Search results for: whey protein concentrate
1193 Stimulation of Nerve Tissue Differentiation and Development Using Scaffold-Based Cell Culture in Bioreactors
Authors: Simon Grossemy, Peggy P. Y. Chan, Pauline M. Doran
Abstract:
Nerve tissue engineering is the main field of research aimed at finding an alternative to autografts as a treatment for nerve injuries. Scaffolds are used as a support to enhance nerve regeneration. In order to successfully design novel scaffolds and in vitro cell culture systems, a deep understanding of the factors affecting nerve regeneration processes is needed. Physical and biological parameters associated with the culture environment have been identified as potentially influential in nerve cell differentiation, including electrical stimulation, exposure to extracellular-matrix (ECM) proteins, dynamic medium conditions and co-culture with glial cells. The mechanisms involved in driving the cell to differentiation in the presence of these factors are poorly understood; the complexity of each of them raises the possibility that they may strongly influence each other. Some questions that arise in investigating nerve regeneration include: What are the best protein coatings to promote neural cell attachment? Is the scaffold design suitable for providing all the required factors combined? What is the influence of dynamic stimulation on cell viability and differentiation? In order to study these effects, scaffolds adaptable to bioreactor culture conditions were designed to allow electrical stimulation of cells exposed to ECM proteins, all within a dynamic medium environment. Gold coatings were used to make the surface of viscose rayon microfiber scaffolds (VRMS) conductive, and poly-L-lysine (PLL) and laminin (LN) surface coatings were used to mimic the ECM environment and allow the attachment of rat PC12 neural cells. The robustness of the coatings was analyzed by surface resistivity measurements, scanning electron microscope (SEM) observation and immunocytochemistry. Cell attachment to protein coatings of PLL, LN and PLL+LN was studied using DNA quantification with Hoechst. The double coating of PLL+LN was selected based on high levels of PC12 cell attachment and the reported advantages of laminin for neural differentiation. The underlying gold coatings were shown to be biocompatible using cell proliferation and live/dead staining assays. Coatings exhibiting stable properties over time under dynamic fluid conditions were developed; indeed, cell attachment and the conductive power of the scaffolds were maintained over 2 weeks of bioreactor operation. These scaffolds are promising research tools for understanding complex neural cell behavior. They have been used to investigate major factors in the physical culture environment that affect nerve cell viability and differentiation, including electrical stimulation, bioreactor hydrodynamic conditions, and combinations of these parameters. The cell and tissue differentiation response was evaluated using DNA quantification, immunocytochemistry, RT-qPCR and functional analyses.Keywords: bioreactor, electrical stimulation, nerve differentiation, PC12 cells, scaffold
Procedia PDF Downloads 2421192 Association of Xeroderma pigmentosum Group D Gene Polymorphism with Colorectal Cancer Risk in Kashmiri Population
Authors: Syed Sameer Aga, Saniya Nissar
Abstract:
The Xeroderma pigmentosum group D gene (XPD) plays a key role in nucleotide excision repair (NER) pathway of the damaged DNA. Genetic polymorphisms in the coding region of the XPD gene may alter DNA repair capacity of the protein and hence can modulate the risk of colorectal cancer (CRC) risk. The aim of the study was to determine the genetic association of XPD Lys751Gln polymorphism with the risk of colorectal cancer (CRC) development. 120 CRC patients and 160 normal controls were assessed for genotype frequencies of XPD Lys751Gln polymorphism using PCR-RFLP technique. We observed a significant association (p < 0.05) between the XPD Lys751Gln polymorphism and the risk of developing CRC (p < 0.05). Additionally, Gln/Gln genotype of the XPD gene doubled the risk for the development of CRC [p < 0.05; OR=2.25 95% CI (1.07-4.7)]. Our results suggest that there is a significant association between the XPD Lys751Gln polymorphism and the risk of CRC.Keywords: colorectal cancer, polymorphism, RFLP, DNA Repair, NER, XPD
Procedia PDF Downloads 2141191 The Decrease of Collagen or Mineral Affect the Fracture in the Turkey Long Bones
Authors: P. Vosynek, T. Návrat, M. Peč, J. Pořízka, P. Diviš
Abstract:
Changes of mechanical properties and response behavior of bones is an important external sign of medical problems like osteoporosis, bone remodeling after fracture or surgery, osteointegration, or bone tissue loss of astronauts in space. Measuring of mechanical behavior of bones in physiological and osteoporotic states, quantified by different degrees of protein (collagen) and mineral loss, is thus an important topic in biomechanical research. This contribution deals with the relation between mechanical properties of the turkey long bone–tibia in physiological, demineralized, and deproteinized state. Three methods for comparison were used: densitometry, three point bending and harmonic response analysis. The results help to find correlations between the methods and estimate their possible application in medical practice.Keywords: bone properties, long bone, osteoporosis, response behavior
Procedia PDF Downloads 4791190 China's Role in Promoting Regionalism in East Asia in Post-Maoist Era: An Analysis through Uneven and Combined Development
Authors: Ali Jibran
Abstract:
China was considered as a revisionist state by the countries of East Asia during Maoist era; but China’s role changed from a revisionist state to a constructive member of East Asian Community in post-Maoist era. This research will mainly investigate the two phenomena: what were reasons of behavioral change of China in East Asia and what role has China played to promote regionalism in East Asia since Open Door Policy of Deng Xiaoping. To understand these two phenomena, this study applies the international relations theory of Uneven and Combined Development (U&CD). The central finding of this study is that ‘whip of external necessity’ posed by the Western dominance during the Chinese ‘century of ignominy’ resulted in a Maoist regime in China in 1948 which was hostile to its neighbors due to ideological tensions. Maoist regime in China could not solve the challenges posed by the ‘international’; therefore after Mao’s death, a new economic approach was introduced in China to deal with the challenges postured by the ‘international’. Due to Deng Xiaoping’s 'Open Door Policy' era, China used its ‘privilege of historic backwardness’ and witnessed unprecedented economic growth. As the societies are multiple and exist in real time, therefore interaction among societies is pertinent. Export oriented domestic policy pushed China to concentrate less on class struggle and improve its relations with its neighbors in East Asia. As China soon become a global hub of trade after market oriented reforms, therefore friendly relations with the states of East Asia was pertinent. This study will investigate Chinese role in regionalism in East Asia in three area: Chinese role in promoting regionalism in East Asia, China’s role in economic integration in East Asia and China’s role in combatting terrorism in East Asia. This study will be divided in two section. The first section will deal with the transformation in Chinese behavior in East Asia in post Maoist era, and the second section will analyze China’s role in East Asia by looking at Chinese role in institutional mechanism, economic integration and combatting terrorism in East Asia.Keywords: East Asia, regionalism, institutionlism, economic integration
