Search results for: myelin basic protein

Authors: Sehrish Ather

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Introduction: To improve organizational achievements through the production of new knowledge, health policy and system research is the basic requirement. An aging population is always the source of the increased burden of chronic diseases, disabilities, mental illnesses, and other co-morbidities; therefore the provision of quality health care services to every group of the population should be achieved by making strong policy and system research for the betterment of health care system. Unfortunately, the whole world is lacking policies and system research for providing health care to their elderly population. Materials and Methods: A literature review of published studies on aging diseases was done, ranging from the year 2011-2018. Geriatric, population, health policy, system, and research were the key terms used for the search. Databases searched were Google Scholar, PubMed, Science Direct, Ovid, and Research Gate. Grey literature was searched from various websites, including IHME, Library of the University of Lahore, World Health Organization (Ageing and Life Course), and Personal communication with Neuro-physicians. After careful reviewing published and un-published information, it was decided to carry on with commentary. Results and discussion: Most of the published studies have highlighted the need to advocate the funders of health policy and stakeholders of healthcare system research, and it was detected as a major issue, research on policy and healthcare system to provide health care to 'geriatric population' was found as highly neglected area. Conclusion: It is concluded that physicians are more involved with the policy and system research regarding any type of diseases, but scientists and researchers of basic and social science are less likely to be involved in methods used for health policy and system research due to lack of funding and resources. Therefore ageing diseases should be considered as a priority, and comprehensive policy and system research should be initiated for diseases of the geriatric population.

Keywords: geriatric population, health care system, health policy, system research

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Authors: F. Alaa Ali, S. A. Sherein Abdelgayed, S. Osama. EL-Tawil, M. Adel Bakeer

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Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD₅₀) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.

Keywords: albino rats, tartrazine, toxicity, pathology

Procedia PDF Downloads 341

Authors: Anna Martin, Raffael Osen

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The demand for fish from aquaculture is constantly growing. Concurrently, due to a shortage of fishmeal caused by extensive overfishing, fishmeal substitution by plant proteins is getting increasingly important for the production of sustainable aquafeed. Several research studies evaluated the impact of plant protein meals, concentrates or isolates on fish health and fish feed quality. However, these protein raw materials often require elaborate and expensive manufacturing and their availability is limited. Rapeseed press cake (RPC) – a side product of de-oiling processes – exhibits a high potential as a plant-based fishmeal alternative in fish feed for carnivorous species due to its availability, low costs and protein content. In order to produce aquafeed with RPC, it is important to systematically assess i) inclusion levels of RPC with similar pellet qualities compared to fishmeal containing formulations and ii) how extrusion parameters can be adjusted to achieve targeted pellet qualities. However, the effect of RPC on extrusion system parameters and pellet quality has only scarcely been investigated. Therefore, the aim of this study was to evaluate the impact of feed formulation, extruder barrel temperature (90, 100, 110 °C) and screw speed (200, 300, 400 rpm) on extrusion system parameters and the physical properties of fish feed pellets. A co-rotating pilot-scale twin screw extruder was used to produce five iso-nitrogenous feed formulations: a fish meal based reference formulation including 16 g/100g fishmeal and four formulations in which fishmeal was substituted by RPC to 25, 50, 75 or 100 %. Extrusion system parameters, being product temperature, pressure at the die, specific mechanical energy (SME) and torque, were monitored while samples were taken. After drying, pellets were analyzed regarding to optical appearance, sectional and longitudinal expansion, sinking velocity, bulk density, water stability, durability and specific hardness. In our study, the addition of minor amounts of RPC already had high impact on pellet quality parameters, especially on expansion but only marginally affected extrusion system parameters. Increasing amounts of RPC reduced sectional expansion, sinking velocity, bulk density and specific hardness and increased longitudinal expansion compared to a reference formulation without RPC. Water stability and durability were almost not affected by RPC addition. Moreover, pellets with rapeseed components showed a more coarse structure than pellets containing only fishmeal. When the adjustment of barrel temperature and screw speed was investigated, it could be seen that the increase of extruder barrel temperature led to a slight decrease of SME and die pressure and an increased sectional expansion of the reference pellets but did almost not affect rapeseed containing fish feed pellets. Also changes in screw speed had little effects on the physical properties of pellets however with raised screw speed the SME and the product temperature increased. In summary, a one-to-one substitution of fishmeal with RPC without the adjustment of extrusion process parameters does not result in fish feed of a designated quality. Therefore, a deeper knowledge of raw materials and their behavior under thermal and mechanical stresses as applied during extrusion is required.

Keywords: extrusion, fish feed, press cake, rapeseed

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Authors: F. A. Adesoji, A. A. Ayandele

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There has been a concern over non-responsiveness of educational programme in Nigeria’s higher institutions to adequately meet social needs. The study, therefore, investigated the effectiveness of basic elements of the Social Studies Curriculum, the contributions of the Teacher–Related Variables (TRV) such as qualification, area of specialization, teaching experience, teaching methods, gender and teaching facilities to the implementation of the curriculum (IOC) in the Colleges of Education (COEs). The study adopted the descriptive survey design. Four COEs in Oyo, Osun, Ondo and Lagos States were purposively selected. Stratified sampling technique was used to select 455 Social Studies students and 47 Social Studies lecturers. Stakeholders’ Perception of Social Studies Curriculum (r = 0.86), Social Studies Curriculum Resources scale (r = 0.78) and Social Studies Basic Concepts Test (r = 0.78) were used for data collection. Data were analysed using descriptive statistics, multiple regression, and t-test at 0.05 level of significance. COEs teachers and students rated the elements of the curriculum to be effective with mean scores x̄ =3.02 and x̄ =2.80 respectively; x̄ =5.00 and x̄ = 2.50 being the maximum and minimum mean scores. The finding showed average level of availability (x̄ =1.60), adequacy (x̄ =1.55) and utilization (x̄ =1.64) of teaching materials, x̄ =3.00 and x̄ =1.50 being maximum and minimum mean scores respectively. Academic performance of the students is on average with the mean score of x̄ =51.4775 out of maximum mean score of x̄ =100. The TRV and teaching facilities had significant composite contribution to IOC (F (6,45) = 3.92:R² = 0.26) with 39% contributions to the variance of IOC. Area of specialization (β= 29, t = 2.05) and teaching facilities (β = -25, t = 1.181) contributed significantly. The implementation of bachelor degree in Social Studies curriculum was effective in the colleges of education. There is the need to beef-up the provision of facilities to improve the implementation of the curriculum.

