Search results for: myelin basic protein
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5314

Search results for: myelin basic protein

4414 The Role of Piceatannol in Counteracting Glyceraldehyde-3-Phosphate Dehydrogenase Aggregation and Nuclear Translocation

Authors: Joanna Gerszon, Aleksandra Rodacka

Abstract:

In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).

Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation

Procedia PDF Downloads 167
4413 The Impact of Missense Mutation in Phosphatidylinositol Glycan Class A Associated to Paroxysmal Nocturnal Hemoglobinuria and Multiple Congenital Anomalies-Hypotonia-Seizures Syndrome 2: A Computational Study

Authors: Ashish Kumar Agrahari, Amit Kumar

Abstract:

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal blood disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The disease is caused by the deficiency of two glycosylphosphatidylinositols (GPI)-anchored proteins (CD55 and CD59) in the hemopoietic stem cells. The deficiency of GPI-anchored proteins has been associated with the somatic mutations in phosphatidylinositol glycan class A (PIGA). However, the mutations that do not cause PNH is associated with the multiple congenital anomalies-hypotonia-seizures syndrome 2 (MCAHS2). To best of our knowledge, no computational study has been performed to explore the atomistic level impact of PIGA mutations on the structure and dynamics of the protein. In the current work, we are mainly interested to get insights into the molecular mechanism of PIGA mutations. In the initial step, we screened the most pathogenic mutations from the pool of publicly available mutations. Further, to get a better understanding, pathogenic mutations were mapped to the modeled structure and subjected to 50ns molecular dynamics simulation. Our computational study suggests that four mutations are highly vulnerable to altering the structural conformation and stability of the PIGA protein, which illustrates its association with PNH and MCAHS2 phenotype.

Keywords: homology modeling, molecular dynamics simulation, missense mutations PNH, MCAHS2, PIGA

Procedia PDF Downloads 145
4412 Evaluating the Understanding of the University Students (Basic Sciences and Engineering) about the Numerical Representation of the Average Rate of Change

Authors: Saeid Haghjoo, Ebrahim Reyhani, Fahimeh Kolahdouz

Abstract:

The present study aimed to evaluate the understanding of the students in Tehran universities (Iran) about the numerical representation of the average rate of change based on the Structure of Observed Learning Outcomes (SOLO). In the present descriptive-survey research, the statistical population included undergraduate students (basic sciences and engineering) in the universities of Tehran. The samples were 604 students selected by random multi-stage clustering. The measurement tool was a task whose face and content validity was confirmed by math and mathematics education professors. Using Cronbach's Alpha criterion, the reliability coefficient of the task was obtained 0.95, which verified its reliability. The collected data were analyzed by descriptive statistics and inferential statistics (chi-squared and independent t-tests) under SPSS-24 software. According to the SOLO model in the prestructural, unistructural, and multistructural levels, basic science students had a higher percentage of understanding than that of engineering students, although the outcome was inverse at the relational level. However, there was no significant difference in the average understanding of both groups. The results indicated that students failed to have a proper understanding of the numerical representation of the average rate of change, in addition to missconceptions when using physics formulas in solving the problem. In addition, multiple solutions were derived along with their dominant methods during the qualitative analysis. The current research proposed to focus on the context problems with approximate calculations and numerical representation, using software and connection common relations between math and physics in the teaching process of teachers and professors.