Procedia PDF Downloads 3751189 Construction of a Fusion Gene Carrying E10A and K5 with 2A Peptide-Linked by Using Overlap Extension PCR
Authors: Tiancheng Lan
Abstract:
E10A is a kind of replication-defective adenovirus which carries the human endostatin gene to inhibit the growth of tumors. Kringle 5(K5) has almost the same function as angiostatin to also inhibit the growth of tumors since they are all the byproduct of the proteolytic cleavage of plasminogen. Tumor size increasing can be suppressed because both of the endostatin and K5 can restrain the angiogenesis process. Therefore, in order to improve the treatment effect on tumor, 2A peptide is used to construct a fusion gene carrying both E10A and K5. Using 2A peptide is an ideal strategy when a fusion gene is expressed because it can avoid many problems during the expression of more than one kind of protein. The overlap extension PCR is also used to connect 2A peptide with E10A and K5. The final construction of fusion gene E10A-2A-K5 can provide a possible new method of the anti-angiogenesis treatment with a better expression performance.Keywords: E10A, Kringle 5, 2A peptide, overlap extension PCR
Procedia PDF Downloads 1491188 The Functionality of Ovarian Follicle on Steroid Hormone Secretion under Heat Stress
Authors: Petnamnueng Dettipponpong, Shuen E. Chen
Abstract:
Heat stress is known to have negative effects on reproductive functions, such as follicular development and ovulation. This study aimed to investigate the specific effects of heat stress on steroid hormone secretion of ovarian follicle cells, particularly in relation to the expression of Apolipoprotein B (ApoB) and microsomal triglyceride transfer protein (MTP). The aim of the study was to understand the impact of heat stress on steroid hormone secretion in ovarian follicle cells and to explore the role of ApoB and MTP in this process. Primary granulosa and theca cells were collected from follicles and cultured under heat stress conditions (42 °C) for various time periods. Controls were maintained under normal conditions (37.5 °C ). The culture medium was collected at different time points to measure levels of progesterone and estradiol using ELISA kits. ApoB and MTP expression levels were analyzed using homemade antibodies and western blot. Data were assessed by a one-way ANOVA comparison test with Duncan’s new multiple-range test. Results were expressed as mean±S.E. Difference was considered significant at P<0.05. The results showed that heat stress significantly increased progesterone secretion in granulosa cells, with the peak observed after 13 hours of recovery under thermoneutral conditions. Estradiol secretion by theca cells was not affected. Heat stress also had a significant negative effect on granulosa cell viability. Additionally, the expression of ApoB and MTP was found to be differentially regulated by heat stress. ApoB expression in theca cells was transiently promoted, while ApoB expression in granulosa cells was consistently suppressed. MTP expression increased after 5 hours of recovery in both cell types. These findings suggest a mechanism by which chicken follicle cells export cellular lipids as very low-density lipoprotein (VLDL) in response to thermal stress. These contribute to our understanding of the role of ApoB and MTP steroidogenesis and lipid metabolism under heat stress conditions. The study involved the collection of primary granulosa and theca cells, culture under different temperature conditions, and analysis of the culture medium for hormone levels using ELISA kits. ApoB and MTP expression levels were assessed using homemade antibodies and western blot. This study aimed to address the effects of heat stress on steroid hormone secretion in ovarian follicle cells, as well as the role of ApoB and MTP in this process. The study demonstrates that heat stress stimulates steroidogenesis in granulosa cells, affecting progesterone secretion. ApoB and MTP expression were found to be differentially regulated by heat stress, indicating a potential mechanism for the export of cellular lipids in response to thermal stress.Keywords: heat stress, granulosa cells, theca cells, steroidogenesis, chicken, apolipoprotein B, microsomal triglyceride transfer protein
Procedia PDF Downloads 731187 Hidden Truths of Advertising: An Unspoken Fact in Making Ethical Diffusions
Authors: Mustafa Hyder, Shamaila Burney, Roohi Mumtaz
Abstract:
The aim of this study is to determine the consequences of silent or hidden messages and their effectiveness in deteriorating or altering our ethical norms and values. The study also focuses the repercussions of subconscious messages and possibilities of ethical diffusion in our society. The research based on the question that what are the different factors that motivate advertisers to include subliminal messages and how much these unspoken truths affecting our ethical values silently. What are the causes and effects of the subliminal messages in general and the level of ethical diffusion and its acceptance? The concept of advertising is to promote and highlight the salient features of the products and services, a company offers. Advertising is the best option nowadays to convey the related information to the consumers so that they attracted more towards the products or services proposed. The other thing advertisers concentrate, is the psychological characteristics using to persuade consumers choice. Using skills and tactics of advertising to promote a product in such a way that it creates a sensation, controversy or brand consciousness among the consumers or customers. The purpose to have increase purchase or to gain popularity in comparison to their competitors, they sometimes use such tactics and techniques, which is highly unethical and immoral for any society. These kinds of stuff used very smartly within the ads that only the conscious mind subconsciously catches the meaning of those glittery images, posters, phrases, tag lines and non-verbal clues. This study elucidates the subliminal advertising their repercussions and impact on consumer’s behaviour in our society with the help of few ads embedded subliminally and the trends of profitability. The methods used to accomplish our research are based on qualitative research along with the research articles, books and feedback from focused groups regarding the topic. The basic objective of this study was that, there is no significant change in the behaviour and attitude observed. These messages capture very short-term life on the viewer’s subconscious mind but in long run people get used to it and hence not only have the diffusion power but also has the high level of acceptance as well that reflects mostly through their social behaviours and attitudes.Keywords: ethical diffusion, subconscious, subliminal advertising, unspoken facts
Procedia PDF Downloads 3271186 Introduction of PMMA-Tag to VHH for Improving Recovery and Immobilization Rate of VHHS
Authors: Bongmun Kang, Kagnari Yamakawa, Yoshihisa Hagihara, Yuji Ito, Michimasa Kishimoto, Yoichi Kumada
Abstract:
The PMMA-tag was genetically fused with the C-terminal region of VHH molecules. This antibody, VHH, is known as a single-chain domain, which is devoid of light chains. The PMMA-tag, which could affect the isoelectric point (pI) changeable with a charge of amino acid in VHHs were closely related to the solubility of VHH molecules during refolding. The genetic fusion of PMMA-tag to C-terminal region of VHHs significantly affects the recovery of their soluble protein during refolding by 50 mM TAPS at pH 8.5. It could be refolded with a recovery of more than 95% by dialysis at pH 8.5. A marked difference in the antigen-binding activities in the adsorption state was significantly high in VHH-PM compared to the wild type of VHH. There are approximately 8-fold differences in the antigen-binding activities in the adsorption state between VHH-PM and VHH.Keywords: VHH, PMMA-tag, isoelectric point, pH, Solubility, refolding, immobilization, ELISA
Procedia PDF Downloads 4171185 A Green Approach towards the Production of CaCO₃ Scaffolds for Bone Tissue Engineering
Authors: Sudhir Kumar Sharma, Abiy D. Woldetsadik, Mazin Magzoub, Ramesh Jagannathan
Abstract:
It is well known that bioactive ceramics exhibit specific biological affinities, especially in the area of tissue re-generation. In this context, we report the development of an eminently scalable, novel, supercritical CO₂ based process for the fabrication of hierarchically porous 'soft' CaCO₃ scaffolds. Porosity at the macro, micro, and nanoscales was obtained through process optimization of the so-called 'coffee-ring effect'. Exposure of these CaCO₃ scaffolds to monocytic THP-1 cells yielded negligible levels of tumor necrosis factor-alpha (TNF-α) thereby confirming the lack of immunogenicity of the scaffolds. ECM protein treatment of the scaffolds showed enhanced adsorption comparable to standard control such as glass. In vitro studies using osteoblast precursor cell line, MC3T3, also demonstrated the cytocompatibility of hierarchical porous CaCO₃ scaffolds.Keywords: supercritical CO2, CaCO3 scaffolds, coffee-ring effect, ECM proteins
Procedia PDF Downloads 3021184 H2/He and H2O/He Separation Experiments with Zeolite Membranes for Nuclear Fusion Applications
Authors: Rodrigo Antunes, Olga Borisevich, David Demange
Abstract:
In future nuclear fusion reactors, tritium self-sufficiency will be ensured by tritium (3H) production via reactions between the fusion neutrons and lithium. To favor tritium breeding, a neutron multiplier must also be used. Both tritium breeder and neutron multiplier will be placed in the so-called Breeding Blanket (BB). For the European Helium-Cooled Pebble Bed (HCPB) BB concept, the tritium production and neutron multiplication will be ensured by neutron bombardment of Li4SiO4 and Be pebbles, respectively. The produced tritium is extracted from the pebbles by purging them with large flows of He (~ 104 Nm3h-1), doped with small amounts of H2 (~ 0.1 vol%) to promote tritium extraction via isotopic exchange (producing HT). Due to the presence of oxygen in the pebbles, production of tritiated water is unavoidable. Therefore, the purging gas downstream of the BB will be composed by Q2/Q2O/He (Q = 1H, 2H, 3H), with Q2/Q2O down to ppm levels, which must be further processed for tritium recovery. A two-stage continuous approach, where zeolite membranes (ZMs) are followed by a catalytic membrane reactor (CMR), has been recently proposed to fulfil this task. The tritium recovery from Q2/Q2O/He is ensured by the CMR, that requires a reduction of the gas flow coming from the BB and a pre-concentration of Q2 and Q2O to be efficient. For this reason, and to keep this stage with reasonable dimensions, ZMs are required upfront to reduce as much as possible the He flows and concentrate the Q2/Q2O species. Therefore, experimental activities have been carried out at the Tritium Laboratory Karlsruhe (TLK) to test the separation performances of different zeolite membranes for H2/H2O/He. First experiments have been performed with binary mixtures of H2/He and H2O/He with commercial MFI-ZSM5 and NaA zeolite-type membranes. Only the MFI-ZSM5 demonstrated selectivity towards H2, with a separation factor around 1.5, and H2 permeances around 0.72 µmolm-2s-1Pa-1, rather independent for feed concentrations in the range 0.1 vol%-10 vol% H2/He. The experiments with H2O/He have demonstrated that the separation factor towards H2O is highly dependent on the feed concentration and temperature. For instance, at 0.2 vol% H2O/He the separation factor with NaA is below 2 and around 1000 at 5 vol% H2O/He, at 30°C. Overall, both membranes demonstrated complementary results at equivalent temperatures. In fact, at low feed concentrations ( ≤ 1 vol% H2O/He) MFI-ZSM5 separates better than NaA, whereas the latter has higher separation factors for higher inlet water content ( ≥ 5 vol% H2O/He). In this contribution, the results obtained with both MFI-ZSM5 and NaA membranes for H2/He and H2O/H2 mixtures at different concentrations and temperatures are compared and discussed.Keywords: nuclear fusion, gas separation, tritium processes, zeolite membranes
Procedia PDF Downloads 2861183 SEC-MALLS Study of Hyaluronic Acid and BSA Thermal Degradation in Powder and in Solution
Authors: Vasile Simulescu, Jakub Mondek, Miloslav Pekař
Abstract:
Hyaluronic acid (HA) is an anionic glycosaminoglycan distributed throughout connective, epithelial and neural tissues. The importance of hyaluronic acid increased in the last decades. It has many applications in medicine and cosmetics. Hyaluronic acid has been used in attempts to treat osteoarthritis of the knee via injecting it into the joint. Bovine serum albumin (also known as BSA) is a protein derived from cows, which has many biochemical applications. The aim of our research work was to compare the thermal degradation of hyaluronic acid and BSA in powder and in solution, by determining changes in molar mass and conformation, by using SEC-MALLS (size exclusion chromatography -multi angle laser light scattering). The aim of our research work was to observe the degradation in powder and in solution of different molar mass hyaluronic acid samples, at different temperatures for certain periods. The degradation of the analyzed samples was mainly observed by modifications in molar mass.Keywords: thermal degradation, hyaluronic acid, BSA, SEC-MALLS
Procedia PDF Downloads 5031182 Differentially Expressed Protein Biomarkers in Early and Advanced Stage Young Triple-Negative Breast Cancer Patients
Authors: Shamim Mushtaq, Moazzam Shahid
Abstract:
Breast cancer (BC) claims the lives of half a million women every year and is the most common cause of death in the developing world. In 2019, it was estimated that BC alone accounts for 15% of all cancer deaths in younger women (aged < 45 years old) with advanced-stage lung metastasis. According to the World Health Organization & International Union against Cancer, in Asia, a high number of cancer-related deaths will be observed in 2020, whereas the burden will be reduced in Western countries due to awareness about the disease, better health facilities and advanced treatments. In the last 15 years, it has been reported that the incidence of BC has increased by 1.1% among Asian compared to the US population from 2003 to 2012. To date, several BC biological subtypes have been reported so far, which are associated with different treatment responses. The heterogeneity and diversity of BC reflected these different subtypes, including Luminal A (23.7% prevalence) and B (38.8% prevalence) that have pathological estrogen receptor (ER+)-positive tumors, the human epidermal growth factor receptor 2 (HER2) (11.2% prevalence) and triple-negative breast cancer (TNBC) (25% prevalence). According