Search results for: team based activity
32167 Anti-Anxiety Activity of Ethyl Acetate Extract of Flowers Nerium indicum
Authors: Deepak Suresh Mohale, Anil V. Chandewar
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Anxiety is defined as an exaggerated feeling of apprehension, uncertainty and fear. Nerium indicum is a well-known ornamental and medicinal plant belonging to the family Apocynaceae. A wide spectrum of biological activities has been reported with various constituents isolated from different parts of the plant. This study was conducted to investigate antianxiety activity of flower extract. Flowers were collected and dried in shade and coarsely powdered. Powdered mixture was extracted with ethyl acetate by maceration process. Extract of flowers obtained was subsequently dried in oven at 40-50 °C. This extract is then tested for antianxiety activity at low and high dose using elevated plus maze and light & dark model. Rats shown increased open arm entries and time spent in open arm in elevated Plus maze with treatment low and high dose of extract of Nerium indicum flower as compared to their respective control groups. In Light & dark Model, light box entries and time spent in light box increased with treatment low and high dose of extract of Nerium indicum flower as compared to their respective control groups. From result it is concluded that ethyl acetate extract of flower of Nerium indicum possess antianxiety activity at low and high dose.Keywords: antianxiety, anxiety, kaner, nerium indicum, social isolation
Procedia PDF Downloads 39232166 Insects and Meteorological Inventories in a Mango-Based Agroforestry System in Bangladesh
Authors: Md. Ruhul Amin, Shakura Namni, Md. Ramiz Uddin Miah, Md. Giashuddin Miah, Mohammad Zakaria, Sang Jae Suh, Yong Jung Kwon
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Insect species abundance and diversity associated with meteorological factors during January to June 2013 at a mango-based agroforestry research field in Bangladesh, and the effects of pests and pollinator species on mango are presented in this study. Among the collected and identified insects, nine species belong to 3 orders were found as pollinator, 11 species in 5 orders as pest, and 13 species in 6 orders as predator. The mango hopper, fruit fly and stone weevil appeared as major pest because of their high levels of abundance and infestation. The hoppers caused 100% inflorescence damage followed by fruit fly (51.7% fruit) and stone weevil (31.0% mature fruit). The major pests exerted significantly higher abundance compared to pollinator, predator and minor pests. Hemipteroid insects were most abundant (60%) followed by Diptera (21%), Hymenoptera (10%), Lepidoptera (5%), and Coleoptera (4%). Insect population increased with increasing trend of temperature and humidity, and revealed peak abundance during April-May. The flower visiting insects differed in their landing duration and showed preference to forage with time of a day. Their foraging activity was found to be peaked between 11.00 am to 01.00 pm. The activity of the pollinators led to higher level of fruit set. This study provides baseline information about the phenological patterns of insect abundance in an agroforestry research field which could be an indication to incorporate some aspects of pest management.Keywords: agroforestry, abundance, abiotic factors, insects, mango
Procedia PDF Downloads 44232165 Study of the Effect of Extraction Solvent on the Content of Total Phenolic, Total Flavonoids and the Antioxidant Activity of an Endemic Medicinal Plant Growing in Morocco
Authors: Aghoutane Basma, Naama Amal, Talbi Hayat, El Manfalouti Hanae, Kartah Badreddine
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Aromatic and medicinal plants are used by man for different needs, including food and medicinal needs for their biological properties attributed mainly to phenolic compounds and for their antioxidant capacity. In our study, the aim is to compare three extraction solvents by evaluating the contents of phenolic compounds, the contents of flavonoids, and the antioxidant activities of extracts from different methods of extracting the aerial part of an endemic medicinal plant from Morocco. This activity was also confirmed by three methods (2,2-diphenyl-1-picrylhydrazyl (DPPH), antioxidant reducing power of iron (FRAP), and total antioxidant capacity (CAT)). The results showed that this plant is rich in polyphenols and flavonoids, as well as it has a very important antioxidant capacity in whatever the solvent or the extraction method. This suggests the importance of using extracts from this plant as a new natural source of food additives and potent antioxidants in the food industry.Keywords: endemic plant of Morocco, phenolic compound, solvent, extraction technique, antioxidant activity
Procedia PDF Downloads 29832164 Developing Logistics Indices for Turkey as an an Indicator of Economic Activity
Authors: Gizem İntepe, Eti Mizrahi
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Investment and financing decisions are influenced by various economic features. Detailed analysis should be conducted in order to make decisions not only by companies but also by governments. Such analysis can be conducted either at the company level or on a sectoral basis to reduce risks and to maximize profits. Sectoral disaggregation caused by seasonality effects, subventions, data advantages or disadvantages may appear in sectors behaving parallel to BIST (Borsa Istanbul stock exchange) Index. Proposed logistic indices could serve market needs as a decision parameter in sectoral basis and also helps forecasting activities in import export volume changes. Also it is an indicator of logistic activity, which is also a sign of economic mobility at the national level. Publicly available data from “Ministry of Transport, Maritime Affairs and Communications” and “Turkish Statistical Institute” is utilized to obtain five logistics indices namely as; exLogistic, imLogistic, fLogistic, dLogistic and cLogistic index. Then, efficiency and reliability of these indices are tested.Keywords: economic activity, export trade data, import trade data, logistics indices
Procedia PDF Downloads 33732163 mHealth-based Diabetes Prevention Program among Mothers with Abdominal Obesity: A Randomized Controlled Trial
Authors: Jia Guo, Qinyuan Huang, Qinyi Zhong, Yanjing Zeng, Yimeng Li, James Wiley, Kin Cheung, Jyu-Lin Chen