Keywords: average rate of change, context problems, derivative, numerical representation, SOLO taxonomy

Procedia PDF Downloads 92
4411 Novel p22-Monoclonal Antibody Based Blocking ELISA for the Detection of African Swine Fever Virus Antibodies in Serum

Authors: Ghebremedhin Tsegay, Weldu Tesfagaber, Yuanmao Zhu, Xijun He, Wan Wang, Zhenjiang Zhang, Encheng Sun, Jinya Zhang, Yuntao Guan, Fang Li, Renqiang Liu, Zhigao Bu, Dongming Zhao*

Abstract:

African swine fever (ASF) is a highly infectious viral disease of pigs, resulting in significant economic loss worldwide. As there is no approved vaccines and treatments, the control of ASF entirely depends on early diagnosis and culling of infected pigs. Thus, highly specific and sensitive diagnostic assays are required for accurate and early diagnosis of ASF virus (ASFV). Currently, only a few recombinant proteins have been tested and validated for use as reagents in ASF diagnostic assays. The most promising ones for ASFV antibody detection were p72, p30, p54, and pp62. So far, three ELISA kits based on these recombinant proteins have been commercialized. Due to the complex nature of the virus and variety forms of the disease, robust serodiagnostic assays are still required. ASFV p22 protein, encoded by KP177R gene, is located in the inner membrane of viral particle and appeared transiently in the plasma membrane early after virus infection. The p22 protein interacts with numerous cellular proteins, involved in processes of phagocytosis and endocytosis through different cellular pathways. However, p22 does not seem to be involved in virus replication or swine pathogenicity. In this study, E.coli expressed recombinant p22 protein was used to generate a monoclonal antibody (mAb), and its potential use for the development of blocking ELISA (bELISA) was evaluated. A total of 806 pig serum samples were tested to evaluate the bELISA. Acording the ROC (Reciever operating chracteristic) analysis, 100% sensitivity and 98.10% of specificity was recorded when the PI cut-off value was set at 47%. The novel assay was able to detect the antibodies as early as 9 days post infection. Finaly, a highly sensitive, specific and rapid novel p22-mAb based bELISA assay was developed, and optimized for detection of antibodies against genotype I and II ASFVs. It is a promising candidate for an early and acurate detection of the antibodies and is highly expected to have a valuable role in the containment and prevention of ASF.

Keywords: ASFV, blocking ELISA, diagnosis, monoclonal antibodies, sensitivity, specificity

Procedia PDF Downloads 77
4410 A Simple Approach for the Analysis of First Vibration Mode of Layered Soil Profiles

Authors: Haizhong Zhang, Yan-Gang Zhao

Abstract:

Fundamental period, mode shape, and participation factor are important basic information for the understanding of earthquake response of ground. In this study, a simple approach is presented to calculate these basic information of layered soil profiles. To develop this method, closed form equations are derived for analysis of free vibration of layered soil profiles firstly, based on equilibrium between inertia and elastic forces. Then, by further associating with the Madera procedure developed for estimation of fundamental period, a simple method that can directly determine the fundamental period, mode shape and participation factor is proposed. The proposed approach can be conveniently implemented in simple spreadsheets and easily used by practicing engineers. In addition, the accuracy of the proposed approach is investigated by analyzing first vibration mode of 67 representative layered soil profiles, it is found that results by the proposed method agree very well with accurate results.

Keywords: layered soil profile, natural vibration, fundamental period, fundamental mode shape

Procedia PDF Downloads 326
4409 Strategies and Problems of Teachers in Using Mother Tongue-Based Multilingual Education

Authors: Ezayra Dubria, Leonora Yambao

Abstract:

Mother Tongue–Based Multilingual Education (MTB-MLE) is a salient part of the recent reform in the country’s Education system which is the implementation of the K to 12 Basic Education Program. Its importance is highlighted by the passing of Republic Act 10523, otherwise known as the ‘Enhanced Basic Education Act of 2013’. However, teachers, especially new teachers encounter problems in using mother tongue as medium of instruction. Fortunately, teachers are able to create strategies which address these problems. Specifically, this paper gathered the viewpoints of teachers in using mother tongue and analyzed the different problems and strategies used. The problems encountered by teachers are lack of instructional materials written in mother tongue, especially books, lack of vocabulary, lack of teacher training, and influences of social media to learners. The strategies which address these problems are translation of literary pieces and other instructional materials, vocabulary enrichment through the use of word-of-the-day and picture-word association, remedial class, storytelling, differentiated instruction, explicit teaching, individual and group activities, and utilization of multilingual teaching.