to Shaukat Khanum Memorial Cancer Hospital and Research Centre – Pakistan, ten years of data showed that among 636 BC patients, 30.5% had TNBC who were <40 years of age, which is an extremely alarming situation. Therefore, there is a dire need to explore and develop therapeutic targets for the treatment of early TNBC. Since the last decade, unfortunately, there has been little success in understanding the complexity of TNBC and in discovering new biological therapeutic targets. However, conventional chemotherapy is the only choice of treatment for TNBC patients. Many investigators revealed advances in multi-omics (multiple "omes", e.g., genome, proteome, transcriptome, epigenome, and microbiome) which were later identified as actionable targets and increased prevalence in TNBC patients. However, various drugs have been identified so far which are related to a particular diagnostic and prognostic biomarker. For example, Epidermal growth factor receptor ( EGFR or ErbB-1), HER-2/neu (ErbB-2), HER-3 (ErbB-3), and HER-4 (ErbB-4). Protein Transglin-2 (TAGLN 2 ) and Profilins-1 (Pfn-1 ) are the ubiquitously expressed large family of proteins present in all eukaryotes, enabling actin cytoskeletal reorganization. It is known that the oncogenic transformation of cells is accompanied by alteration in the actin cytoskeleton. There are causal connections between altered expression of actin cytoskeletal regulators and cancer progression. Our case-control study identified TAGLN-2 and Pfn-1 proteins in TNBC blood by mass spectrometry. Both TAGLN-2 and Pfn-1 proteins are differentially expressed in early and advanced stages of TNBS patients, which could be potential predictors or therapeutic targets for TNBC.Keywords: TNBC, blood biomarkers, mass spectrometry, qPCR, ELISA
Procedia PDF Downloads 431181 Improvising Grid Interconnection Capabilities through Implementation of Power Electronics
Authors: Ashhar Ahmed Shaikh, Ayush Tandon
Abstract:
The swift reduction of fossil fuels from nature has crucial need for alternative energy sources to cater vital demand. It is essential to boost alternative energy sources to cover the continuously increasing demand for energy while minimizing the negative environmental impacts. Solar energy is one of the reliable sources that can generate energy. Solar energy is freely available in nature and is completely eco-friendly, and they are considered as the most promising power generating sources due to their easy availability and other advantages for the local power generation. This paper is to review the implementation of power electronic devices through Solar Energy Grid Integration System (SEGIS) to increase the efficiency. This paper will also concentrate on the future grid infrastructure and various other applications in order to make the grid smart. Development and implementation of a power electronic devices such as PV inverters and power controllers play an important role in power supply in the modern energy economy. Solar Energy Grid Integration System (SEGIS) opens pathways for promising solutions for new electronic and electrical components such as advanced innovative inverter/controller topologies and their functions, economical energy management systems, innovative energy storage systems with equipped advanced control algorithms, advanced maximum-power-point tracking (MPPT) suited for all PV technologies, protocols and the associated communications. In addition to advanced grid interconnection capabilities and features, the new hardware design results in small size, less maintenance, and higher reliability. The SEGIS systems will make the 'advanced integrated system' and 'smart grid' evolutionary processes to run in a better way. Since the last few years, there was a major development in the field of power electronics which led to more efficient systems and reduction of the cost per Kilo-watt. The inverters became more efficient and had reached efficiencies in excess of 98%, and commercial solar modules have reached almost 21% efficiency.Keywords: solar energy grid integration systems, smart grid, advanced integrated system, power electronics
Procedia PDF Downloads 1821180 Atomic Force Microscopy Studies of DNA Binding Properties of the Archaeal Mini Chromosome Maintenance Complex
Authors: Amna Abdalla Mohammed Khalid, Pietro Parisse, Silvia Onesti, Loredana Casalis
Abstract:
Basic cellular processes as DNA replication are crucial to cell life. Understanding at the molecular level the mechanisms that govern DNA replication in proliferating cells is fundamental to understand disease connected to genomic instabilities, as a genetic disease and cancer. A key step for DNA replication to take place, is unwinding the DNA double helix and this carried out by proteins called helicases. The archaeal MCM (minichromosome maintenance) complex from Methanothermobacter thermautotrophicus have being studied using Atomic Force Microscopy (AFM), imaging in air and liquid (Physiological environment). The accurate analysis of AFM topographic images allowed to understand the static conformations as well the interaction dynamic of MCM and DNA double helix in the present of ATP.Keywords: DNA, protein-DNA interaction, MCM (mini chromosome manteinance) complex, atomic force microscopy (AFM)
Procedia PDF Downloads 3051179 The Relationship between Creative Imagination and Curriculum
Authors: Faride Hashemiannejad, Shima Oloomi
Abstract:
Imagination is one of the important elements of creative thinking which as a skill needs attention by the educational system. Although most students learn reading, writing, and arithmetic skills well, they lack high level thinking skills like creative thinking. Therefore, in the information age and in the beginning of entry to knowledge-based society, the educational system needs to think over its goals and mission, and concentrate on creativity-based curriculum. From among curriculum elements-goals, content, method and evaluation “method” is a major domain whose reform can pave the way for fostering imagination and creativity. The purpose of this study was examining the relationship between creativity development and curriculum. Research questions were: (1) is there a relationship between the cognitive-emotional structure of the classroom and creativity development? (2) Is there a relationship between the environmental-social structure of the classroom and creativity development? (3) Is there a relationship between the thinking structure of the classroom and creativity development? (4) Is there a relationship between the physical structure of the classroom and creativity development? (5) Is there a relationship between the instructional structure of the classroom and creativity development? Method: This research is a applied research and the research method is Correlational research. Participants: The total number of participants in this study included 894 students from High school through 11th grade from seven schools of seven zones in Mashad city. Sampling Plan: Sampling was selected based on Random Multi State. Measurement: The dependent measure in this study was: (a) the Test of Creative Thinking, (b) The researcher-made questionnaire includes five fragments, cognitive, emotional structure, environmental social structure, thinking structure, physical structure, and instructional structure. The Results Show: There was significant relationship between the cognitive-emotional structure of the classroom and student’s creativity development (sig=0.139). There was significant relationship between the environmental-social structure of the classroom and student’s creativity development (sig=0.006). There was significant relationship between the thinking structure of the classroom and student’s creativity development (sig=0.004). There was not significant relationship between the physical structure of the classroom and student’s creativity development (sig=0.215). There was significant relationship between the instructional structure of the classroom and student’s creativity development (sig=0.003). These findings denote if students feel secure, calm and confident, they can experience creative learning. Also the quality of coping with students’ questions, imaginations and risks can influence on their creativity development.Keywords: imagination, creativity, curriculum, bioinformatics, biomedicine