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Context: Mothers with abdominal obesity, particularly in China, face challenges in managing their health due to family responsibilities. Existing diabetes prevention programs do not cater specifically to this demographic. Research Aim: To assess the feasibility, acceptability, and efficacy of an mHealth-based diabetes prevention program tailored for Chinese mothers with abdominal obesity in reducing weight-related variables and diabetes risk. Methodology: A randomized controlled trial was conducted in Changsha, China, where the mHealth group received personalized modules and health messages, while the control group received general health education. Data were collected at baseline, 3 months, and 6 months. Findings: The mHealth intervention significantly improved waist circumference, modifiable diabetes risk scores, daily steps, self-efficacy for physical activity, social support for physical activity, and physical health satisfaction compared to the control group. However, no differences were found in BMI and certain other variables. Theoretical Importance: The study demonstrates the feasibility and efficacy of a tailored mHealth intervention for Chinese mothers with abdominal obesity, emphasizing the potential for such programs to improve health outcomes in this population. Data Collection: Data on various variables including weight-related measures, diabetes risk scores, behavioral and psychological factors were collected at baseline, 3 months, and 6 months from participants in the mHealth and control groups. Analysis Procedures: Generalized estimating equations were used to analyze the data collected from the mHealth and control groups at different time points during the study period. Question Addressed: The study addressed the effectiveness of an mHealth-based diabetes prevention program tailored for Chinese mothers with abdominal obesity in improving various health outcomes compared to traditional general health education approaches. Conclusion: The tailored mHealth intervention proved to be feasible and effective in improving weight-related variables, physical activity, and physical health satisfaction among Chinese mothers with abdominal obesity, highlighting its potential for delivering diabetes prevention programs to this population.Keywords: type 2 diabetes, mHealth, obesity, prevention, mothers
Procedia PDF Downloads 5732162 Preparation and Characterization of Mixed Cu-Ag-Pd Oxide Supported Catalysts for Complete Catalytic Oxidation of Methane
Authors: Ts. Lazarova, V. Tumbalev, S. Atanacova-Vladimirova, G. Ivanov, A. Naydenov, D. Kovacheva
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Methane is a major Greenhouse Gas (GHG) that accounts for 14% of the world’s total amount of GHG emissions, originating mainly from agriculture, Coal mines, land fields, wastewater and oil and gas facilities. Nowadays the problem caused by the methane emissions has been a subject of an increased concern. One of the methods for neutralization of the methane emissions is it's complete catalytic oxidation. The efforts of the researchers are focused on the development of new types of catalysts and optimizing the existing catalytic systems in order to prevent the sintering of the palladium, providing at the same time a sufficient activity at temperatures below 500oC. The aim of the present work is to prepare mixed Cu-Ag-Pd oxide catalysts supported on alumina and to test them for methane complete catalytic oxidation. Cu-Ag-Pd/Al2O3 were prepared on a γ-Al2O3 (BET surface area = 220 m2/g) by the incipient wetness method using the corresponding metal nitrates (Cu:Ag = 90:10, Cu:Pd =97:3, Cu:Ag:Pd= 87:10:3) as precursors. A second set of samples were prepared with addition of urea to the metal nitrate solutions with the above mentioned ratios assuming increased dispersivity of the catalysts. The catalyst samples were dried at 100°C for 3 hours and calcined at 550°C for 30 minutes. Catalysts samples were characterized using X-ray diffraction (XRD), low temperature adsorption of nitrogen (BET) and scanning electron microscopy (SEM). The catalytic activity tests were carried out in a continuous flow type of reactor at atmospheric pressure. The effect of catalyst aging at 500 oC for 120 h on the methane combustion activity was also investigated. The results clearly indicate the synergetic effect of Ag and Pd on the catalytic activity.Keywords: catalysts, XRD, BET, SEM, catalytic oxidation
Procedia PDF Downloads 38232161 Education for Sustainability Using PBL on an Engineering Course at the National University of Colombia
Authors: Hernán G. Cortés-Mora, José I. Péna-Reyes, Alfonso Herrera-Jiménez
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This article describes the implementation experience of Project-Based Learning (PBL) in an engineering course of the Universidad Nacional de Colombia, with the aim of strengthening student skills necessary for the exercise of their profession under a sustainability framework. Firstly, we present a literature review on the education for sustainability field, emphasizing the skills and knowledge areas required for its development, as well as the commitment of the Faculty of Engineering of the Universidad Nacional de Colombia, and other engineering faculties of the country, regarding education for sustainability. This article covers the general aspects of the course, describes how students team were formed, and how their experience was during the first semester of 2017. During this period two groups of students decided to develop their course project aiming to solve a problem regarding a Non-Governmental Organization (NGO) that works with head-of-household mothers in a low-income neighborhood in Bogota (Colombia). Subsequently, we show how sustainability is involved in the course, how tools are provided to students, and how activities are developed as to strengthen their abilities, which allows them to incorporate sustainability in their projects while also working on the methodology used to develop said projects. Finally, we introduce the results obtained by the students who sent the prototypes of their projects to the community they were working on and the conclusions reached by them regarding the course experience.Keywords: sustainability, project-based learning, engineering education, higher education for sustainability
Procedia PDF Downloads 35232160 In vitro and in vivo Antiangiogenic Activity of Girinimbine Isolated from Murraya koenigii
Authors: Venoos Iman, Suzita Mohd Noor, Syam Mohan, Mohamad Ibrahim Noordin
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Girinimbine, a carbazole alkaloid was isolated from the stem bark and root of Murraya koenigii and its structure and purity was identified by HPLC and LC-MS. Here we report that Girinimbine strongly inhibit angiogenesis activity both in vitro and in vivo. MTT result showed that girinimbine inhibits cell proliferation of the HUVECS cell line in vitro. Result of endothelial cell invasion, migration, tube formation and wound healing assays also demonstrated significant time and does dependent inhibition by girinimbine. Moreover, girinibine mediates its anti-angiogenic activity through up- and down-regulation of angiogenic and anti-aniogenic proteins. Furthermore, anti-angiogenic potential of girinimbine was evidenced in vivo on zebrafish model. Girinimbine inhibited neo-vessels formation in zebrafish embryos during 24 hours exposure time. Together, these results demonstrated for the first time that girinimbine could effectively suppress angiogenesis and strongly suggest that it might be a novel angiogenesis inhibitor.Keywords: anti-angiogenic, carbazole alkaloid, girinimbine, zebrafish
Procedia PDF Downloads 37632159 Developing Social Responsibility Values in Nascent Entrepreneurs through Role-Play: An Explorative Study of University Students in the United Kingdom
Authors: David W. Taylor, Fernando Lourenço, Carolyn Branston, Paul Tucker