Keywords: bachelor degree in social studies, colleges of education in southwestern Nigeria, curriculum implementation, social studies curriculum

Procedia PDF Downloads 375

Authors: Adegoke Yinka Adebayo

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An understanding of the critical product attributes that impact on in vivo performance is key to the production of safe and effective medicines. Thus, a key driver for our research is the development of new basic science and technology underpinning the development of new pharmaceutical products. Research includes the structure and properties of drugs and excipients, biopharmaceutical characterisation, pharmaceutical processing and technology and formulation and analysis.

Keywords: drug discovery, drug development, drug delivery

Procedia PDF Downloads 481

Authors: Shuji Fujimoto, Fumiko Kojima, Mika Shigematsu

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Biorisk management (Biosafety/Biosecurity) is required for anyone working in a clinical laboratory (including medical/clinical research laboratories) where infectious agents and potentially hazardous biological materials are examined/stored. Proper education and training based on international standards of biorisk management should be provided not only as a part of laboratory safety program in work place but also as a part of introductory training at educational institutions for continuity and to elevate overall baseline of the biorisk management. We reported results of the pilot study of biorisk management education for graduate students majored in laboratory diagnostics previously. However, postgraduate education is still late in their profession and the participants’ interview also revealed importance and demands of earlier biorisk management education for undergraduates. The aim of this study is to identify the need for biosafety/biosecurity education and training program which is designed for undergraduate students who are entering the profession in clinical microbiology. We modified the previous program to include more basic topics and explanations (risk management, principles of safe clinical lab practices, personal protective equipment, disinfection, disposal of biological substances) and provided incorporating in the routine educational system for faculty of medical sciences in Kyushu University. The results of the pre and post examinations showed that the knowledge of the students on biorisk control had developed effectively as a proof of effectiveness of the program even in the undergraduate students. Our study indicates that administrating the basic biorisk management program in the earlier stage of learning will add positive impact to the understanding of biosafety to the health professional education.

Keywords: biorisk management, biosafety, biosecurity, clinical microbiology, education for undergraduates

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

Procedia PDF Downloads 271

Authors: Sonia Hirt

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The Planner's Triangle, an oft-cited model that visually defined planning as the search for sustainability to balance the three basic priorities of equity, economy, and environment, has influenced planning theory and practice for a quarter of a century. In this essay, we argue that the triangle requires updating and expansion. Even if planners keep sustainability as their key core aspiration at the center of their imaginary geometry, the triangle's vertices have to be rethought. Planners should move on to a 21st-century concept. We propose a Planner's Pentangle with five basic priorities as vertices of a new conceptual polygon. These five priorities are Wellbeing, Equity, Economy, Environment, and Esthetics (WE⁴). The WE⁴ concept more accurately and fully represents planning’s history. This is especially true in the United States, where public art and public health played pivotal roles in the establishment of the profession in the late 19th and early 20th centuries. It also more accurately represents planning’s future. Both health/wellness and aesthetic concerns are becoming increasingly important in the 21st century. The pentangle can become an effective tool for understanding and visualizing planning's history and present. Planning has a long history of representing urban presents and future as conceptual models in visual form. Such models can play an important role in understanding and shaping practice. For over two decades, one such model, the Planner's Triangle, stood apart as the expression of planning's pursuit for sustainability. But if the model is outdated and insufficiently robust, it can diminish our understanding of planning practice, as well as the appreciation of the profession among non-planners. Thus, we argue for a new conceptual model of what planners do.

Keywords: sustainable development, planning for sustainable development, planner's triangle, planner's pentangle, planning and health, planning and art, planning history

Procedia PDF Downloads 125

Authors: O. J. Osunkeye, P. O. Fakolade, B. E. Olorede

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Broilers productions depend on the provision of adequate and goo quality feed containing all the nutrients, including proteins, carbohydrate, fats, vitamins, minerals and water. All these nutrients have to be provided at a required amount to support maximum productivity and normal physiological functions and demands. Among these nutrients proteins are particularly important, since they are essential for meat and muscle production, optimum growth and health status. Poultry production industry in the developing countries is been threatened because of the over dependency on Soybean meal as one of the key/major conventional protein stuff for feeding livestock. Even the competition between man and livestock for Soybean and other protein sources made the price of this feed stuff to be on the increase. Hence the needs to seek for an alternative feed stuff which is cheap and less competitive. This study showed the blood profile, organ and carcass characteristics and performance of broilers fed with Cowpea Testa Meal (CTM) based diets. Four diets were formulated with Cowpea Testa replacing Soybean at 0%, 15%, 30%, and 50% graded levels. One hundred and twenty day-old unsexed broiler birds were allotted to these four treatments with 3 replicates of 10 birds per replicate. The results showed no significant differences in all the haematological parameters measured (P>0.05), the serum metabolites analysis revealed significant different in Cholesterol (99.8 mg/dl, 112.84 mg/dl, 131.07 mg/dl and 97.66 mg/dl respectively) (P<0.05) among others. There were significant differences within the diets for average daily weight gain, average feed intake and feed to gain ratio. The birds on control (0%) and CTM gained more weight than those fed with 30% and 50% CTM diets. The organs and carcass primal cuts of the broilers expressed significant different for the spleen (0.12 g, 0.09 g, 0.11 g and 0.14 g respectively), lungs (0.97 g, 0.72 g, 0.77 g and 1.01g respectively) and proventriculus (0.96 g, 0.99 g, 0.81 g and 0.85 g respectively) (P<0.05). For the carcass, there were no significant differences (P<0.05) in the breast, thigh, drumstick, wing and neck except for the Back (21.27 g, 21.04 g, 17.71 g, and 17.89 g respectively). In conclusion, CTM inclusion in broiler’s diet could be used as an alternative feed stuff in replacement of Soybean meal up to 15% without any adverse effects as revealed by the blood profile and to increase the growth performance of the birds.

