Oxysterol binding to the extracellular domain of Smoothened in Hedgehog signaling

Oxysterols bind the seven-spanner transmembrane protein Smoothened and potently activate vertebrate Hedgehog signaling, a pathway essential in embryonic development, adult stem cell maintenance and cancer. It is unknown, however, if oxysterols are important for normal vertebrate Hedgehog signaling, and whether antagonizing oxysterols can inhibit the Hedgehog pathway. We developed azasterols that block Hedgehog signaling by binding the oxysterol-binding site of Smoothened. We show that the binding site for oxysterols and azasterols maps to the extracellular, cysteine-rich domain of Smoothened, and is completely separable from the site bound by other small molecule modulators, located within the heptahelical bundle of Smoothened. Smoothened mutants in which oxysterol binding is abolished no longer respond to oxysterols, and cannot be maximally activated by the Hedgehog ligand. Our results show that oxysterol binding to vertebrate Smoothened is required for normal Hedgehog signaling, and that targeting the oxysterol binding site is an effective strategy to inhibit Smoothened

Comparison of the performance of friction pendulums with uniform and variable radii

The paper presents research done by means of numerical simulation on a rigid structure isolated with friction pendulums. To this aim, we design friction pendulums which differ by the shape and dimension of the cylindrical sliding surface, respectively by the friction coefficients. Our target was to find out how the structure responds to a given excitation when the structure is equipped with diverse friction pendulums. A sinusoidal excitation with the frequency of 1 Hz is applied and the response in terms of displacements is captured. We found that the frequency of the structure does not change with the FP radius but the amplitude of the displacement is strongly dependent on this parameter. Because the circular and elliptical sections of the FP provide the structure with different natural frequencies, the resonance is achieved at other radii

Sustainable land management in mining areas in Serbia and Romania

The paper analyzes the impacts of mining activities on sustainable land management in mining areas in the Republic of Serbia and Romania and discusses the main challenges related to the management of these issues in legislation and practice. Particular attention is paid to land disturbance, mine waste management and land reclamation, as well as access to land for mining purposes, the transfer of mining royalties and the partnerships of the mining industry, governments, communities and civil society for sustainable mining. Both governments are willing to provide the adequate role to mining in strengthening the national economies, but they face numerous constraints in this matter. Sustainable mining practices and consistent implementation of the mining for the closure planning approach, within an improved legislative framework and in cooperation with stakeholders at all levels, create conditions for the development of creative, profitable, environmentally-sound and socially-responsible management and reuse of mine lands

Experimental setup to study two phase flows for environmental applications

The air water mix is a major concern for the environmental application. This paper proposes an experimental method to accede simultaneously at the water flow velocity field and at the void fraction. Instantaneous and mean fields, as well as the evolution with the flow parameters variation are obtained in cavitation or aerated flows. This method allows a good accuracy for the flow velocity fields (2%) and void (vapours or air) contours (4%)

Analysis of a low-voltage operating microgrid located in a residential area

The paper aims at providing the analysis of domestic energy generation and consumption within residential areas. The topic of this study is twofold: theoretical and experimental by addressing aspects related to the operation of a microgrid connected to the low-voltage distribution grid. In order to achieve the power quality analysis for various scenarios, an appropriate testing stand was developed by using the Chauvin Arnoux CA 8435 analyser. There is envisaged the modelling and design of a mixed microgrid characterized by two line sections established by three main energy consumption nodes. There have been integrated several connection points related to the distributed generation sources and to the photovoltaic power plants, respectively, and also several supply points for the household end-users. 13 operation scenarios have been developed and recorded by analysing the voltage variation within the microgrid. Furthermore, the paper envisages the stabilization impact of the microgrid voltage variation in the presence of distributed generation sources

Surgery of the colon; the impact of colostomy and postoperative complications on patients' quality of life