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There are an increasing number of students at Universities in the United Kingdom engaging in entrepreneurship role-play to explore business start-up as a career alternative to employment. These role-play activities have been shown to have a positive influence on students’ entrepreneurial intentions. Universities also play a role in developing graduates’ awareness of social responsibility. However, social responsibility is often missing from these entrepreneurship role-plays. It is important that these role-play activities include the development of values that support social responsibility, in-line with those running hybrid, humane and sustainable enterprises, and not simply focus on profit. The Young Enterprise (YE) Start-Up programme is an example of a role-play activity that is gaining in popularity amongst United Kingdom Universities seeking ways to give students insight into a business start-up. A Post-92 University in the North-West of England has adapted the traditional YE Directorship roles (e.g., Marketing Director, Sales Director) by including a Corporate Social Responsibility (CSR) Director in all of the team-based YE Start-Up businesses. The aim for introducing this Directorship was to observe if such a role would help create a more socially responsible value-system within each company and in turn shape business decisions. This paper investigates role-play as a tool to help enterprise educators develop socially responsible attitudes and values in nascent entrepreneurs. A mixed qualitative methodology approach has been used, which includes interviews, role-play, and reflection, to help students develop positive value characteristics through the exploration of unethical and selfish behaviors. The initial findings indicate that role-play helped CSR Directors learn and gain insights into the importance of corporate social responsibility, influenced the values and actions of their YE Start-Ups, and increased the likelihood that if the participants were to launch a business post-graduation, that the intent would be for the business to be socially responsible. These findings help inform educators on how to develop socially responsible nascent entrepreneurs within a traditionally profit orientated business model.Keywords: student entrepreneurship, young enterprise, social responsibility, role-play, values
Procedia PDF Downloads 15132158 Immunoregulatory Cytokines and Chemokines Synthesis in Endurance Exercises
Authors: Roman Khanferyan
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Endurance exercises and strenuous muscle activity are accompanied by multiple immune dysfunctions due to the activation of cytokines and chemokines synthesis. This study assesses changes in the synthesis of immune regulatory mediators in elite athletes during endurance sports activity. The concentrations of cytokines/chemokines (IL-2, IL-6, IL-8, IL-10, IL-18, MIP-1 beta, GRO-alpha, RANTES, SDF-1a, VEGF) in sera of hockey athletes (n=33) and in supernatants of 24-h cultivated peripheral blood mononuclear cells (PBMC) of boxers (n=6) assayed by ELISA and Luminex xMAP multiplex assays. Estimation of body composition studied by using bioimpedance technology. The dietary energy consumption per person has been estimated using an album of different sizes of portions of the most frequently consumed foods. It has been demonstrated that endurance sports activity enhances the secretions of most pro- and anti-inflammatory cytokines and chemokines in more than 2-6 fold. The study demonstrated that the high increase of more than 3-4 times in the concentration of IL-18 in sera of athletes (327.86 + 45.67 pg/ml) didn’t correlate with BMI (p=0.040) but demonstrated a low correlation with MMI (p=0.234) and BMR (p=0,231). The opposite impact on the concentration of IL-10 has been demonstrated in athletes. It has been shown a negative correlation between its concentration and BMI (p= - 0.251), MMI (p= - 0.327), and BMR (p= - 0.301). In vitro studies in boxers showed greater amounts of chemokines in the PBMC supernatants, including MIP-1β, GRO-α, RANTES, SDF-1α, and IL-8 (P<0.05). At the same time, healthy controls had greater supernatant levels of MCP-1, Eotaxin, and MIP-1α. The study demonstrated a high correlation between physical activity, usual athletes' diet, and consumption of specialized sports nutrition products.Keywords: sport nutrition, cytokines, chemokines, endurace exercises
Procedia PDF Downloads 4332157 Comparative Study on the Effect of Substitution of Li and Mg Instead of Ca on Structural and Biological Behaviors of Silicate Bioactive Glass
Authors: Alireza Arab, Morteza Elsa, Amirhossein Moghanian
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In this study, experiments were carried out to achieve a promising multifunctional and modified silicate based bioactive glass (BG). The main aim of the study was investigating the effect of lithium (Li) and magnesium (Mg) substitution, on in vitro bioactivity of substituted-58S BG. Moreover, it is noteworthy to state that modified BGs were synthesized in 60SiO2–(36-x)CaO–4P2O5–(x)Li2O and 60SiO2–(36-x)CaO–4P2O5–(x)MgO (where x = 0, 5, 10 mol.%) quaternary systems, by sol-gel method. Their performance was investigated through different aspects such as biocompatibility, antibacterial activity as well as their effect on alkaline phosphatase (ALP) activity, and proliferation of MC3T3 cells. The antibacterial efficiency was evaluated against methicillin-resistant Staphylococcus aureus bacteria. To do so, CaO was substituted with Li2O and MgO up to 10 mol % in 58S-BGs and then samples were immersed in simulated body fluid up to 14 days and then, characterized by X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma atomic emission spectrometry, and scanning electron microscopy. Results indicated that this modification led to a retarding effect on in vitro hydroxyapatite (HA) formation due to the lower supersaturation degree for nucleation of HA compared with 58s-BG. Meanwhile, magnesium revealed further pronounced effect. The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and ALP analysis illustrated that substitutions of both Li2O and MgO, up to 5 mol %, had increasing effect on biocompatibility and stimulating proliferation of the pre-osteoblast MC3T3 cells in comparison to the control specimen. Regarding to bactericidal efficiency, the substitution of either Li or Mg for Ca in the 58s BG composition led to statistically significant difference in antibacterial behaviors of substituted-BGs. Meanwhile, the sample containing 5 mol % CaO/Li2O substitution (BG-5L) was selected as a multifunctional biomaterial in bone repair/regeneration due to the improved biocompatibility, enhanced ALP activity and antibacterial efficiency among all of the synthesized L-BGs and M-BGs.Keywords: alkaline, alkaline earth, bioactivity, biomedical applications, sol-gel processes
Procedia PDF Downloads 10832156 Physical Activity Patterns and Status of Adolescent Learners from Low and Middle Socio-Economic Status Communities in Kwazulu-Natal Province
Authors: Patrick Mkhanyiseli Zimu