Keywords: physiological functions, cholesterol, blood profiles, CTM and carcass analysis

Procedia PDF Downloads 598

Authors: I. A. Yola

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Impact of poultry dropping, cow dung and rumen content on utilization and proximate composition of Oreochromis niliticus, Clarias gariepinus and Cyprinus capio in a polyculture system were studied. The research was conducted over a period of 52 weeks. Poultry droppings (PD), cow dung (CD) and rumen content (RC) were applied at three levels 30g,60g and 120g/m2/week, 25g,50g and 100g/m2/week and 22g, 44g and 88g/m2/week treatment, respectively. The control only conventional feed with 40% CP without manure application was used. Physicochemical and biological properties measured were higher in manure pond than control. The difference was statistically significant (P < 0.05) between and within treatments with exception of temperature with a combined mean of 27.900C. The water was consistently alkaline with mean values for pH of 6.61, transparency 22.6cm, conductivity 35.00µhos/cm, dissolved oxygen 4.6 mg/l, biological oxygen demand 2.8mg/l, nitrate and phosphates 0.9mg/l and 0.35mg/l, respectively. The three fish species increase in weight with increased manure rate, with a higher value in PD treatment on C. capio record 340g, O. niloticus weighed 310g and C. gariepinus 280g over the experimental period. Fishes fed supplementary diet (control) grew bigger with highest value on C. capio (685g) O. niloticus (620g) and then C. gariepinus (526g). The differences were statistically significant (P < 0.05). The result of whole body proximate analysis indicated that various manures and rates had an irregular pattern on the protein and ash gain per 100g of fish body weight gain. The combined means for whole fish carcass protein, lipids, moisture, ash and gross energy were 11.84, 2.43, 74.63, 3.00 and 109.9 respectively. The notable exceptions were significant (p < 0.05) increases in body fat and gross energy gains in all fish species accompanied by decreases in percentages of moisture as manure rates increased. Survival percentage decreases from 80% to 70%. It is recommended to use poultry dropping as manure/feeds at the rate of 120kg/ha/week for good performances in polyculture.

Keywords: organic manure, Nile tilapia, African mud fish, common carp, proximate composition

Procedia PDF Downloads 540

Authors: Yu Yoshihara, Chika Tada, Moe Takada, Nyam-Osor Purevdorj, Khorolmaa Chimedtseren, Yutaka Nakai

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Water pollution from animal waste and its influence on grazing animals is a current concern regarding Mongolian grazing lands. We allocated 32 free-grazing lambs to four groups and provided each with water from a different source (upper stream, lower stream, well, and pond) for 49 days. We recorded the amount of water consumed by the lambs, as well as their body weight, behavior, white blood cell count, acute phase (haptoglobin) protein level, and fecal condition. We measured the chemical and biological qualities of the four types of water, and we detected enteropathogenic and enterohemorrhagic Escherichia coli in fecal samples by using a genetic approach. Pond water contained high levels of nitrogen and minerals, and well water contained high levels of bacteria. The odor concentration index decreased in order from pond water to upper stream, lower stream, and well. On day 15 of the experiment, the following parameters were the highest in lambs drinking water from the following sources: water intake (pond or lower stream), body weight gain (pond), WBC count (lower stream), haptoglobin concentration (well), and enteropathogenic E. coli infection rate (lower stream). Lambs that drank well water spent more time lying down and less time grazing than the others, and lambs that drank pond water spent more time standing and less time lying down. Lambs given upper or lower stream water exhibited more severe diarrhea on day 15 of the experiment than before the experiment. Mongolian sheep seemed to adapt to chemically contaminated water: their productivity benefited the most from pond water, likely owing to its rich mineral content. Lambs that drank lower stream water showed increases in enteropathogenic E. coli infection, clinical diarrhea, and WBC count. Lambs that drank well water, which was bacteriologically contaminated, had increased serum acute phase protein levels and poor physical condition; they were thus at increased risk of negative health and production effects.