Procedia PDF Downloads 4791178 Adaptation Nature-Based Solutions: CBA of Woodlands for Flood Risk Management in the Aire Catchment, UK
Authors: Olivia R. Rendon
Abstract:
More than half of the world population lives in cities, in the UK, for example, 82% of the population was urban by 2013. Cities concentrate valuable and numerous infrastructure and sectors of the national economies. Cities are particularly vulnerable to climate change which will lead to higher damage costs in the future. There is thus a need to develop and invest in adaptation measures for cities to reduce the impact of flooding and other extreme weather events. Recent flood episodes present a significant and growing challenge to the UK and the estimated cost of urban flood damage is 270 million a year for England and Wales. This study aims to carry out cost-benefit analysis (CBA) of a nature-based approach for flood risk management in cities, focusing on the city of Leeds and the wider Aire catchment as a case study. Leeds was chosen as a case study due to its being one of the most flood vulnerable cities in the UK. In Leeds, over 4,500 properties are currently vulnerable to flooding and approximately £450 million of direct damage is estimated for a potential major flood from the River Aire. Leeds is also the second largest Metropolitan District in England with a projected population of 770,000 for 2014. So far the city council has mainly focused its flood risk management efforts on hard infrastructure solutions for the city centre. However, the wider Leeds district is at significant flood risk which could benefit from greener adaptation measures. This study presents estimates of a nature-based adaptation approach for flood risk management in Leeds. This land use management estimate is based on generating costings utilising primary and secondary data. This research contributes findings on the costs of different adaptation measures to flood risk management in a UK city, including the trade-offs and challenges of utilising nature-based solutions. Results also explore the potential implementation of the adaptation measures in the case study and the challenges of data collection and analysis for adaptation in flood risk management.Keywords: green infrastructure, ecosystem services, woodland, adaptation, flood risk
Procedia PDF Downloads 2841177 Promoting Health and Academic Achievement: Mental Health Promoting Online Education
Authors: Natalie Frandsen
Abstract:
Pursuing post-secondary education is a milestone for many Canadian youths. This transition involves many changes and opportunities for growth. However, this may also be a period where challenges arise. Perhaps not surprisingly, mental health challenges for post-secondary students are common. This poses difficulties for students and instructors. Common mental-health-related symptoms (e.g., low motivation, fatigue, inability to concentrate) can affect academic performance, and instructors may need to provide accommodations for these students without the necessary expertise. ‘Distance education’ has been growing and gaining momentum in Canada for three decades. As a consequence of the COVID-19 pandemic, post-secondary institutions have been required to deliver courses using ‘remote’ methods (i.e., various online delivery modalities). The learning challenges and subsequent academic performance issues experienced by students with mental-health-related disabilities studying online are not well understood. However, we can postulate potential factors drawing from learning theories, the relationship between mental-health-related symptoms and academic performance, and learning design. Identifying barriers and opportunities to academic performance is an essential step in ensuring that students with mental-health-related disabilities are able to achieve their academic goals. Completing post-secondary education provides graduates with more employment opportunities. It is imperative that our post-secondary institutions take a holistic view of learning by providing learning and mental health support while reducing structural barriers. Health-promoting universities and colleges infuse health into their daily operations and academic mandates. Acknowledged in this Charter is the notion that all sectors must take an active role in favour of health, social justice, and equity for all. Drawing from mental health promotion and Universal Design for Learning (UDL) frameworks, relevant adult learning concepts, and critical digital pedagogy, considerations for mental-health-promoting, online learning community development will be summarized. The education sector has the opportunity to create and foster equitable and mental health-promoting learning environments. This is of particular importance during a global pandemic when the mental health of students is being disproportionately impacted.Keywords: academic performance, community, mental health promotion, online learning
Procedia PDF Downloads 1341176 Dys-Regulation of Immune and Inflammatory Response in in vitro Fertilization Implantation Failure Patients under Ovarian Stimulation
Authors: Amruta D. S. Pathare, Indira Hinduja, Kusum Zaveri
Abstract:
Implantation failure (IF) even after the good-quality embryo transfer (ET) in the physiologically normal endometrium is the main obstacle in in vitro fertilization (IVF). Various microarray studies have been performed worldwide to elucidate the genes requisite for endometrial receptivity. These studies have included the population based on different phases of menstrual cycle during natural cycle and stimulated cycle in normal fertile women. Additionally, the literature is also available in recurrent implantation failure patients versus oocyte donors in natural cycle. However, for the first time, we aim to study the genomics of endometrial receptivity in IF patients under controlled ovarian stimulation (COS) during which ET is generally practised in IVF. Endometrial gene expression profiling in IF patients (n=10) and oocyte donors (n=8) were compared during window of implantation under COS by whole genome microarray (using Illumina platform). Enrichment analysis of microarray data was performed to determine dys-regulated biological functions and pathways using Database for Annotation, Visualization and Integrated Discovery, v6.8 (DAVID). The enrichment mapping was performed with the help of Cytoscape software. Microarray results were validated by real-time PCR. Localization of genes related to immune response (Progestagen-Associated Endometrial Protein (PAEP), Leukaemia Inhibitory Factor (LIF), Interleukin-6 Signal Transducer (IL6ST) was detected by immunohistochemistry. The study revealed 418 genes downregulated and 519 genes upregulated in IF patients compared to healthy fertile