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A sedentary lifestyle and insufficient physical activity (PA) increases the risk of developing chronic non-communicable diseases (NCDs). Knowing the PA levels and patterns of adolescents from different socio-economic backgrounds is important to direct programs at schools and in communities to prevent NCDs risk factors, which can have long-term effects on the health of the adolescents. The study aimed to investigate adolescent PA levels, patterns, and influencing factors (age, gender, socio-economic status). The 353 participants (203 females and 150 males) from eight low socio-economic (LSES) and middle socio-economic (MSES) public secondary schools completed a Physical Activity Questionnaire for Adolescents (PAQ-A). The PAQ-A is a seven day recall instrument that assesses general estimates of PA levels and patterns for high school learners in Grades 9-12 and provides a summary of physical activity scores derived from seven items, each scored on a 5-point Likert scale. The seven items were PA during spare time and five domains (during physical education, lunch break, after school, in the evenings, on the weekend) and selecting one statement that described participant’s physical activity behaviour. The PA Levels (x̄=2.61, SD=.74) were below the international PA cut-off points of x̄=2.75. Physical education (PE) showed the highest PA score (x̄=3.05, SD=1.21) and lunch break showed the lowest PA score (x̄=2.09, SD=1.14). Positive correlations occurred between PA levels and SES (r=.122, p=0.022), and PA and gender (r=.223, p= 0.0001). LSES participant’s PA score was significantly lower (x̄=2.52; SD=.73) than those from MSES (x̄=2.70; SD=.74, p=0.022). Adolescents from low and middle socio-economic status communities are not sufficiently active. Their average PA score of 2.61 is below the PAQ-A global criterion referenced cut-off points of 2.75, which is considered sufficiently physically active for adolescents to ensure both short- and long-term health benefits. As adolescents are not sufficiently active, collaborative school and community PA programs need to be implemented to supplement physical education in order to prevent short- and long-term health problems.Keywords: adolescents, health promotion, physical activity, physical education
Procedia PDF Downloads 9532155 Chemical Composition and Antibacterial Activity of the Essential Oils from Bunium alpinum and Bunium incrassatum
Authors: Hayet El Kolli, Hocine Laouer
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Bunium in the world comprises about 50 to 100 species, mostly distributed in: Algeria, Italy, Pakistan, Iran, and South Africa. Bunium species have several uses like: Bunium persicum which is commonly used as antispasmodic, carminative, anti-obesity and lactogage. This plant have been widely used as an additive in food stuff such as in bread cooking, rice and yoghurt for its carminative, anti-dyspepsia and antispasmodic effect. The B. paucifolium oil has a wide spectrum of action against moulds, yeast and bacteria. The chemical compositions of Bunium incrassatum and Bunium alpinum essential oils were carry out by GC and GC/MS. Therefore, antibacterial activity of two oils was investigated by disk diffusion method against Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Salmonella typhimurium ATCC 1331, Staphylococcus aureus ATCC 25923, Klebsiella pneumoniae ATCC 700603, Bacillus cereus ATCC 10876, Enterococcus faecalis ATCC 49452, Lysteria monocytogenes ATCC 15313, Citrobacter freundii ATCC 8090, Proteus mirabilis ATCC 35659. A moderate antibacterial activity was found. In conclusion, it is found that essential oils of the two species are rich in sesquiterpens and other oxygenated compounds. These compounds have been reported to show bactericidal activity and the presence of phenolic compounds makes them useful antioxidants so that results confirm some ethnopharmacologique applications of these two oils of Bunium.Keywords: Bunium alpinum, Bunium incrassatum, apiaceae, essential oil, sesquiterpens, phenols, antibacterial, antioxidant activities
Procedia PDF Downloads 37132154 Antibacterial and Antifungal Activity of Essential Oil of Eucalyptus camendulensis on a Few Bacteria and Fungi
Authors: M. Mehani, N. Salhi, T. Valeria, S. Ladjel
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Red River Gum (Eucalyptus camaldulensis) is a tree of the genus Eucalyptus widely distributed in Algeria and in the world. The value of its aromatic secondary metabolites offers new perspectives in the pharmaceutical industry. This strategy can contribute to the sustainable development of our country. Preliminary tests performed on the essential oil of Eucalyptus camendulensis showed that this oil has antibacterial activity vis-à-vis the bacterial strains (Enterococcus feacalis, Enterobacter cloaceai, Proteus microsilis, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa) and antifungic (Fusarium sporotrichioide and Fusarium graminearum). The culture medium used was nutrient broth Muller Hinton. The interaction between the bacteria and the essential oil is expressed by a zone of inhibition with diameters of MIC indirectly expression of. And we used the PDA medium to determine the fungal activity. The extraction of the aromatic fraction (essentially oil- hydrolat) of the fresh aerian part of the Eucalyptus camendulensis was performed by hydrodistillation. The average essential oil yield is 0.99%. The antimicrobial and fungal study of the essential oil and hydrosol showed a high inhibitory effect on the growth of pathogens.Keywords: essential oil, Eucalyptus camendulensis, bacteria and fungi, red river gum
Procedia PDF Downloads 23532153 Anti Staphylococcus aureus and Methicillin Resistant Staphylococcus aureus Action of Thermophilic Fungi Acrophialophora levis IBSD19 and Determination of Its Mode of Action Using Electron Microscopy
Authors: Shivankar Agrawal, Indira Sarangthem
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Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the major causes of healthcare-associated and community-onset infections worldwide. Hence the search for non-toxic natural compounds having antibacterial activity has intensified for future drug development. The exploration of less studied niches of Earth can highly increase the possibility to discover novel bioactive compounds. Therefore, in this study, the cultivable fraction of fungi from the sediments of natural hot springs has been studied to mine potential fungal candidates with antibacterial activity against the human pathogen Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus. We isolated diverse strains of thermophilic fungi from a collection of samples from sediment. Following a standard method, we isolated a promising thermophilic fungus strain IBSD19, identified as Acrophialophora levis, possessing the potential to produce an anti-Staphylococcus aureus agent. The growth conditions were optimized and scaled to fermentation, and its produced extract was subjected to chemical extraction. The ethyl acetate fraction was found to display significant activity against Staphylococcus aureus and MRSA with a minimum inhibitory concentration (MIC) of 0.5 mg/ml and 4 mg/ml, respectively. The cell membrane integrity assay and SEM suggested that the fungal metabolites cause bacteria clustering and further lysis of the cell.Keywords: antibacterial activity, antioxidant, fungi, Staphylococcus aureus, MRSA, thermophiles
Procedia PDF Downloads 13432152 Molecular Insights into the 5α-Reductase Inhibitors: Quantitative Structure Activity Relationship, Pre-Absorption, Distribution, Metabolism, and Excretion and Docking Studies
Authors: Richa Dhingra, Monika, Manav Malhotra, Tilak Raj Bhardwaj, Neelima Dhingra