Keywords: DNA, Escherichia coli, fecal sample, lower stream, well water

Procedia PDF Downloads 454

Authors: Jeong-Min Son, Jeong-Hee Eum, Jin-Kyu Min, Uk-Je Sung, Ju-Eun Kim

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While various environmental problems are severe due to climate change, especially in cities where population and development are concentrated, urban thermal environment problems such as heat waves and tropical nights are particularly worsening. Accordingly, the Korean government provides basic data related to the urban thermal environment to support each local government in effectively establishing policies to cope with heat waves. However, the basic data related to the thermal environment provided by the government has limitations in establishing a regional thermal adaptation plan with a minimum unit of cities, counties, and districts. In addition, the urban heat environment perceived by people differs in each region and space. Therefore, it is necessary to prepare practical measures that can be used to establish regional-based policies for heat wave adaptation by identifying people’s heat perception in the entire city. This study aims to develop a mobile phone application (APP) to gather people’s thermal sensation information and create Korea’s first thermal map based on this information. In addition, through this APP, citizens directly propose thermal adaptation policies, and urban planners and policymakers accept citizens' opinions, so this study provides a tool to solve local thermal environment problems. To achieve this purpose, first, the composition and contents of the app were discussed by examining various existing apps and cases for citizen participation and collection of heat information. In addition, factors affecting human thermal comfort, such as spatial, meteorological, and demographic factors, were investigated to construct the APP system. Based on these results, the basic version of the APP was developed. Second, the living lab methodology was adopted to gather people’s heat perception using the developed app to conduct overall evaluation and feedback of people on the APP. The people participating in the living lab were selected as those living in Daegu Metropolitan City, which is located in South Korea and annually records high temperatures. The user interface was improved through the living lab to make the app easier to use and the thermal map was modified. This study expects to establish high-resolution thermal maps for effective policies and measures and to solve local thermal environmental problems using the APP. The collected information can be used to evaluate spatial, meteorological, and demographic characteristics that affect the perceived heat of citizens. In addition, it is expected that the research can be expanded by gathering thermal information perceived by citizens of foreign cities as well as other cities in South Korea through the APP developed in this study.

Keywords: mobile application, living lab, thermal map, climate change adaptation

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Authors: Sima Majnooni

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This paper discusses the Green Climate Fund's environmental and social management framework (GCF). The environmental and social management framework ensures the accredited entity considers the GCF's accreditation standards and effectively implements each of the GCF-funded projects. The GCF requires all accredited entities to meet basic transparency and accountability standards as well as environmental and social safeguards (ESMS). In doing so, the accredited entity sets up different independent units. One of these units is called the Grievance Mechanism. When allegations of environmental and social harms are raised in association with GCF-funded activities, affected parties can contact the entity’s grievance unit. One of the most challenging things about the accredited entity's grievance unit is the lack of available information and resources on the entities' websites. Many AEs have anti-corruption or anti-money laundering unit, but they do not have the environmental and social unit for affected people. This paper will argue the effectiveness of environmental and social grievance mechanisms of AEs by using a qualitative approach to indicate how many of AEs have a poor or an effective GRM. Some ESMSs seem highly effective. On the other hand, other mechanisms lack basic requirements such as a clear, transparent, uniform procedure and a definitive timetable. We have looked at each AE mechanism not only in light of how the website goes into detail regarding the process of grievance mechanism but also in light of their risk category. Many mechanisms appear inadequate for the lower level risk category entities (C) and, even surprisingly, for many higher-risk categories (A). We found; in most cases, the grievance mechanism of AEs seems vague.

Keywords: grievance mechanism, vague environmental and social policies, green climate fund, international climate finance, lower and higher risk category

Procedia PDF Downloads 111

Authors: Cangir Uyarlar, Ismail Bayram, Ibrahim Sadi Cetingul, Mustafa Kabu, Eyup Eren Gultepe

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This study was conducted to determine the effects of organic chromium and organic chromium+propylene glycol on milk yield and some blood parameters related with liver fatty acid metabolism in early lactation dairy cows. Thirty multiparous Holstein dairy cows were used as study material. Cows assigned to three groups as control (C), chromium (Cr) and chromium+propylene glycol (CP). Live weight, parity and body condition score were used as covariates for statistical analyses. The study began at calving and finished at 3 weeks after calving. All cows were consumed same diet. Organic chromium and organic chromium+propylene glycol were orally administrated to cows in treatment groups shortly after the morning milking. Blood samples were collected from all cows on 0 (calving), 3rd, 6th, 9th, 12th, 15th, 18th, 21th days after calving. Then, samples were analyzed for BHBA (Betahydroxybutiric acids), NEFA (Non Esterified Fatty Acids), urea, total protein (TP) and glucose concentrations. Weekly milk yields were calculated from daily milk data on farm. Organic chromium treatment had no significant differences on serum biochemical parameters and milk yields. However, administration of organic chromium and propylene glycol combination decreased serum urea and total protein concentration, helped to protection from subclinical metabolic diseases via decreasing serum NEFA and BHBA concentrations. Also, this combination decreased serum glucose levels of cows. Neither only chromium nor chromium and propylene glycol combination did not affect milk yield throughout the study. These findings were suggested that orally administrations of chromium and propylene glycol combination improved liver glucose and fatty acid metabolism, decreased serum parameters which are representing subclinical diseases in early lactation dairy cows.

Keywords: chromium, early lactation dairy cows, propylene glycol, milk yield

Procedia PDF Downloads 474

Authors: Salah Belaidi

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We have carried out extensive and in-depth research to search for bioactive compounds based on Algerian plants. A selection of 50 ligands from Algerian medicinal plants. Several compounds used in herbal medicine have been drawn using Marvin Sketch software. We determined the three-dimensional structures of the ligands with the MMFF94 force field in order to prepare these ligands for molecular docking. The 3D protein structure of the SARS-CoV-2 main protease was taken from the Protein Data Bank. We used AutoDockVina software to apply molecular docking. The hydrogen atoms were added during the molecular docking process, and all the twist bonds of the ligands were added using the (ligand) module in the AutoDock software. The COVID-19 main protease (Mpro) is a key enzyme that plays a vital role in viral transcription and mediating replication, so it is a very attractive drug target for SARS-CoV-2. In this work, an evaluation was carried out on the biologically active compounds present in these selected medicinal plants as effective inhibitors of the protease enzyme of COVID-19, with an in-depth computational calculation of the molecular docking using the Autodock Vina software. The top 7 ligands: Phloroglucinol, Afzelin, Myricetin-3-O- rutinosidTricin 7-neohesperidoside, Silybin, Silychristinthat and Kaempferol are selected among the 50 molecules studied which are Algerian medicinal plants, whose selection is based on the best binding energy which is relatively low compared to the reference molecule with binding affinities of -9.3, -9.3, -9, -8.9, -8 .5, 8.3 and -8.3 kcal mol-1 respectively. Then, we analyzed the ADME properties of the best7 ligands using the web server SwissADME. Two ligands (Silybin, Silychristin) were found to be potential candidates for the discovery and design of novel drug inhibitors of the protease enzyme of SARS-CoV-2. The stability of the two ligands in complexing with the Mpro protease was validated by molecular dynamics simulation; they revealed a stable trajectory in both techniques, RMSD and RMSF, by showing molecular properties with coherent interactions in molecular dynamics simulations. Finally, we conclude that the Silybin ligand forms a more stable complex with the Mpro protease compared to the Silychristin ligand.

