

    FOXM1 recruits nuclear Aurora kinase A (AURKA) to participate in a positive feedback loop essential for the self-renewal of breast cancer stem cells

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    Substantial evidence suggests that breast cancer initiation, recurrence and drug resistance is supported by breast cancer stem cells (BCSCs). Recently, we reported a novel role of Aurora kinase A (AURKA) in BCSCs, as a transactivating co-factor in the induction of the c-Myc oncoprotein. However, the mode of action and transcriptional network of nuclear AURKA in BCSCs remain unknown. Here, we report that nuclear AURKA can be recruited by FOXM1 as a co-factor to transactivate FOXM1-target genes in a kinase-independent manner. In addition, we show that AURKA and FOXM1 participate in a tightly coupled positive feedback loop to enhance BCSC phenotype. Indeed, kinase-dead AURKA can effectively transactivate the FOXM1 promoter through a Forkhead response element (FKHR), while FOXM1 can activate AURKA expression at the transcriptional level in a similar manner. Consistently, breast cancer patient samples portrayed a strong and significant correlation between the expression levels of FOXM1 and AURKA. Moreover, both FOXM1 and AURKA were essential for maintaining the BCSC population. Finally, we demonstrated that the Aurora kinase A inhibitor AKI603 and FOXM1 inhibitor thiostrepton acted synergistically to inhibit cytoplasmic Aurora kinase A activity and disrupt the nuclear AURKA/FOXM1 positive feedback loop respectively, resulting in a more effective inhibition of the tumorigenicity and self-renewal ability of BCSCs. Collectively, our study uncovers a previously unknown tightly coupled positive feedback signalling loop between AURKA and FOXM1, crucial for BCSC self-renewal. Remarkably, our data reveals a novel potential therapeutic strategy for targeting both the cytoplasmic and nuclear AURKA function to effectively eliminate BCSCs, so as to overcome both breast cancer and drug resistance

    Anti-COVID vaccination for adolescents: A survey on determinants of vaccine parental hesitancy

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    Vaccine hesitancy has been considered one of the most severe threats to global health, as it represents an obstacle to achieving adequate vaccination coverage. Recent research studies aimed at investigating the propensity for anti-COVID vaccination among adults have found a high prevalence of vaccine hesitancy, but few data are available on parental vaccine hesitancy. We therefore built an anonymous online survey to investigate the factors related to the vaccine hesitancy of parents of adolescents between 12 and 17 years of age, with a special focus on demographic factors and the domains of confidence and complacency. The online survey was conducted by using the Crowd Signal platform from 15 July to 16 August 2021, in Italy. A total of 1799 analyzable questionnaires were analyzed. Overall, Favorable and Doubtful parents declared a higher level of confidence on safety and efficacy of pediatric vaccines and on confidence in health institutions than Hesitant/Reluctant ones (p-values < 0.001). The univariate multinomial logistic regression analysis and the multivariate multinomial logistic regression analysis showed that the Hesitant/Reluctant parents were younger than 40 years of age, with a secondary-school or three-year degree, free-lance, with a family income below €28,000, with an erroneous perception of the risk of COVID-19 as disease and with fear of anti-COVID vaccination. These results, which should be confirmed in a larger population and in different geographical areas, should lead Institutions and stakeholders to identify targeted communication tools to improve trust in health institutions, especially by younger parents

    Functionally graded plate fracture analysis using the field boundary element method

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    This paper describes the Field Boundary Element Method (FBEM) applied to the fracture analysis of a 2D rectangular plate made of Functionally Graded Material (FGM) to calculate Mode I Stress Intensity Factor (SIF). The case study of this Field Boundary Element Method is the transversely isotropic plane plate. Its material presents an exponential variation of the elasticity tensor depending on a scalar function of position, i.e., the elastic tensor results from multiplying a scalar function by a constant taken as a reference. Several examples using a parametric representation of the structural response show the suitability of the method that constitutes a Stress Intensity Factor evaluation of Functionally Graded Materials plane plates even in the case of more complex geometries

    Regulation of PERK expression by FOXO3: a vulnerability of drug-resistant cancer cells

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    The major impediment to effective cancer therapy has been the development of drug resistance. The tumour suppressive transcription factor FOXO3 promotes cell cycle arrest, senescence and cell death, and mediates the cytotoxic and cytostatic functions of cancer therapeutics. In consequence, FOXO3 is often downregulated as an adaptive response in cancer and particularly in chemotherapeutic drug-resistant cells. Consistently, we find that FOXO3 expression is attenuated in the drug-resistant MCF-7-EpiR and MCF-7-TaxR compared to the parental MCF-7 breast cancer cells. Using ChIP, short-interfering RNA (siRNA) knockdown, and overexpression assays as well as Foxo1/3/4−/− MEFs, we establish the endoplasmic reticulum (ER)-stress defence modulator PERK (eIF2AK3) as a direct downstream transcriptional target of FOXO3. In agreement, there is also a positive correlation between FOXO3 and PERK expression at the protein and RNA levels in breast cancer patient samples. We uncover that PERK expression is downregulated but its activity constitutively elevated in the drug-resistant cells. With this in mind, we exploit this adaptive response of low FOXO3 and PERK expression, and high PERK activity in drug-resistant breast cancer cells and show that these drug-resistant cells are specifically sensitive to PERK inhibition. In support of this finding, we show that ectopic overexpression of FOXO3 can reduce the sensitivity of the resistant cells to the PERK inhibitor GSK2606414, while the Foxo1/3/4−/− MEFs expressing lower levels of PERK are more sensitive to PERK inhibition compared to wild-type MEFs. PERK inhibitor-titration and -time course experiments showed that the drug-resistant cells, which express lower expression and higher activity levels of PERK, are more sensitive to the increasing concentrations of PERK inhibitor compared to parental MCF-7 cells. Our present work thus reveals a chemotherapeutic drug-resistant cancer cell vulnerability in PERK and suggests PERK as a potential target for cancer therapy, specifically in the context of drug-resistant cancers