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5-Alpha-reductases (5AR), a membrane bound, NADPH dependent enzyme and convert male hormone testosterone (T) into more potent androgen dihydrotestosterone (DHT). DHT is the required for the development and function of male sex organs, but its overproduction has been found to be associated with physiological conditions like Benign Prostatic Hyperplasia (BPH). Thus the inhibition of 5ARs could be a key target for the treatment of BPH. In present study, 2D and 3D Quantitative Structure Activity Relationship (QSAR) pharmacophore models have been generated for 5AR based on known inhibitory concentration (IC₅₀) values with extensive validations. The four featured 2D pharmacophore based PLS model correlated the topological interactions (–OH group connected with one single bond) (SsOHE-index); semi-empirical (Quadrupole2) and physicochemical descriptors (Mol. wt, Bromines Count, Chlorines Count) with 5AR inhibitory activity, and has the highest correlation coefficient (r² = 0.98, q² =0.84; F = 57.87, pred r² = 0.88). Internal and external validation was carried out using test and proposed set of compounds. The contribution plot of electrostatic field effects and steric interactions generated by 3D-QSAR showed interesting results in terms of internal and external predictability. The well validated 2D Partial Least Squares (PLS) and 3D k-nearest neighbour (kNN) models were used to search novel 5AR inhibitors with different chemical scaffold. To gain more insights into the molecular mechanism of action of these steroidal derivatives, molecular docking and in silico absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Studies have revealed the hydrophobic and hydrogen bonding of the ligand with residues Alanine (ALA) 63A, Threonine (THR) 60A, and Arginine (ARG) 456A of 4AT0 protein at the hinge region. The results of QSAR, molecular docking, in silico ADME studies provide guideline and mechanistic scope for the identification of more potent 5-Alpha-reductase inhibitors (5ARI).Keywords: 5α-reductase inhibitor, benign prostatic hyperplasia, ligands, molecular docking, QSAR
Procedia PDF Downloads 16332151 Mn3O4-NiFe Layered Double Hydroxides(LDH)/Carbon Composite Cathode for Rechargeable Zinc-Air Battery
Authors: L. K. Nivedha, V. Maruthapandian, R. Kothandaraman
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Rechargeable zinc-air batteries (ZAB) are gaining significant research attention owing to their high energy density and copious zinc resources worldwide. However, the unsolved obstacles such as dendrites, passivation, depth of discharge and the lack of an efficient cathode catalyst restrict their practical application1. By and large, non-noble transition metal-based catalysts are well-reputed materials for catalysing oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) with greater stability in alkaline medium2. Herein, we report the synthesis and application of Mn₃O4-NiFeLDH/Carbon composite as a cathode catalyst for rechargeable ZAB. The synergetic effects of the mixed transition metals (Mn/Ni/Fe) have aided in catalysing ORR and OER in alkaline electrolyte with a shallow potential gap of 0.7 V. The composite, by its distinctive physicochemical characteristics, shows an excellent OER activity with a current density of 1.5 mA cm⁻² at a potential of 1.6 V and a superior ORR activity with an onset potential of 0.8 V when compared with their counterparts. Nevertheless, the catalyst prefers a two-electron pathway for the electrochemical reduction of oxygen which results in a limiting current density of 2.5 mA cm⁻². The bifunctional activity of the Mn₃O₄-NiFeLDH/Carbon composite was utilized in developing rechargeable ZAB. The fully fabricated ZAB delivers an open circuit voltage of 1.4 V, a peak power density of 70 mW cm⁻², and a specific capacity of 800 mAh g⁻¹ at a current density of 20 mA cm⁻² with an average discharge voltage of 1 V and the cell is operable upto 50 mA cm-2. Rechargeable ZAB demonstrated over 110 h at 10 mA cm⁻². Further, the cause for the diminished charge-discharge performance experienced beyond the 100th cycle was investigated, and carbon corrosion was testified using Infrared spectroscopy.Keywords: rechargeable zinc-air battery, oxygen evolution reaction, bifunctional catalyst, alkaline medium
Procedia PDF Downloads 8032150 Optimising Transcranial Alternating Current Stimulation
Authors: Robert Lenzie
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Transcranial electrical stimulation (tES) is significant in the research literature. However, the effects of tES on brain activity are still poorly understood at the surface level, the Brodmann Area level, and the impact on neural networks. Using a method like electroencephalography (EEG) in conjunction with tES might make it possible to comprehend the brain response and mechanisms behind published observed alterations in more depth. Using a method to directly see the effect of tES on EEG may offer high temporal resolution data on the brain activity changes/modulations brought on by tES that correlate to various processing stages within the brain. This paper provides unpublished information on a cutting-edge methodology that may reveal details about the dynamics of how the human brain works beyond what is now achievable with existing methods.Keywords: tACS, frequency, EEG, optimal
Procedia PDF Downloads 8332149 Biodegradable Drinking Straws Made From Naturally Dried and Fallen Coconut Leaves: Impact on Rural Circular Economy and Environmental Sustainability
Authors: Saji Varghese
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Naturally dried and fallen coconut leaves and found in abundance in India and other coconut growing regions of the world. These fallen coconut leaves are usually burnt by farmers in landfills and open kitchens, leading to CO2 and particulate emissions. The innovation of biodegradable drinking straws from naturally dried and fallen coconut leaves by this researcher and his team has opened up opportunities to create value out of this agri-waste leading to i. prevention of burning of these discarded leaves ii. income generating opportunities to women in rural areas of coconut growing regions iii. an alternative to single use plastic straws. The team has developed five special purpose machines, which are deployed in the three villages on a pilot basis where 36 women are employed. The women are trained in the use of these machines, and the straws which are in good demand are sold globally. The present paper analyses the prospective impact of this innovation on the incomes of women working at the straw production centres and the consequent impact on their standards of living, The paper also analyses the impact of this innovation in the reduction of CO2 and particulate emissions and makes a case for support from Govt and Non Govt organizations in coconut growing regions to set up straw production centres to boost rural circular economy and to reduce carbon footprint and eliminate plastic pollutionKeywords: drinking straws, coconut leaves, circular economy, sustainability
Procedia PDF Downloads 13832148 Improving School Design through Diverse Stakeholder Participation in the Programming Phase
Authors: Doris C. C. K. Kowaltowski, Marcella S. Deliberador