Introduction. This study aims to evaluate the impact of stoma formation on the quality of life of patients undergoing colonic surgery, considering both emergency and elective procedures. Several factors (demographic data, Charlson comorbidity score, type of surgical intervention, duration of hospitalization, postoperative outcomes and complications, etc.) were analyzed to understand their influence on patients' well-being. Materials and Methods. A retrospective analysis was performed on patients who underwent colorectal surgery that required stoma formation. A total of 270 patients were included in the study, with 69.25% undergoing emergency surgery and 30.74% undergoing elective procedures. Results. The Charlson comorbidity score was significantly higher in the emergency surgery group compared to the elective group, 8.51 vs 7.67, respectively (p < 0.05). Patients who underwent emergency surgery experienced more postoperative (including stoma-related) complications, leading to a lower quality of life score compared to those undergoing elective procedures. Conclusions. Especially in emergency cases, colostomy involves difficulties related to patient compliance and quality of life, a fact supported by higher scores regarding comorbidities and postoperative complications. Thus, presenting patients at early stages of disease, customized surgical techniques, and appropriate preoperative counseling can help improve both patient outcomes and overall well-being

International Asteroid Warning Network Timing Campaign : 2019 XS

Peer reviewe

The Marine Microbial Eukaryote Transcriptome Sequencing Project (MMETSP): illuminating the functional diversity of eukaryotic life in the oceans through transcriptome sequencing

International audienceCurrent sampling of genomic sequence data from eukaryotes is relatively poor, biased, and inadequate to address important questions about their biology, evolution, and ecology; this Community Page describes a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans

2023 DZ2 Planetary Defense Campaign

peer reviewedWe present the results of a fourth planetary defense exercise, focused this time on the small near-Earth asteroid (NEA) 2023 DZ2 and conducted during its close approach to the Earth in 2023 March. The International Asteroid Warning Network (IAWN), with support from NASA's Planetary Defense Coordination Office (PDCO), has been coordinating planetary defense observational campaigns since 2017 to test the operational readiness of the global planetary defense capabilities. The last campaign focused on the NEA Apophis, and an outcome of that exercise was the need for a short burst campaign to replicate a real-life near-Earth object impact hazard scenario. The goal of the 2023 DZ2 campaign was to characterize the small NEA as a potential impactor and exercise the planetary defense system including observations, hypothetical risk assessment and risk prediction, and hazard communication with a short notice of just 24 hr. The entire campaign lasted about 10 days. The campaign team was divided into several working groups based on the characterization method: photometry, spectroscopy, thermal IR photometry and optical polarimetry, radar, and risk assessment. Science results from the campaign show that 2023 DZ2 has a rotation period of 6.2745 ± 0.0030 minutes; visible wavelength color photometry/spectroscopy/polarimetry and near-IR spectroscopy all point to an E-type taxonomic classification with surface composition analogous to aubrite meteorites; and radar observations show that the object has a diameter of 30 ± 10 m, consistent with the high albedo (0.49) derived from polarimetric and thermal IR observations

POTENTIAL OF WINE TOURISM IN ROMANIA. CASE STUDY: DEALU MARE VINEYARD

Wine sector can contribute to the rediscovery of Romania as a possible tourist destination, and the multiplication of interest in this area can offer a wide range of experiences (through rural tourism, wine tourism), active holidays and even business opportunities. The development of tourist destinations is closely linked to their natural environment, cultural distinctiveness, social interaction, security and wellbeing of local populations. These characteristics make wine tourism the driving force for the conservation and development of the tourist destinations in the Dealu Mare vineyard, the largest vineyard in the most important wine-growing area of the country. Romania has a remarkable wine heritage, both on a European and global economic confirmed statistics every year. Wine tourism is on an incipient phase in Romania, compared to other countries with significant wine heritage, but is likely sufficiently sustained development, especially wine-growing potential value resulting from the studies undertaken to implementation of European Union wine reform. Dealu Mare is a vineyard where wine tourism could potentially increase the flow of tourists as well as improve their quality