Keywords: mother tongue-based instruction, multilingualism, problems, strategies

Procedia PDF Downloads 294
4408 Nutritional Management of Polycystic Ovary Syndrome Using a Mediterranean Diet

Authors: Mohamed Radwan

Abstract:

Introduction: Polycystic ovary syndrome is becoming very common among girls from ages 14 to 21 years old, alongside women in their childbearing period. A combination of menstrual irregularities, overweight or obesity, insulin resistance (type 2 diabetes), and symptoms of virilization are characteristics of these cases. Background: A multidisciplinary team should be involved in managing these cases and may consist of A gynecologist, endocrinologist, nutritionist, and psychologist. The role of nutritionists is crucial in these cases in weight reduction and nutritional management. It is mandatory to present some questions that may help in expanding further our understanding of the nutritional management of this syndrome, such as it is not an easy process to reduce the weight of PCO patients (2) we need to know what suitable nutritional plans for these cases are. Methodology: It is not successful to use one diet plan for all patients or a specific plan, but we need to give tailored plans for each patient. We will summarize the medical, nutritional therapy and weight management in polycystic ovary patients and highlight the best eating plan and dietary composition in the treatment of these women. We will also discuss the role of dieticians in treating polycystic ovary cases and overcoming the challenges these women face. Conclusion: All diet plans would decrease the weight of Polycystic ovary cases as low calory diet, low glycemic index diet, high protein diet, as well as Dash diet, but the most suitable diet plan to improve hormones and lead to spontaneous pregnancy is the Mediterranean diet.

Keywords: obesity, PCO mediteranian diet, dash diet, high protein diet

Procedia PDF Downloads 76
4407 COVID-19 Vaccine Hesitancy: The Role of Existential Concerns in Individual’s Decisions Regarding the Vaccine Uptake

Authors: Vittoria Franchina, Laura Salerno, Rubinia Celeste Bonfanti, Gianluca Lo Coco

Abstract:

This study examines the relationships between existential concerns (ECs), basic psychological needs (BPNs), vaccine hesitancy (VH), and the mediating role of negative attitudes toward COVID-19 vaccines. A cross-sectional survey was carried out on a sample of two-hundred eighty-seven adults (Mage = 36.04 (12.07); 59.9% females). Participants were recruited online through clickworker and filled in measures on existential concerns, basic psychological needs, attitudes toward COVID-19 vaccines, and vaccine hesitancy for Pfizer-BioNTech and Astrazeneca vaccines separately. Structural equation modelling showed that existential concerns were related to Pfizer-BioNTech and Astrazeneca vaccine hesitancy both directly and indirectly through negative attitudes toward possible side effects of COVID-19 vaccines. The present study has identified several predictive factors relating to the intention to uptake vaccination to protect against COVID-19 in Italy. Specifically, these findings suggest a causal link between existential concerns, attitudes, and vaccine hesitancy.

Keywords: COVID-19, existential concerns, Pfizer-BioNTech and Astrazeneca vaccines, vaccine hesitancy

Procedia PDF Downloads 100
4406 Expression of Metallothionein Gen and Protein on Hepatopancreas, Gill and Muscle of Perna viridis Caused by Biotoxicity Hg, Pb and Cd

Authors: Yulia Irnidayanti , J. J. Josua, A. Sugianto

Abstract:

Jakarta Bay with 13 rivers that flow into, the environment has deteriorated and is the most polluted bays in Asia. The entry of waste into the waters of the Bay of Jakarta has caused pollution. Heavy metal contamination has led to pollution levels and may cause toxicity to organisms that live in the sea, down to the cellular level and may affect the ecological balance. Various ways have been conducted to measure the impact of environmental degradation, such as by measuring the levels of contaminants in the environment, including measuring the accumulation of toxic compounds in the tissues of organisms. Biological responses or biomarkers known as a sensitive indicator but need relevant predictions. In heavy metal pollution monitoring, analysis of aquatic biota is very important from the analysis of the water itself. The content of metals in aquatic biota will usually always be increased from time to time due to the nature of metal bioaccumulation, so the aquatic biota is best used as an indicator of metal pollution in aquatic environments. The results of the content analysis results of sea water in coastal estuaries Angke, Kaliadem and Panimbang detected heavy metals cadmium, mercury, lead, but did not find zinc metal. Based on the results of protein electrophoresis methallotionein found heavy metals in the tissues hepatopancreas, gills and muscles, and also the mRNA expression of has detected.

Keywords: gills, heavy metal, hepatopancreas, metallothionein, muscle

Procedia PDF Downloads 389
4405 The Problem of Access to Water, Sanitation and Hygiene in Small Island Towns: The Case of Foundiougne in Senegal

Authors: El Hadji Mamadou Sonko, Ndiogou Sankhare, Maïmouna Lo, Jean Birane Gning, Cheikh Diop

Abstract:

In Senegal, access to water, hygiene, and sanitation in small island towns is a particular problem, which is still poorly understood by the public authorities and development aid actors. The main objective of this study carried out in the Municipality of Foundiougne is to contribute to the knowledge of the problems related to the supply of drinking water, access to sanitation, and hygiene in small island towns in Senegal. The methodology adopted consisted of a literature review and quantitative surveys of a sample of 100 households in the Municipality. Semi-structured interviews using interview guides and informal interviews were also conducted with mechanical and manual emptiers, municipal authorities, public toilet managers, and neighbourhood leaders. Direct observation with photography was also used. The results show that, with regard to access to drinking water, 35% of households have unimproved water services, 46% have a limited level of service, and 19% have a basic level of service. Regarding sanitation, 77% of households are considered to have access to basic sanitation services, compared to 23% with limited sanitation services. However, these figures hide the dysfunctions of the sanitation system. Indeed, manual emptying is practiced exclusively by 4% of households, while 17% of households combine it with mechanical emptying. In addition, domestic wastewater is mainly evacuated outside the sanitation facilities, and all the sludge extracted from the pits is discharged directly into the environment without treatment. As a matter of fact, the surveys showed that 52% of households do not have access to a basic level of hygiene-related to handwashing when leaving the toilet. These results show that there is real work to be done at the level of small urban centres if we want to achieve MDG 6.

Keywords: Foundiougne, Senegal, small island, small town, water-sanitation, hygiene

Procedia PDF Downloads 96
4404 Visualizing Matrix Metalloproteinase-2 Activity Using Extracellular Matrix-Immobilized Fluorescence Resonance Energy Transfer Bioprobe in Cancer Cells

Authors: Hawon Lee, Young-Pil Kim

Abstract:

Visualizing matrix metalloproteinases (MMPs) activity is necessary for understanding cancer metastasis because they are implicated in cell migration and invasion by degrading the extracellular matrix (ECM). While much effort has been made to sense the MMP activity, but extracellularly long-term monitoring of MMP activity still remains challenging. Here, we report a collagen-bound fluorescent bioprobe for the detection of MMP-2 activity in the extracellular environment. This bioprobe consists of ECM-immobilized part (including collagen-bound protein) and MMP-sensing part (including peptide substrate linked with fluorescence resonance energy transfer (FRET) coupler between donor green fluorescent protein (GFP) and acceptor TAMRA dye), which was constructed through intein-mediated self-splicing conjugation. Upon being immobilized on the collagen-coated surface, this bioprobe enabled efficient long-lasting observation of MMP-2 activity in the cultured cells without affecting cell growth and viability. As a result, the FRET ratio (acceptor/donor) decreased as the MMP2 activity increased in cultured cancer cells. Furthermore, unlike wild-type MMP-2, mutated MMP-2 expression (Y580A in the hemopexin region) gave rise to lowering the secretion of MMP-2 in HeLa. Conclusively, our method is anticipated to find applications for tracing and visualizing enzyme activity.