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The architectural design process, in general, is becoming more complex, as new technical, social, environmental, and economical requirements are imposed. For school buildings, this scenario is also valid. The quality of a school building depends on known design criteria and professional knowledge, as well as feedback from building performance assessments. To attain high-performance school buildings, a design process should add a multidisciplinary team, through an integrated process, to ensure that the various specialists contribute at an early stage to design solutions. The participation of stakeholders is of special importance at the programming phase when the search for the most appropriate design solutions is underway. The composition of a multidisciplinary team should comprise specialists in education, design professionals, and consultants in various fields such as environmental comfort and psychology, sustainability, safety and security, as well as administrators, public officials and neighbourhood representatives. Users, or potential users (teachers, parents, students, school officials, and staff), should be involved. User expectations must be guided, however, toward a proper understanding of a response of design to needs to avoid disappointment. In this context, appropriate tools should be introduced to organize such diverse participants and ensure a rich and focused response to needs and a productive outcome of programming sessions. In this paper, different stakeholder in a school design process are discussed in relation to their specific contributions and a tool in the form of a card game is described to structure the design debates and ensure a comprehensive decision-making process. The game is based on design patterns for school architecture as found in the literature and is adapted to a specific reality: State-run public schools in São Paulo, Brazil. In this State, school buildings are managed by a foundation called Fundação para o Desenvolvimento da Educação (FDE). FDE supervises new designs and is responsible for the maintenance of ~ 5000 schools. The design process of this context was characterised with a recommendation to improve the programming phase. Card games can create a common environment, to which all participants can relate and, therefore, can contribute to briefing debates on an equal footing. The cards of the game described here represent essential school design themes as found in the literature. The tool was tested with stakeholder groups and with architecture students. In both situations, the game proved to be an efficient tool to stimulate school design discussions and to aid in the elaboration of a rich, focused and thoughtful architectural program for a given demand. The game organizes the debates and all participants are shown to spontaneously contribute each in his own field of expertise to the decision-making process. Although the game was specifically based on a local school design process it shows potential for other contexts because the content is based on known facts, needs and concepts of school design, which are global. A structured briefing phase with diverse stakeholder participation can enrich the design process and consequently improve the quality of school buildings.Keywords: architectural program, design process, school building design, stakeholder
Procedia PDF Downloads 40532147 Synthesis and Theoretical Calculations of Carbazole Substituted Pyridopyrimidine Urea/Thioure Derivatives and Studies Their PPO Enzyme Activity
Authors: Arleta Rifati Nixha, Mustafa Arslan, Adem Ergün, Nahit Gencer
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Polyphenol oxidase (PPO), sometimes referred to as phenol oxidase, catecholase, phenolase, catechol oxidase, or even tyrosinase, is considered to be an o-dipenol. PPO (EC 1.14.18.1), a multifunctional copper containing enzyme, is widely distributed in nature. It catalyzes two distinct reactions of melanin synthesis: a hydroxylation of monophenols to o-diphenols (monophenolase activity) and an oxidation of o-diphenols to o-quinones (diphenolase activity), both using molecular oxygen. Additionaly, investigation demonstrated that various dermatological disorders, such as age spots and freckle, were caused by the accumulation of an excessive level of epidermal pigmentation. Tyrosinase has also been linked to Parkinson’s and other neurodegenerative diseases. Nitrogen heterocycles have received a great deal of attention in the literature because of biological properties. Especially, among these heterocyclic systems, pyridine containing compounds have been the subject of expanding research efforts in heteroaromatic and biological chemistry. The pyrido [2,3-d] pyrimidine heterocycles, which are those annelated to a pyrimidine ring, are important because of their wide range of biological and pharmaceutical applications (i.e., bronchodilators, vasodilators) and their anti-allergic, cardiotonic, antihypertensive, and hepatoprotective activities. In this study series of 12 new carbazole substituted pyridopyrimidine urea(thiourea) derivatives were synthesized and evaluated effect on PPO. Additionally, we presented structure-activity relationship analyses and theoretical calculations of the compounds.Keywords: carbazole, pyridopyrimidine, urea, thiourea, tyrosinase inhibitors
Procedia PDF Downloads 43932146 Dynamic Process Model for Designing Smart Spaces Based on Context-Awareness and Computational Methods Principles
Authors: Heba M. Jahin, Ali F. Bakr, Zeyad T. Elsayad
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As smart spaces can be defined as any working environment which integrates embedded computers, information appliances and multi-modal sensors to remain focused on the interaction between the users, their activity, and their behavior in the space; hence, smart space must be aware of their contexts and automatically adapt to their changing context-awareness, by interacting with their physical environment through natural and multimodal interfaces. Also, by serving the information used proactively. This paper suggests a dynamic framework through the architectural design process of the space based on the principles of computational methods and context-awareness principles to help in creating a field of changes and modifications. It generates possibilities, concerns about the physical, structural and user contexts. This framework is concerned with five main processes: gathering and analyzing data to generate smart design scenarios, parameters, and attributes; which will be transformed by coding into four types of models. Furthmore, connecting those models together in the interaction model which will represent the context-awareness system. Then, transforming that model into a virtual and ambient environment which represents the physical and real environments, to act as a linkage phase between the users and their activities taking place in that smart space . Finally, the feedback phase from users of that environment to be sure that the design of that smart space fulfill their needs. Therefore, the generated design process will help in designing smarts spaces that can be adapted and controlled to answer the users’ defined goals, needs, and activity.Keywords: computational methods, context-awareness, design process, smart spaces
Procedia PDF Downloads 33132145 Assessing the Impact of Physical Inactivity on Dialysis Adequacy and Functional Health in Peritoneal Dialysis Patients
Authors: Mohammad Ali Tabibi, Farzad Nazemi, Nasrin Salimian