Keywords: COVID-19, medicinal plants, molecular docking, ADME properties, molecular dynamics

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Authors: Cemil Kutluturk

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This is a comparative study of the incarnation of God according to Hinduism and Christianity. After dealing with their basic ideas on the concept of the incarnation of God, the main similarities and differences between each other will be examined by quoting references from their sacred texts. In Hinduism, the term avatara is used in order to indicate the concept of the incarnation of God. The word avatara is derived from ava (down) and tri (to cross, to save, attain). Thus avatara means to come down or to descend. Although an avatara is commonly considered as an appearance of any deity on earth, the term refers particularly to descents of Vishnu. According to Hinduism, God becomes an avatara in every age and entering into diverse wombs for the sake of establishing righteousness. On the Christian side, the word incarnation means enfleshment. In Christianity, it is believed that the Logos or Word, the Second Person of Trinity, presumed human reality. Incarnation refers both to the act of God becoming a human being and to the result of his action, namely the permanent union of the divine and human natures in the one Person of the Word. When the doctrines of incarnation and avatara are compared some similarities and differences can be found between each other. The basic similarity is that both doctrines are not bound by the laws of nature as human beings are. They reveal God’s personal love and concern, and emphasize loving devotion. Their entry into the world is generally accompanied by extraordinary signs. In both cases, the descent of God allows for human beings to ascend to God. On the other hand, there are some distinctions between two religious traditions. For instance, according to Hinduism there are many and repeated avataras, while Christ comes only once. Indeed, this is related to the respective cyclic and linear worldviews of the two religions. Another difference is that in Hinduism avataras are real and perfect, while in Christianity Christ is also real, yet imperfect; that is, he has human imperfections, except sin. While Christ has never been thought of as a partial incarnation, in Hinduism there are some partial and full avataras. The other difference is that while the purpose of Christ is primarily ultimate salvation, not every avatara grants ultimate liberation, some of them come only to save a devotee from a specific predicament.

Keywords: Avatara, Christianity, Hinduism, incarnation

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Authors: D. Bäcker, H. Chaves

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The key to improve surface cleaning of the fouling is understanding of the mechanism of separation process of the deposit from the surface. The authors give basic principles of characterization of separation process and introduce a corresponding criterion. The developed criterion is a measure for the moment of separation of the deposit from the surface. For this purpose a new measurement technique is described.

Keywords: cleaning, fouling, separation, criterion

Procedia PDF Downloads 445

Authors: Hina Javed

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This study investigated the different strategies used by Pakistani students learning English as a second language at secondary level school. The basic premise of the study is that ESL students face tremendous difficulty while they are reading a text in English. It also purports to dig into the different causes of their slow reading. They might range from word reading accuracy, mental translation, lexical density, cultural gaps, complex syntactic constructions, and back skipping. Sixty Grade 7 students from two secondary mainstream schools in Lahore were selected for the study, thirty being boys and thirty girls. They were administered reading-related and reading speed pre and post-tests. The purpose of the tests was to gauge their performance on different reading tasks so as to be able to see how they used strategies, if any, and also to ascertain the causes hampering their performance on those tests. In the pretests, they were given simple texts with considerable lexical density and moderately complex sentential layout. In the post-tests, the reading tasks contained comic strips, texts with visuals, texts with controlled vocabulary, and an evenly distributed varied range of simple, compound, and complex sentences. Both the tests were timed. The results gleaned through the data gathered corroborated the researchers’ basic hunch that they performed significantly better than pretests. The findings suggest that the morphological structure of words and lexical density are the main sources of reading comprehension difficulties in poor ESL readers. It is also confirmed that if the texts are accompanied by pictorial visuals, it greatly facilitates students’ reading speed and comprehension. There is no substantial evidence that ESL readers adopt any specific strategy while reading in English.

Keywords: slow ESL reading speed, mental translation, complex syntactic constructions, back skipping

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Authors: Mohamed Moussaoui, Mouna Baassi, Soukayna Baammi, Hatim Soufi, Mohammed Salah, Rachid Daoud, Achraf EL Allali, Mohammed Elalaoui Belghiti, Said Belaaouad

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The present study aims to investigate the quantitative structure-activity relationship (QSAR) of a series of Thiazole derivatives reported as anticancer agents (hepatocellular carcinoma), using principally the electronic descriptors calculated by the density functional theory (DFT) method and by applying the multiple linear regression method. The developed model showed good statistical parameters (R²= 0.725, R²ₐ𝒹ⱼ= 0.653, MSE = 0.060, R²ₜₑₛₜ= 0.827, Q²𝒸ᵥ = 0.536). The energy of the highest occupied molecular orbital (EHOMO) orbital, electronic energy (TE), shape coefficient (I), number of rotatable bonds (NROT), and index of refraction (n) were revealed to be the main descriptors influencing the anti-cancer activity. Additional Thiazole derivatives were then designed and their activities and pharmacokinetic properties were predicted using the validated QSAR model. These designed molecules underwent evaluation through molecular docking (MD) and molecular dynamic (MD) simulations, with binding affinity calculated using the MMPBSA script according to a 100 ns simulation trajectory. This process aimed to study both their affinity and stability towards Cyclin-Dependent Kinase 2 (CDK2), a target protein for cancer disease treatment. The research concluded by identifying four CDK2 inhibitors - A1, A3, A5, and A6 - displaying satisfactory pharmacokinetic properties. MDs results indicated that the designed compound A5 remained stable in the active center of the CDK2 protein, suggesting its potential as an effective inhibitor for the treatment of hepatocellular carcinoma. The findings of this study could contribute significantly to the development of effective CDK2 inhibitors.