controls. The gene ontology, pathway analysis and enrichment mapping revealed significant downregulation in activation and regulation of immune and inflammation response in IF patients under COS. The lower expression of Progestagen Associated Endometrial Protein (PAEP), Leukemia Inhibitory Factor (LIF) and Interleukin 6 Signal Transducer (IL6ST) in cases compared to controls by real time and immunohistochemistry suggests the functional importance of these genes. The study was proved useful to uncover the probable reason of implantation failure being imbalance of immune and inflammatory regulation in our group of subjects. Based on the present study findings, a panel of significant dysregulated genes related to immune and inflammatory pathways needs to be further substantiated in larger cohort in natural as well as stimulated cycle. Upon which these genes could be screened in IF patients during window of implantation (WOI) before going for embryo transfer or any other immunological treatment. This would help to estimate the regulation of specific immune response during WOI in a patient. The appropriate treatment of either activation of immune response or suppression of immune response can be then attempted in IF patients to enhance the receptivity of endometrium.Keywords: endometrial receptivity, immune and inflammatory response, gene expression microarray, window of implantation
Procedia PDF Downloads 1531175 Mechanisms of O-1602 Induced Endothelium-Independent Vasorelaxation of Rat Small Mesenteric Artery
Authors: Yousuf Al Suleimani, Ahmed Al Mahruqi
Abstract:
A typical cannabinoid O-1602 induces vasorelaxation and activates the orphan G protein-coupled receptor GPR55 in human endothelial cells. The aim of this study is to characterize the mechanisms of endothelium-independent relaxation of O-1602 in the rat small mesenteric artery using wire myograph. In endothelium-denuded vessels, O-1602 partially produced concentration-dependent vasorelaxation. In vessels depleted of intracellular Ca2+ (by EGTA and methoxamine), CaCl2 produced concentration-dependent contraction. Preincubation with O-1602 (at 10 µM and 30 µM) abolished the contractile responses (P<0.01). The putative antagonist at novel “endothelial anandamide receptor” O-1918 (10 µM) significantly reversed the inhibitory effect of O-1602 on CaCl2-induced vasoconstriction. It is likely that the mechanism of endothelium-independent vasorelaxation to O-1602 is mediated by interfering with Ca2+ entry via an O-1918-sensitive pathway.Keywords: O-1602, endothelium, vasorelaxation, calcium
Procedia PDF Downloads 3571174 Association of Zinc with New Generation Cardiovascular Risk Markers in Childhood Obesity
Authors: Mustafa M. Donma, Orkide Donma
Abstract:
Zinc is a vital element required for growth and development. This fact makes zinc important, particularly for children. It maintains normal cellular structure and functions. This essential element appears to have protective effects against coronary artery disease and cardiomyopathy. Higher serum zinc levels are associated with lower risk of cardiovascular diseases (CVDs). There is a significant association between low serum zinc levels and heart failure. Zinc may be a potential biomarker of cardiovascular health. High sensitive cardiac troponin T (hs-cTnT) and cardiac myosin binding protein C (cMyBP-C) are new generation markers used for prediagnosis, diagnosis, and prognosis of CVDs. The aim of this study is to determine zinc as well as new generation cardiac markers profiles in children with normal body mass index (N-BMI), obese (OB), morbid obese (MO) children, and children with metabolic syndrome (MetS) findings. The association among them will also be investigated. Four study groups were constituted. The study protocol was approved by the institutional Ethics Committee of Tekirdag Namik Kemal University. Parents of the participants filled informed consent forms to participate in the study. Group 1 is composed of 44 children with N-BMI. Group 2 and Group 3 comprised 43 OB and 45 MO children, respectively. Forty-five MO children with MetS findings were included in Group 4. World Health Organization age- and sex-adjusted BMI percentile tables were used to constitute groups. These values were 15-85, 95-99, and above 99 for N-BMI, OB, and MO, respectively. Criteria for MetS findings were determined. Routine biochemical analyses, including zinc, were performed. High sensitive-cTnT and cMyBP-C concentrations were measured by kits based on enzyme-linked immunosorbent assay principle. Appropriate statistical tests within the scope of SPSS were used for the evaluation of the study data. p<0.05 was accepted as statistically significant. Four groups were matched for age and gender. Decreased zinc concentrations were measured in Groups 2, 3, and 4 compared to Group 1. Groups did not differ from one another in terms of hs-cTnT. There were statistically significant differences between cMyBP-C levels of MetS group and N-BMI as well as OB groups. There was an increasing trend going from N-BMI group to MetS group. There were statistically significant negative correlations between zinc and hs-cTnT as well as cMyBP-C concentrations in MetS group. In conclusion, inverse correlations detected between zinc and new generation cardiac markers (hs-TnT and cMyBP-C) have pointed out that decreased levels of this physiologically essential trace element accompany increased levels of hs-cTnT as well as cMyBP-C in children with MetS. This finding emphasizes that both zinc and these new generation cardiac markers may be evaluated as biomarkers of cardiovascular health during severe childhood obesity precipitated with MetS findings and also suggested as the messengers of the future risk in the adulthood periods of children with MetS.Keywords: cardiac myosin binding protein-C, cardiovascular diseases, children, high sensitive cardiac troponin T, obesity
Procedia PDF Downloads 1071173 Effect of Dust Rejected by Iron and Steel Complex on Roots of Bean Phaseolus vulgaris
Authors: Labiba Zerari Bourafa, Djebar Mohamed Reda, Berrebah Houria, Khadri Sihem, Chiheb Linda
Abstract:
The study of the effect of metal dust (pollutants) was performed on higher plant white beans Phaseolus vulgaris; the experience took place in cellular toxicology laboratory (in vitro culture). The seeds of the bean Phaseolus vulgaris are cultured in a metal contaminated dust medium (a single treatment by different increasing doses), at a rate of 10 seeds per box, for 10 days. The measurement of morpho-metric parameters is performed during the first 96 hours that follow the germination; while the dosage of the proline, the protein content and histological sections are formed on the tenth day (240 h). All morpho-metric and biochemical parameters measured were highly disturbed by metal dust; histological sections confirm this disurbance.Keywords: conductive fabrics, metal dust, osmoticums, roots, Phaseolus vulgaris
Procedia PDF Downloads 3741172 Activation of TNF-α from Human Endothelial Cells by Exposure of the Mitochondrial Stress Protein (Hsp60) Secreted from THP-1 Monocytes to High Glucose
Authors: Ryan D. Martinus
Abstract:
Inflammation of the endothelium is an important process leading to diabetic atherosclerosis. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Using In-vitro cultured Human cells and Hsp60 specific ELISA assays, we show that Hsp60 is not only induced in Human monocyte cells under hyperglycaemic conditions but that the Hsp60 is also secreted from these cells. Furthermore, we also demonstrate that the Hsp60 secreted from these monocyte cells is also able to activate Toll-like receptor-4 (TLR4) from Human endothelial cells. This suggests that a potential link may exist between the hyperglycaemia-induced expression of Hsp60 in monocyte cells and vascular inflammation. Circulating levels of Hsp60 due to mitochondrial stress in diabetes patients could, therefore, be an important modulator of inflammation in endothelial cells and thus contribute to the increased incidences of atherosclerosis in diabetes mellitus.Keywords: mitochondria, Hsp60, inflammation, diabetes mellitus
Procedia PDF Downloads 1791171 Improved Signal-To-Noise Ratio by the 3D-Functionalization of Fully Zwitterionic Surface Coatings
Authors: Esther Van Andel, Stefanie C. Lange, Maarten M. J. Smulders, Han Zuilhof
Abstract:
False outcomes of diagnostic tests are a major concern in medical health care. To improve the reliability of surface-based diagnostic tests, it is of crucial importance to diminish background signals that arise from the non-specific binding of biomolecules, a process called fouling. The aim is to create surfaces that repel all biomolecules except the molecule of interest. This can be achieved by incorporating antifouling protein repellent coatings in between the sensor surface and it’s recognition elements (e.g. antibodies, sugars, aptamers). Zwitterionic polymer brushes are considered excellent antifouling materials, however, to be able to bind the molecule of interest, the polymer brushes have to be functionalized and so far this was only achieved at the expense of either antifouling or binding capacity. To overcome this limitation, we combined both features into one single monomer: a zwitterionic sulfobetaine, ensuring antifouling capabilities, equipped with a clickable azide moiety which allows for further functionalization. By copolymerizing this monomer together with a standard sulfobetaine, the number of azides (and with that the number of recognition elements) can be tuned depending on the application. First, the clickable azido-monomer was synthesized and characterized, followed by copolymerizing this monomer to yield functionalizable antifouling brushes. The brushes were fully characterized using surface characterization techniques like XPS, contact angle measurements, G-ATR-FTIR and XRR. As a proof of principle, the brushes were subsequently functionalized with biotin via strain-promoted alkyne azide click reactions, which yielded a fully zwitterionic biotin-containing 3D-functionalized coating. The sensing capacity was evaluated by reflectometry using avidin and fibrinogen containing protein solutions. The surfaces showed excellent antifouling properties as illustrated by the complete absence of non-specific fibrinogen binding, while at the same time clear responses were seen for the specific binding of avidin. A great increase in signal-to-noise ratio was observed, even when the amount of functional groups was lowered to 1%, compared to traditional modification of sulfobetaine brushes that rely on a 2D-approach in which only the top-layer can be functionalized. This study was performed on stoichiometric silicon nitride surfaces for future microring resonator based assays, however, this methodology can be transferred to other biosensor platforms which are currently being investigated. The approach presented herein enables a highly efficient strategy for selective binding with retained antifouling properties for improved signal-to-noise ratios in binding assays. The number of recognition units can be adjusted to a specific need, e.g. depending on the size of the analyte to be bound, widening the scope of these functionalizable surface coatings.Keywords: antifouling, signal-to-noise ratio, surface functionalization, zwitterionic polymer brushes
Procedia PDF Downloads 3051170 Governance Framework for an Emerging Trust Ecosystem with a Blockchain-Based Supply Chain
Authors: Ismael Ávila, José Reynaldo F. Filho, Vasco Varanda Picchi
Abstract:
The ever-growing consumer awareness of food provenance in Brazil is driving the creation of a trusted ecosystem around the animal protein supply chain. The traceability and accountability requirements of such an ecosystem demand a blockchain layer to strengthen the weak links in that chain. For that, direct involvement of the companies in the blockchain transactions, including as validator nodes of the network, implies formalizing a partnership with the consortium behind the ecosystem. Yet, their compliance standards usually require that a formal governance structure is in place before they agree with any membership terms. In light of such a strategic role of blockchain governance, the paper discusses a framework for tailoring a governance model for a blockchain-based solution aimed at the meat supply chain and evaluates principles and attributes in terms of their relevance to the development of a robust trust ecosystem.Keywords: blockchain, governance, trust ecosystem, supply chain, traceability
Procedia PDF Downloads 1171169 The Anti-Inflammatory Effects of Nanodiamond Particles and Lipoic Acid on Rats' Cardiovascular System
Authors: Beata Skibska, Andrzej Stanczak, Agnieszka Skibska
Abstract:
Nanodiamond (ND) is a carbon nanomaterial that has high biocompatibility, and it has a very positive effect on a number of biochemical processes. NDs have great potential in treating multiple inflammation-associated diseases. The purpose of this study was to investigate the anti-inflammatory effect of nanodiamonds and lipoic acid (LA) (as antioxidants) on rats' cardiovascular systems after lipopolysaccharide (LPS) administration. Animal experiments enabled the determination of how nanodiamonds act when applied independently or in combination with lipoic acid. The effect of NDs and LA on C-reactive protein (CRP) levels and heart edema was evaluated. NDs and LA administered after LPS administration attenuated heart edema and significantly decreased the CRP level. The results suggest that NDs and LA play an important role in LPS-induced inflammation in the heart. NDs find new applications in modern biomedical science and biotechnologies.Keywords: nanodiamonds, lipoic acid, inflammation, cardiovascular system
Procedia PDF Downloads 841168 Investigating the Role of Circular RNA GATAD2A on H1N1 Replication
Authors: Tianqi Yu, Yingnan Ding, Yina Zhang, Yulan Liu, Yahui Li, Jing Lei, Jiyong Zhou, Suquan Song, Boli Hu
Abstract:
Circular RNAs (circRNAs) play critical roles in various diseases. However, whether and how circular RNA regulates influenza A virus (IAV) infection is unknown. Here, we studied the role of circular RNA GATA Zinc Finger Domain Containing 2A (circ-GATAD2A) in the replication of IAV H1N1 in A549 cells. Circ-GATAD2A was formed upon H1N1 infection. Knockdown of circ-GATAD2A in A549 cells enhanced autophagy and inhibited H1N1 replication. By contrast, overexpression of circ-GATAD2A impaired autophagy and promoted H1N1 replication. Similarly, knockout of vacuolar protein sorting 34 (VPS34) blocked autophagy and increased H1N1 replication. However, the expression of circ-GATAD2A could not further enhance H1N1 replication in VPS34 knockout cells. Collectively, these data indicated that circ-GATAD2A promotes the replication of H1N1 by inhibiting autophagy.Keywords: autophagy, circ-GATAD2A, H1N1, replication
Procedia PDF Downloads 1531167 Hepatoprotective Effect of Mycophenolate Mofetil against Tacrolimus Exposure in Rat
Authors: Ferjani Hanen, El Arem Amira, Boussema Ayed Imen, Bacha Hassen
Abstract:
Tacrolimus (TAC), a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant recipient, but its use associated-hepatotoxicity. Mycophenolate mofetil (MMF), an anti-metabolite, is a potent immunosuppressive drug. MMF is not hepatotoxic and is the most common adjunctive immunosuppressant for TAC. The effects of TAC and MMF combination in the liver is still not well understood. This work aimed to investigate their combined effect against in liver in rats Wistar after 24 h. The oral median lethal doses (LD50) of TAC and MMF alone were evaluated in rats are 240 mg/kg and 500 mg/kg respectively. Oral administration of the MMF at 50 mg/kg to male Wistar intoxicated with TAC at 60 mg/kg, demonstrated a significant protective effect by lowering the levels of hepatic markers enzymes (AST, ALT) in the serum rat. MMF attenuated oxidative stress by restoring the activities of SOD, CAT and by reducing the malondialdehyde (MDA) and protein carbonyl levels liver. This study provided evidence that MMF protects rat liver from TAC-induced injury and suggests a most combination use for organ transplantation.Keywords: tacrolimus, mycophenolate mofetil, combination, liver, rat
Procedia PDF Downloads 3341166 Revolutionizing Legal Drafting: Leveraging Artificial Intelligence for Efficient Legal Work
Authors: Shreya Poddar
Abstract:
Legal drafting and revising are recognized as highly demanding tasks for legal professionals. This paper introduces an approach to automate and refine these processes through the use of advanced Artificial Intelligence (AI). The method employs Large Language Models (LLMs), with a specific focus on 'Chain of Thoughts' (CoT) and knowledge injection via prompt engineering. This approach differs from conventional methods that depend on comprehensive training or fine-tuning of models with extensive legal knowledge bases, which are often expensive and time-consuming. The proposed method incorporates knowledge injection directly into prompts, thereby enabling the AI to generate more accurate and contextually appropriate legal texts. This approach substantially decreases the necessity for thorough model training while preserving high accuracy and relevance in drafting. Additionally, the concept of guardrails is introduced. These are predefined parameters or rules established within the AI system to ensure that the generated content adheres to legal standards and ethical guidelines. The practical implications of this method for legal work are considerable. It has the potential to markedly lessen the time lawyers allocate to document drafting and revision, freeing them to concentrate on more intricate and strategic facets of legal work. Furthermore, this method makes high-quality legal drafting more accessible, possibly reducing costs and expanding the availability of legal services. This paper will elucidate the methodology, providing specific examples and case studies to demonstrate the effectiveness of 'Chain of Thoughts' and knowledge injection in legal drafting. The potential challenges and limitations of this approach will also be discussed, along with future prospects and enhancements that could further advance legal work. The impact of this research on the legal industry is substantial. The adoption of AI-driven methods by legal professionals can lead to enhanced efficiency, precision, and consistency in legal drafting, thereby altering the landscape of legal work. This research adds to the expanding field of AI in law, introducing a method that could significantly alter the nature of legal drafting and practice.Keywords: AI-driven legal drafting, legal automation, futureoflegalwork, largelanguagemodels
Procedia PDF Downloads 611165 Interruption Overload in an Office Environment: Hungarian Survey Focusing on the Factors that Affect Job Satisfaction and Work Efficiency
Authors: Fruzsina Pataki-Bittó, Edit Németh
Abstract:
On the one hand, new technologies and communication tools improve employee productivity and accelerate information and knowledge transfer, while on the other hand, information overload and continuous interruptions make it even harder to concentrate at work. It is a great challenge for companies to find the right balance, while there is also an ongoing demand to recruit and retain the talented employees who are able to adopt the modern work style and effectively use modern communication tools. For this reason, this research does not focus on the objective measures of office interruptions, but aims to find those disruption factors which influence the comfort and job satisfaction of employees, and the way how they feel generally at work. The focus of this research is on how employees feel about the different types of interruptions, which are those they themselves identify as hindering factors, and those they feel as stress factors. By identifying and then reducing these destructive factors, job satisfaction can reach a higher level and employee turnover can be reduced. During the research, we collected information from depth interviews and questionnaires asking about work environment, communication channels used in the workplace, individual communication preferences, factors considered as disruptions, and individual steps taken to avoid interruptions. The questionnaire was completed by 141 office workers from several types of workplaces based in Hungary. Even though 66 respondents are working at Hungarian offices of multinational companies, the research is about the characteristics of the Hungarian labor force. The most important result of the research shows that while more than one third of the respondents consider office noise as a disturbing factor, personal inquiries are welcome and considered useful, even if in such cases the work environment will not be convenient to solve tasks requiring concentration. Analyzing the sizes of the offices, in an open-space environment, the rate of those who consider office noise as a disturbing factor is surprisingly lower than in smaller office rooms. Opinions are more diverse regarding information communication technologies. In addition to the interruption factors affecting the employees' job satisfaction, the research also focuses on the role of the offices in the 21st century.Keywords: information overload, interruption, job satisfaction, office environment, work efficiency
Procedia PDF Downloads 2261164 In silico Analysis of Isoniazid Resistance in Mycobacterium tuberculosis
Authors: A. Nusrath Unissa, Sameer Hassan, Luke Elizabeth Hanna
Abstract:
Altered drug binding may be an important factor in isoniazid (INH) resistance, rather than major changes in the enzyme’s activity as a catalase or peroxidase (KatG). The identification of structural or functional defects in the mutant KatGs responsible for INH resistance remains as an area to be explored. In this connection, the differences in the binding affinity between wild-type (WT) and mutants of KatG were investigated, through the generation of three mutants of KatG, Ser315Thr [S315T], Ser315Asn [S315N], Ser315Arg [S315R] and a WT [S315]) with the help of software-MODELLER. The mutants were docked with INH using the software-GOLD. The affinity is lower for WT than mutant, suggesting the tight binding of INH with the mutant protein compared to WT type. These models provide the in silico evidence for the binding interaction of KatG with INH and implicate the basis for rationalization of INH resistance in naturally occurring KatG mutant strains of Mycobacterium tuberculosis.Keywords: Mycobacterium tuberculosis, KatG, INH resistance, mutants, modelling, docking
Procedia PDF Downloads 316