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Background: Peritoneal dialysis (PD) is a prevalent renal replacement therapy for patients with end-stage renal disease. Despite its benefits, PD patients often experience reduced physical activity and physical function, which can negatively impact dialysis adequacy and overall health outcomes. Despite the known benefits of maintaining physical activity in chronic disease management, the specific interplay between physical inactivity, physical function, and dialysis adequacy in PD patients remains underexplored. Understanding this relationship is essential for developing targeted interventions to enhance patient care and outcomes in this vulnerable population. This study aims to assess the impact of physical inactivity on dialysis adequacy and functional health in PD patients. Methods: This cross-sectional study included 135 peritoneal dialysis patients from multiple dialysis centers. Physical inactivity was measured using the International Physical Activity Questionnaire (IPAQ), while physical function was assessed using the Short Physical Performance Battery (SPPB). Dialysis adequacy was evaluated using the Kt/V ratio. Additional variables such as demographic data, comorbidities, and laboratory parameters were collected to control for potential confounders. Statistical analyses were performed to determine the relationships between physical inactivity, physical function, and dialysis adequacy. Results: The study cohort comprised 70 males and 65 females with a mean age of 55.4 ± 13.2 years. A significant proportion of the patients (65%) were categorized as physically inactive based on IPAQ scores. Inactive patients demonstrated significantly lower SPPB scores (mean 6.2 ± 2.1) compared to their more active counterparts (mean 8.5 ± 1.8, p < 0.001). Dialysis adequacy, as measured by Kt/V, was found to be suboptimal (Kt/V < 1.7) in 48% of the patients. There was a significant positive correlation between physical function scores and Kt/V values (r = 0.45, p < 0.01), indicating that better physical function is associated with higher dialysis adequacy. Also, there was a significant negative correlation between physical inactivity and physical function (r = -0.55, p < 0.01). Additionally, physically inactive patients had lower Kt/V ratios compared to their active counterparts (1.3 ± 0.3 vs. 1.8 ± 0.4, p < 0.05). Multivariate regression analysis revealed that physical inactivity was an independent predictor of reduced dialysis adequacy (β = -0.32, p < 0.01) and poorer physical function (β = -0.41, p < 0.01) after adjusting for age, sex, comorbidities, and dialysis vintage. Conclusion: This study underscores the critical role of physical activity and physical function in maintaining adequate dialysis in peritoneal dialysis patients. These findings highlight the need for targeted interventions to promote physical activity in this population to improve their overall health outcomes. Future research should focus on developing and evaluating exercise programs tailored for PD patients to enhance their physical function and dialysis adequacy. The findings suggest that interventions aimed at increasing physical activity and improving physical function may enhance dialysis adequacy and overall health outcomes in this population. Further research is warranted to explore the mechanisms underlying these associations and to develop targeted strategies for enhancing patient care.Keywords: inactivity, physical function, peritoneal dialysis, dialysis adequacy
Procedia PDF Downloads 3532144 Identification of Ice Hockey World Championship International Sports Event through Brand Personality
Authors: Eva Čáslavová, Andrej Višněvský
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This research focused on the dimensions of brand personality of the Ice Hockey World Championship sporting event. The authors compared the elements in relation to different demographic groups including gender, age, level of education and student status of the population of Prague. Moreover, the differences of opinions of respondents who had experience of visiting a sports event and those who had not were assessed. In the research, the modified brand personality scale was used. This modified scale consists of five dimensions: responsibility, activity, toughness, individuality and emotionality, none of which was previously tested. The authors had an intentional sample of 291 respondents from Prague available, ranging in age from 18 years to 75 years, with either a high school or university education. The respondents rated the characteristic features in a seven-point Likert Scale and the data was collected in November 2012. The results suggest that the Ice Hockey World Championship is most identified with these dimensions: responsibility, emotionality and activity. Men had higher mean scores (4.93) on the Likert Scale in the emotionality dimension, while women had higher mean scores (4.91) in the activity dimension. Those respondents with experience visiting an Ice Hockey World Championship match had the highest mean score (5.10) in the emotionality dimension. This research had expected to show more pronounced mean values (above six) on the Likert scale in the emotionality and activity dimensions that more strongly characterize the brand personality of the Ice Hockey World Championship, however this expectation was not confirmed.Keywords: dimensions, brand personality, ice hockey, international sports event, marketing
Procedia PDF Downloads 23632143 Fatty Acid Composition, Total Sugar Content and Anti-Diabetic Activity of Methanol and Water Extracts of Nine Different Fruit Tree Leaves Collected from Mediterranean Region of Turkey
Authors: Sengul Uysal, Gokhan Zengin, Abdurrahman Aktumsek, Sukru Karatas
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In this research, we determined the total sugar content, fatty acid compositions and α-amylase and α-glucosidase inhibitory activity of methanolic and water extracts of nine different fruit tree leaves. α-amylase and α-glycosidase inhibitory activity were determined by using Caraway-Somogyi–iodine/potassium iodide (IKI) and 4-nitrophenyl-α-D-glucopyranoside (PNPG) as substrate, respectively. Total sugar content of the nine different fruit tree leaves varies from 281.02 mg GE/g (glucose equivalents) to 643.96 mg GE/g. Methanolic extract from avocado leaves had the strongest in α-amylase and α-glucosidase inhibitory activity, 69.21% and 96.26 %, respectively. Fatty acid composition of nine fruit tree leaves was characterized by GC (gas chromatography) and twenty-four components were identified. Among the tested fruit tree leaves, the main component was linolenic acid (49.09%). The level of essential fatty acids are over 50% in mulberry, grape and loquat leaves. PUFAs (polyunsaturated fatty acids) were major group of fatty acids present in oils of mulberry, fig, pomegranate, grape, and loquat leaves. Therefore, these oils can be considered as a good source of polyunsaturated fatty acids. Furthermore, avocado can be regarded as a new source for diabetic therapies.Keywords: fatty acid compositions, total sugar contents, α-amylase, α-glucosidase, fruit tree leaves, Turkey
Procedia PDF Downloads 48632142 Investigation of Information Security Incident Management Based on International Standard ISO/IEC 27002 in Educational Hospitals in 2014
Authors: Nahid Tavakoli, Asghar Ehteshami, Akbar Hassanzadeh, Fatemeh Amini
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Introduction: The Information security incident management guidelines was been developed to help hospitals to meet their information security event and incident management requirements. The purpose of this Study was to investigate on Information Security Incident Management in Isfahan’s educational hospitals in accordance to ISO/IEC 27002 standards. Methods: This was a cross-sectional study to investigate on Information Security Incident Management of educational hospitals in 2014. Based on ISO/IEC 27002 standards, two checklists were applied to check the compliance with standards on Reporting Information Security Events and Weakness and Management of Information Security Incidents and Improvements. One inspector was trained to carry out the assessments in the hospitals. The data was analyzed by SPSS. Findings: In general the score of compliance Information Security Incident Management requirements in two steps; Reporting Information Security Events and Weakness and Management of Information Security Incidents and Improvements was %60. There was the significant difference in various compliance levels among the hospitals (p-value32141 Preparation, Characterization, and Antimicrobial Activity of Carboxymethyl Chitosan Schiff Bases with Different Benzaldehyde Derivatives