Keywords: QSAR, ADMET, Thiazole, anticancer, molecular docking, molecular dynamic simulations, MMPBSA calculation

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Authors: Fitria D. Ayuningtyas, Anggraini Barlian

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Green turtle (Chelonia mydas) is one of TSD (Temperature-dependent Sex Determination, TSD) animals which sex is determined by the egg’s incubation temperature. GSD (Genotypic Sex Determination) homologous genes such as Wilms’ Tumor (Wt1) and Forkhead Box L2 (FoxL2) play a role in TSD animal sex determination process. Wt1 plays a role in both male pathway, as a transcription factor for Sf1 gene and in female pathway, as a transcription factor for Dax1. FoxL2 plays a role specifically in female sex determination, and known as transcriptional factor for Aromatase gene. Until now, research on the pattern of Wt1 and FoxL2 genes expression in C.mydas has not been conducted yet. The aim of this research is to know the pattern of Wt1 and FoxL2 genes expression in Mesonephros-Gonad (MG) complexes of Chelonia mydas embryos incubated in masculinizing temperature (MT) and feminizing temperature (FT). Eggs of C.mydas incubated in 3 different stage of TSP (Thermosensitive Period) at masculinizing temperature (26±10C, MT) and feminizing temperature (31±10C FT). Mesonefros-gonad complexes were isolated at Pre-TSP stage (FT at days 14th, MT at days 24th), TSP stage (FT at days 24th, MT at days 36th) and differentiated stage (FT at days 40th, MT at days 58th). RNA from mesonephros-gonad (MG) complexes were converted into cDNA by RT-PCR process, and the pattern of Wt1 and FoxL2 genes expression is analyzed by quantitative Real Time PCR (qPCR) method, β-actin gene is used as an internal control. The pattern of Wt1 gene expression in Pre-TSP stage was almost the same between MG complexes incubated at MT or FT, while TSP and differentiation stage, the pattern of Wt1 gene expression in MG complexes incubated at MT or FT was increased. Wt1 gene expression of MG complexes that incubated at FT was higher than at MT. There was a difference pattern between Wt1 gene expression in this research compared to the previous research in protein level. It could be assumed that the difference caused by post-transcriptional regulation mechanisms before mRNA of Wt1 gene translated into protein structure. The pattern of FoxL2 gene expression in Pre-TSP stage was almost the same between MG complexes that incubated at MT and FT, and increased in both TSP and differentiated stage. The FoxL2 gene expression in MG complexes that incubated in FT is higher than MT on TSP and differentiated stage. Based on the results of this research, it can be assumed that Wt1 and FoxL2 gene were expressed in MG complexes that incubated both at MT and FT since Pre-TSP stage. The pattern of Wt1 gene expression was increased in every stage of gonadal development, and so do the pattern of FoxL2 gene expression. Wt1 and FoxL2 gene expressions were higher in MG complexes incubated at FT than MT.

Keywords: chelonia mydas, FoxL2, gene expression, TSD, Wt1

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Authors: Hamza Zidoum

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This paper investigates the impact of human genetic variation on the function of human proteins using machine-learning algorithms. Single-Nucleotide Polymorphism represents the most common form of human genome variation. We focus on the single amino-acid polymorphism located in the coding region as they can affect the protein function leading to pathologic phenotypic change. We use several supervised Machine Learning methods to identify structural properties correlated with increased risk of the missense mutation being damaging. SVM associated with Principal Component Analysis give the best performance.

Keywords: single-nucleotide polymorphism, machine learning, feature selection, SVM

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Authors: Leila Safazadeh, Brad Berron

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Self-assembled monolayers have tremendous impact in interfacial science, due to the unique opportunity they offer to tailor surface properties. Low-density self-assembled monolayers are an emerging class of monolayers where the environment-interfacing portion of the adsorbate has a greater level of conformational freedom when compared to traditional monolayer chemistries. This greater range of motion and increased spacing between surface-bound molecules offers new opportunities in tailoring adsorption phenomena in sensing systems. In particular, we expect low-density surfaces to offer a unique opportunity to intercalate surface bound ligands into the secondary structure of protiens and other macromolecules. Additionally, as many conventional sensing surfaces are built upon gold surfaces (SPR or QCM), these surfaces must be compatible with gold substrates. Here, we present the first stable method of generating low-density self assembled monolayer surfaces on gold for the analysis of their interactions with protein targets. Our approach is based on the 2:1 addition of thiol-yne chemistry to develop new classes of y-shaped adsorbates on gold, where the environment-interfacing group is spaced laterally from neighboring chemical groups. This technique involves an initial deposition of a crystalline monolayer of 1,10 decanedithiol on the gold substrate, followed by grafting of a low-packed monolayer on through a photoinitiated thiol-yne reaction in presence of light. Orthogonality of the thiol-yne chemistry (commonly referred to as a click chemistry) allows for preparation of low-density monolayers with variety of functional groups. To date, carboxyl, amine, alcohol, and alkyl terminated monolayers have been prepared using this core technology. Results from surface characterization techniques such as FTIR, contact angle goniometry and electrochemical impedance spectroscopy confirm the proposed low chain-chain interactions of the environment interfacing groups. Reductive desorption measurements suggest a higher stability for the click-LDMs compared to traditional SAMs, along with the equivalent packing density at the substrate interface, which confirms the proposed stability of the monolayer-gold interface. In addition, contact angle measurements change in the presence of an applied potential, supporting our description of a surface structure which allows the alkyl chains to freely orient themselves in response to different environments. We are studying the differences in protein adsorption phenomena between well packed and our loosely packed surfaces, and we expect this data will be ready to present at the GRC meeting. This work aims to contribute biotechnology science in the following manner: Molecularly imprinted polymers are a promising recognition mode with several advantages over natural antibodies in the recognition of small molecules. However, because of their bulk polymer structure, they are poorly suited for the rapid diffusion desired for recognition of proteins and other macromolecules. Molecularly imprinted monolayers are an emerging class of materials where the surface is imprinted, and there is not a bulk material to impede mass transfer. Further, the short distance between the binding site and the signal transduction material improves many modes of detection. My dissertation project is to develop a new chemistry for protein-imprinted self-assembled monolayers on gold, for incorporation into SPR sensors. Our unique contribution is the spatial imprinting of not only physical cues (seen in current imprinted monolayer techniques), but to also incorporate complementary chemical cues. This is accomplished through a photo-click grafting of preassembled ligands around a protein template. This conference is important for my development as a graduate student to broaden my appreciation of the sensor development beyond surface chemistry.