    Hypertriglyceridemic waist identifies HIV+ men and women at increased cardiometabolic risk

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    Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) is an inexpensive approach to identify patients at risk of coronary artery disease in apparently healthy individuals who may be at increased risk of type 2 diabetes and coronary heart disease because of an excess of intra-abdominal (visceral) fat. We examined the ralationship between the hypertriglyceridemic-waist and selected cardiometabolic risk factors in HIV individuals

    Menentukan Koefisien Ekspansi Linier Batang Kuningan Dengan Teknik Espi (Electronic Speckle Pattern Interferometry)

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    Telah dilakukan eksperimen untuk menentukan koefisien ekspansi linier batang kuningan dengan teknik ESPI (Electronic Speckle Pattern Interferometry). Objek uji yang digunakan terbuat dari kuningan dengan diameter 45 mm, panjang 44 mm, dan dikenai beban thermal dari temperatur 30°Csampai dengan 40°C menggunakan heater (pemanas) yang ditempelkan erat dibelakang objek. Data citra spekel selama pemanasan diamati dan setiap selang waktu 1 menit disimpan di memori komputer untuk diproses. Pemrosesannya dilakukan dengan cara mensubtraksikan (mengurangkan) ke dua citraspekel pixel per pixel dan hasilnya ditampilkan di layar monitor dalam bentuk pola frinji. Dari eksperimen diperoleh harga koefisien ekspansi linier kuningan α = (1,96 ± 0,02)10-5/°C dengan standard deviasi terhadap rata-rata sebesar 1,02%.An experiment to determine the linear coefficient of expansion for the brass rod have been done by using the ESPI (Electronic Speckle Pattern Interferometry) technique. The specimen we used were brass with diameter 45 mm, length 44 mm, and thermal loaded from temperature 30°C up to 40°C use heaters behind object. The image speckle data for each 1 menit during thermal were record by the computers. Its process done by subtraction to image speckle data pixel by pixel, and the result presented on monitor screen in the fringe pattern. From experiment obtained that the average value of the linear coefficient of expansion for the brass is, α = (1,96 ± 0 ,02)10-5/°C with the deviation from average value is 1.02 %

    Environmental controls on ozone fluxes in a poplar plantation in Western Europe

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    Tropospheric O-3 is a strong oxidant that may affect vegetation and human health. Here we report on the O-3 fluxes from a poplar plantation in Belgium during one year. Surprisingly, the winter and autumn O-3 fluxes were of similar magnitude to ones observed during most of the peak vegetation development. Largest O-3 uptakes were recorded at the beginning of the growing season in correspondence to a minimum stomatal uptake. Wind speed was the most important control and explained 44% of the variability in the nighttime O-3 fluxes, suggesting that turbulent mixing and the mechanical destruction of O-3 played a substantial role in the O-3 fluxes. The stomatal O-3 uptake accounted for a seasonal average of 59% of the total O-3 uptake. Multiple regression and partial correlation analyses showed that net ecosystem exchange was not affected by the stomatal O-3 uptake. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved

    Impact of fertiliser, water table, and warming on celery yield and CO2 and CH4 emissions from fenland agricultural peat

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    Peatlands are globally important areas for carbon preservation; although covering only 3% of global land area, they store 30% of total soil carbon. Lowland peat soils can also be very productive for agriculture, but their cultivation requires drainage as most crops are intolerant of root-zone anoxia. This leads to the creation of oxic conditions in which organic matter becomes vulnerable to mineralisation. Given the demand for high quality agricultural land, 40% of the UK's peatlands have been drained for agricultural use. In this study we present the outcomes of a controlled environment experiment conducted on agricultural fen peat to examine possible trade-offs between celery growth (an economically important crop on the agricultural peatlands of eastern England) and emissions of greenhouse gases (carbon dioxide (CO2) and methane (CH4)) at different temperatures (ambient and ambient +5 °C), water table levels (−30 cm, and −50 cm below the surface), and fertiliser use. Raising the water table from −50 cm to −30 cm depressed yields of celery, and at the same time decreased the entire ecosystem CO2 loss by 31%. A 5 °C temperature increase enhanced ecosystem emissions of CO2 by 25% and increased celery dry shoot weight by 23% while not affecting the shoot fresh weight. Fertiliser addition increased both celery yields and soil respiration by 22%. Methane emissions were generally very low and not significantly different from zero. Our results suggest that increasing the water table can lower emissions of greenhouse gases and reduce the rate of peat wastage, but reduces the productivity of celery. If possible, the water table should be raised to −30 cm before and after cultivation, and only decreased during the growing season, as this would reduce the overall greenhouse gas emissions and peat loss, potentially not affecting the production of vegetable crops
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