Authors: Nadia A. Mohamed, Magdy W. Sabaa, Ahmed H. H. El-Ghandour, Marwa M. Abdel-Aziz, Omayma F. Abdel-Gawad
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Eighteen carboxymethyl chitosan (CMCh) schiff bases and their reduced derivatives have been synthesized. They were characterized by spectral analyses (FT-IR and H1-NMR) and scanning electron microscopy observation. Their antibacterial activities against Streptococcus pneumoniae (RCMB 010010), Bacillis subtilis (RCMB 010067), as Gram positive bacteria and Escherichia coli (RCMB 010052) as Gram negative bacteria and the antifungal activity against Aspergillus fumigatus (RCMB 02568), Geotricum candidum (RCMB 05097), and Candida albicans (RCMB 05031) were examined using agar disk diffusion method. The results demonstrate how the antibacterial and the antifungal activity are clearly affected by both the nature and position of the substituent groups in the aryl ring of the prepared derivatives. CMCh-4-nitroBenz Schiff base and its reduced form show higher antimicrobial activity comparing with other para substituted derivatives. CMCh-4-nitroBenz Schiff base: 18.3, 17, and 15.6 mm against Bacillis subtilis, Streptococcus pneumonia, and Escherichia coli respectively and 16.2, 17.3, and 16.4 mm against Aspergillus fumigates, Geotricum candidum, and Candida albicans respectively. CMCh-4-nitroBenz reduced form: 19.5, 18.7, and 16.2 mm against Bacillis subtilis, Streptococcus pneumonia, and Escherichia coli respectively and 17.5, 19.5, and 17.4 mm against Aspergillus fumigates, Geotricum candidum, and Candida albicans respectively. Also CMCh-3-bromoBenz show good results; CMCh-3-bromoBenz schiff base: 19.2, 16.9, and 14.6 mm Bacillis subtilis, Streptococcus pneumonia, and Escherichia coli respectively and 18.4, 17.6, and 15.9 mm against Aspergillus fumigates, Geotricum candidum, and Candida albicans respectively.Keywords: chitosan, schiff base, minimum inhibition concentration, antimicrobial activity
Procedia PDF Downloads 46132140 A Comparative Approach for Modeling the Toxicity of Metal Mixtures in Two Ecologically Related Three-Spined (Gasterosteus aculeatus L.) And Nine-Spined (Pungitius pungitius L.) Sticklebacks
Authors: Tomas Makaras
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Sticklebacks (Gasterosteiformes) are increasingly used in ecological and evolutionary research and become well-established role as model species for biologists. However, ecotoxicology studies concerning behavioural effects in sticklebacks regarding stress responses, mainly induced by chemical mixtures, have hardly been addressed. Moreover, although many authors in their studies emphasised the similarity between three-spined and nine-spined stickleback in morphological, neuroanatomical and behavioural adaptations to environmental changes, several comparative studies have revealed considerable differences between these species in and their susceptibility and resistance to variousstressors in laboratory experiments. The hypothesis of this study was that three-spined and nine-spined stickleback species will demonstrate apparent differences in response patterns and sensitivity to metal-based chemicals stimuli. For this purpose, we investigated the swimming behaviour (including mortality rate based on 96-h LC50 values) of two ecologically similar three-spined (Gasterosteusaculeatus) and nine-spined sticklebacks (Pungitiuspungitius) to short-term (up to 24 h) metal mixture (MIX) exposure. We evaluated the relevance and efficacy of behavioural responses of test species in the early toxicity assessment of chemical mixtures. Fish exposed to six (Zn, Pb, Cd, Cu, Ni and Cr) metals in the mixture were either singled out by the Water Framework Directive as priority or as relevant substances in surface water, which was prepared according to the environmental quality standards (EQSs) of these metals set for inland waters in the European Union (EU) (Directive 2013/39/EU). Based on acute toxicity results, G. aculeatus found to be slightly (1.4-fold) more tolerant of MIX impact than those of P. pungitius specimens. The performed behavioural analysis showed the main effect on the interaction between time, species and treatment variables. Although both species exposed to MIX revealed a decreasing tendency in swimming activity, these species’ responsiveness to MIX was somewhat different. Substantial changes in the activity of G. aculeatus were established after 3-h exposure to MIX solutions, which was 1.43-fold lower, while in the case of P. pungitius, 1.96-fold higher than established 96-h LC50 values for each species. This study demonstrated species-specific differences in response sensitivity to metal-based water pollution, indicating behavioural insensitivity of P. pungitiuscompared to G. aculeatus. While many studies highlight the usefulness and suitability of nine-spined sticklebacks for evolutionary and ecological research, attested by their increasing popularity in these fields, great caution must be exercised when using them as model species in ecotoxicological research to probe metal contamination. Meanwhile, G. aculeatus showed to be a promising bioindicator species in the environmental ecotoxicology field.Keywords: acute toxicity, comparative behaviour, metal mixture, swimming activity
Procedia PDF Downloads 16232139 Use of Zikani’s Ribosome Modulating Agents for Treating Recessive Dystrophic & Junctional Epidermolysis Bullosa with Nonsense Mutations
Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur
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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation
Procedia PDF Downloads 9832138 Study of the Antimicrobial Potential Of a Rich Polyphenolic Extract Obtained from Cytisus scoparius
Authors: Lorena G. Calvo, Marta Lores, Trinidad de Miguel
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Natural extracts containing high polyphenolic concentration possess antibacterial and antifungal activity. The present research characterizes a hydro-organic extract with a high polyphenolic content as an antimicrobial candidate. As a result of this composition, the extract showed pronounced bioactivities with potential uses in agricultural, veterinary, pharmaceutical, and cosmetic industries. Polyphenol compounds were extracted by using hydro-organic solvent mixtures from the shrub Cytisus scoparius. The in vitro antimicrobial activity of this extract was evaluated on Gram-positive and Gram-negative bacteria and the fungus Candida albicans. Microbial species investigated, Bacillus cereus, Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, are causing agents of several human and animal diseases. The extract showed activity against all tested species. So, it could be used for the development of biocides to control a wide range of pathogenic agents and contribute to the creation of economic and eco-friendly alternatives to antibiotics.Keywords: antimicrobial properties, antioxidant properties, Cytisus scoparius, polyphenolic extract
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