Keywords: low-density self-assembled monolayers, thiol-yne click reaction, molecular imprinting

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Authors: Martha Karunakar

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There exists a wide divide between the urban and the rural students in a vast country like India. This dichotomy is seen in the resources available to them, like the learning facilities, the infra-structure, the learning ambience and meeting of their basic needs of food, clothing and shelter. This paper discusses the effect of English language teaching as a Bridge course on a select batch of rural students at an Engineering college in Chennai, one of the four Metros of India. The study aims to understand how the teacher input and the teacher- peer-student interaction facilitates the acquisition of the basic structures of the English language to a group that is minimally exposed to the language. The objective in conducting the Bridge Course is to integrate these rural students into the mainstream and empower them in terms of English speaking ability; to enable them to comprehend their respective engineering classes where the medium of instruction is English and also to be able to interact with their urban peers. This program is conducted prior to the start of a regular academic session to equip them face the rigors of engineering education. The study is placed within the framework of Interaction theory in second language acquisition. The study evaluates the impact of linking theory and practice by implementing meaningful interaction not only within classrooms but also in the common areas. By providing intensive comprehensible input, it is anticipated that participant’s level of English language improves. The teaching methods and classroom activities included individual and group participation, encompassing all the four skills of listening, speaking, reading and writing (LSRW). The diagnostic tests that were administered before the commencement of the course and the exit test after the completion were used to record the impact of the training.

Keywords: comprehensible input, interaction, rural students, teaching English

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Authors: Rawa Delshada, Sanaa G. Hamab, Rastee D. Koyeec

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Eighty patients with suspected ischemic heart disease were enrolled in the present study. They were classified into two groups: patients with positive exercise stress test results (n=40) and control group with negative exercise stress test results (n=40). Serum concentration of troponin I, Heart-type Fatty Acid Binding Protein (H-FABP) and Ischemia Modified Albumin (IMA) were measured one hour after performing stress test. Enzyme Linked Immunosorbent Assay was used to measure both troponin I, H-FABP levels, while IMA levels were measured by albumin cobalt binding test. There was no statistically significant difference in the mean concentration of troponin I between two groups (0.75±0.55ng/ml) for patients with positive test result vs. (0.71±0.55ng/ml) for negative test result group with P>0.05. Contrary to our expectation, mean IMA level was slightly higher among control group (70.88±39.76U/ml) compared to (62.7±51.9U/ml) in positive test result group, but still with no statistically significant difference (P>0.05). Median H-FABP level was also higher among negative exercise stress testing group compared the positive one (2ng/ml vs. 1.9ng/ml respectively), but failed to reach statistically significant difference (P>0.05). When quartiles model used to explore the possible association between each study biomarkers with the others; serum H-FABP level was lowest (1.7ng/ml) in highest quartile of IMA and lowest H-FABP (1.8ng/ml) in highest quartile of troponin I but with no statistically significant association (P>0.05). Myocardial ischemia, more likely occurred after exercise stress test, is not capable of causing troponin I release. Furthermore, an increase in H-FABP and IMA levels after stress test are not reflecting myocardial ischemia. Moreover, the combination of troponin I, H-FABP and IMA after measuring their post exercise levels does not improve the diagnostic utility of exercise stress test enormously.

Keywords: cardiac biomarkers, ischemic heart disease, troponin I, ischemia modified albumin, heart-type fatty acid binding protein, exercise stress testing

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Authors: Liaqat Ali, Hubert E. Blum, Türkân Sakinc

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Enterococcus faecium is an emerging multidrug-resistant nosocomial pathogen increased dramatically worldwide and causing bacteremia, endocarditis, urinary tract and surgical site infections in immunocomprised patients. The capsular polysaccharides that contribute to pathogenesis through evasion of the host innate immune system are also involved in hindering leukocyte killing of enterococci. The gene cluster (enterococcal polysaccharide antigen) of E. faecalis encoding homologues of many genes involved in polysaccharide biosynthesis. We identified two putative loci with 22 kb and 19 kb which contained 11 genes encoding for glycosyltransferases (GTFs); this was confirmed by using genome comparison of already sequenced strains that has no homology to known capsule genes and the epa-locus. The polysaccharide-conjugate vaccines have rapidly emerged as a suitable strategy to combat different pathogenic bacteria, therefore, we investigated a polysaccharide biosynthesis CapD protein in E. faecium contains 336 amino acids and had putative function for N-linked glycosylation. The deletion/knock-out capD mutant was constructed and complemented by homologues recombination method and confirmed by using PCR and sequencing. For further characterization and functional analysis, in-vitro cell culture and in-vivo a mouse infection models were used. Our ΔcapD mutant shows a strong hydrophobicity and all strains exhibited biofilm production. Subsequently, the opsonic activity was tested in an opsonophagocytic assay which shows increased in mutant compared complemented and wild type strains but more than two fold decreased in colonization and adherence was seen on surface of uroepithelial cells. However, a significant higher bacterial colonialization was observed in capD mutant during animal bacteremia infection. Unlike other polysaccharides biosynthesis proteins, CapD does not seems to be a major virulence factor in enterococci but further experiments and attention is needed to clarify its function, exact mechanism and involvement in pathogenesis of enteroccocal nosocomial infections eventually to develop a vaccine/ or targeted therapy.

Keywords: E. faecium, pathogenesis, polysaccharides, biofilm formation

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Authors: M. A. Fiidow, Ahmad M. Alenezi

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In this work, we study the inner derivations of diassociative algebras in dimension two and three, an algorithmic approach is adopted for the computation of inner derivation, using some results from the derivation of finite dimensional diassociative algebras. Some basic properties of inner derivation of finite dimensional diassociative algebras are also provided.

Keywords: diassociative algebras, inner derivations, derivations, left and right operator

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Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

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Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

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Authors: Ebru Ozgur Guler, Huseyin Guler, Sera Sanli

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Social Progress Index (SPI) whose fundamentals have been thrown in the World Economy Forum is an index which aims to form a systematic basis for guiding strategy for inclusive growth which requires achieving both economic and social progress. In this research, it has been aimed to determine the relations among “Basic Human Needs” (BHN) (including four variables of ‘Nutrition and Basic Medical Care’, ‘Water and Sanitation’, ‘Shelter’ and ‘Personal Safety’) and “Opportunity” (OPT) (that is composed of ‘Personal Rights’, ‘Personal Freedom and Choice’, ‘Tolerance and Inclusion’, and ‘Access to Advanced Education’ components) dimensions of 2016 SPI for 138 countries which take place in the website of Social Progress Imperative by carrying out canonical correlation analysis (CCA) which is a data reduction technique that operates in a way to maximize the correlation between two variable sets. In the interpretation of results, the first pair of canonical variates pointing to the highest canonical correlation has been taken into account. The first canonical correlation coefficient has been found as 0.880 indicating to the high relationship between BHN and OPT variable sets. Wilk’s Lambda statistic has revealed that an overall effect of 0.809 is highly large for the full model in order to be counted as statistically significant (with a p-value of 0.000). According to the standardized canonical coefficients, the largest contribution to BHN set of variables has come from ‘shelter’ variable. The most effective variable in OPT set has been detected to be ‘access to advanced education’. Findings based on canonical loadings have also confirmed these results with respect to the contributions to the first canonical variates. When canonical cross loadings (structure coefficients) are examined, for the first pair of canonical variates, the largest contributions have been provided by ‘shelter’ and ‘access to advanced education’ variables. Since the signs for structure coefficients have been found to be negative for all variables; all OPT set of variables are positively related to all of the BHN set of variables. In case canonical communality coefficients which are the sum of the squares of structure coefficients across all interpretable functions are taken as the basis; amongst all variables, ‘personal rights’ and ‘tolerance and inclusion’ variables can be said not to be useful in the model with 0.318721 and 0.341722 coefficients respectively. On the other hand, while redundancy index for BHN set has been found to be 0.615; OPT set has a lower redundancy index with 0.475. High redundancy implies high ability for predictability. The proportion of the total variation in BHN set of variables that is explained by all of the opposite canonical variates has been calculated as 63% and finally, the proportion of the total variation in OPT set that is explained by all of the canonical variables in BHN set has been determined as 50.4% and a large part of this proportion belongs to the first pair. The results suggest that there is a high and statistically significant relationship between BHN and OPT. This relationship is generally accounted by ‘shelter’ and ‘access to advanced education’.

Keywords: canonical communality coefficient, canonical correlation analysis, redundancy index, social progress index

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Authors: Vaishali Patil, Neeraj Masand

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In older people, Alzheimer’s disease (AD) is turning out to be a lethal disease. According to the amyloid hypothesis, aggregation of the amyloid β–protein (Aβ), particularly its 42-residue variant (Aβ42), plays direct role in the pathogenesis of AD. Aβ is generated through sequential cleavage of amyloid precursor protein (APP) by β–secretase (BACE) and γ–secretase (GS). Thus in the treatment of AD, γ-secretase modulators (GSMs) are potential disease-modifying as they selectively lower pathogenic Aβ42 levels by shifting the enzyme cleavage sites without inhibiting γ–secretase activity. This possibly avoids known adverse effects observed with complete inhibition of the enzyme complex. Virtual screening, via drug-like ADMET filter, QSAR and molecular docking analyses, has been utilized to identify novel γ–secretase modulators with sulphonamide nucleus. Based on QSAR analyses and docking score, some novel analogs have been synthesized. The results obtained by in silico studies have been validated by performing in vivo analysis. In the first step, behavioral assessment has been carried out using Scopolamine induced amnesia methodology. Later the same series has been evaluated for neuroprotective potential against the oxidative stress induced by Scopolamine. Biochemical estimation was performed to evaluate the changes in biochemical markers of Alzheimer’s disease such as lipid peroxidation (LPO), Glutathione reductase (GSH), and Catalase. The Scopolamine induced amnesia model has shown increased Acetylcholinesterase (AChE) levels and the inhibitory effect of test compounds in the brain AChE levels have been evaluated. In all the studies Donapezil (Dose: 50µg/kg) has been used as reference drug. The reduced AChE activity is shown by compounds 3f, 3c, and 3e. In the later stage, the most potent compounds have been evaluated for Aβ42 inhibitory profile. It can be hypothesized that this series of alkyl-aryl sulphonamides exhibit anti-AD activity by inhibition of Acetylcholinesterase (AChE) enzyme as well as inhibition of plaque formation on prolong dosage along with neuroprotection from oxidative stress.

Keywords: gamma-secretase inhibitors, Alzzheimer's disease, sulphonamides, QSAR

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