Keywords: collagen, ECM, FRET, MMP

Procedia PDF Downloads 202
4403 Toward Understanding the Glucocorticoid Receptor Network in Cancer

Authors: Swati Srivastava, Mattia Lauriola, Yuval Gilad, Adi Kimchi, Yosef Yarden

Abstract:

The glucocorticoid receptor (GR) has been proposed to play important, but incompletely understood roles in cancer. Glucocorticoids (GCs) are widely used as co-medication of various carcinomas, due to their ability to reduce the toxicity of chemotherapy. Furthermore, GR antagonism has proven to be a strategy to treat triple negative breast cancer and castration-resistant prostate cancer. These observations suggest differential GR involvement in cancer subtypes. The goal of our study has been to elaborate the current understanding of GR signaling in tumor progression and metastasis. Our study involves two cellular models, non-tumorigenic breast epithelial cells (MCF10A) and Ewing sarcoma cells (CHLA9). In our breast cell model, the results indicated that the GR agonist dexamethasone inhibits EGF-induced mammary cell migration, and this effect was blocked when cells were stimulated with a GR antagonist, namely RU486. Microarray analysis for gene expression revealed that the mechanism underlying inhibition involves dexamenthasone-mediated repression of well-known activators of EGFR signaling, alongside with enhancement of several EGFR’s negative feedback loops. Because GR mainly acts primarily through composite response elements (GREs), or via a tethering mechanism, our next aim has been to find the transcription factors (TFs) which can interact with GR in MCF10A cells.The TF-binding motif overrepresented at the promoter of dexamethasone-regulated genes was predicted by using bioinformatics. To validate the prediction, we performed high-throughput Protein Complementation Assays (PCA). For this, we utilized the Gaussia Luciferase PCA strategy, which enabled analysis of protein-protein interactions between GR and predicted TFs of mammary cells. A library comprising both nuclear receptors (estrogen receptor, mineralocorticoid receptor, GR) and TFs was fused to fragments of GLuc, namely GLuc(1)-X, X-GLuc(1), and X-GLuc(2), where GLuc(1) and GLuc(2) correspond to the N-terminal and C-terminal fragments of the luciferase gene.The resulting library was screened, in human embryonic kidney 293T (HEK293T) cells, for all possible interactions between nuclear receptors and TFs. By screening all of the combinations between TFs and nuclear receptors, we identified several positive interactions, which were strengthened in response to dexamethasone and abolished in response to RU486. Furthermore, the interactions between GR and the candidate TFs were validated by co-immunoprecipitation in MCF10A and in CHLA9 cells. Currently, the roles played by the uncovered interactions are being evaluated in various cellular processes, such as cellular proliferation, migration, and invasion. In conclusion, our assay provides an unbiased network analysis between nuclear receptors and other TFs, which can lead to important insights into transcriptional regulation by nuclear receptors in various diseases, in this case of cancer.

Keywords: epidermal growth factor, glucocorticoid receptor, protein complementation assay, transcription factor

Procedia PDF Downloads 227
4402 Immunoliposome-Mediated Drug Delivery to Plasmodium-Infected and Non-Infected Red Blood Cells as a Dual Therapeutic/Prophylactic Antimalarial Strategy

Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

Abstract:

Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

Procedia PDF Downloads 375
4401 The Game of Dominoes as Teaching-Learning Method of Basic Concepts of Differential Calculus

Authors: Luis Miguel Méndez Díaz

Abstract:

In this article, a mathematics teaching-learning strategy will be presented, specifically differential calculus in one variable, in a fun and competitive space in which the action on the part of the student is manifested and not only the repetition of information on the part of the teacher. Said action refers to motivating, problematizing, summarizing, and coordinating a game of dominoes whose thematic cards are designed around the basic and main contents of differential calculus. The strategies for teaching this area are diverse and precisely the game of dominoes is one of the most used strategies in the practice of mathematics because it stimulates logical reasoning and mental abilities. The objective on this investigation is to identify the way in which the game of dominoes affects the learning and understanding of fundamentals concepts of differential calculus in one variable through experimentation carried out on students of the first semester of the School of Engineering and Sciences of the Technological Institute of Monterrey Campus Querétaro. Finally, the results of this study will be presented and the use of this strategy in other topics around mathematics will be recommended to facilitate logical and meaningful learning in students.

Keywords: collaborative learning, logical-mathematical intelligence, mathematical games, multiple intelligences

Procedia PDF Downloads 84
4400 Savinglife®: An Educational Technology for Basic and Advanced Cardiovascular Life Support

Authors: Naz Najma, Grace T. M. Dal Sasso, Maria de Lourdes de Souza

Abstract:

The development of information and communication technologies and the accessibility of mobile devices has increased the possibilities of the teaching and learning process anywhere and anytime. Mobile and web application allows the production of constructive teaching and learning models in various educational settings, showing the potential for active learning in nursing. The objective of this study was to present the development of an educational technology (Savinglife®, an app) for learning cardiopulmonary resuscitation and advanced cardiovascular life support training. Savinglife® is a technological production, based on the concept of virtual learning and problem-based learning approach. The study was developed from January 2016 to November 2016, using five phases (analyze, design, develop, implement, evaluate) of the instructional systems development process. The technology presented 10 scenarios and 12 simulations, covering different aspects of basic and advanced cardiac life support. The contents can be accessed in a non-linear way leaving the students free to build their knowledge based on their previous experience. Each scenario is presented through interactive tools such as scenario description, assessment, diagnose, intervention and reevaluation. Animated ECG rhythms, text documents, images and videos are provided to support procedural and active learning considering real life situation. Accessible equally on small to large devices with or without an internet connection, Savinglife® offers a dynamic, interactive and flexible tool, placing students at the center of the learning process. Savinglife® can contribute to the student’s learning in the assessment and management of basic and advanced cardiac life support in a safe and ethical way.

Keywords: problem-based learning, cardiopulmonary resuscitation, nursing education, advanced cardiac life support, educational technology

Procedia PDF Downloads 305
4399 Carnatic Music Ragas and Their Role in Music Therapy

Authors: Raghavi Janaswamy, Saraswathi K. Vasudev

Abstract:

Raga, as the soul and base, is a distinctive musical entity, in the music system, with unique structure on its construction of srutis (musical sounds) and application. One of the essential components of the music system is the ‘tala’ that defines the rhythm of a song. There are seven basic swaras (notes) Sa, Ri, Ga, Ma, Pa, Da and Ni in the carnatic music system that are analogous to the C, D, E, F, G, A and B of the western system. The carnatic music further builds on conscious use of microtones, gamakams (oscillation) and rendering styles. It has basic 72 ragas known as melakarta ragas, and a plethora of ragas have been developed from them with permutations and combinations of the basic swaras. Among them, some ragas derived from a same melakarta raga are distinctly different from each other and could evoke a profound difference in the raga bhava (emotion) during rendering. Although these could bear similar arohana and avarohana swaras, their quintessential differences in the gamakas usage and srutis present therein offer varied melodic feelings; variations in the intonation and stress given to certain swara phrases are the root causes. This article enlightens a group of such allied ragas (AR) from the perspectives of their schema and raga alapana (improvisation), ranjaka prayogas (signature phrases), differences in rendering tempo, gamakas and delicate srutis along with the range of sancharas (musical phrases). The intricate differences on the sruti frequencies and use of AR in composing kritis (musical compositions) toward emotive accomplishments such as mood of valor, kindness, love, humor, anger, mercy to name few, have also been explored. A brief review on the existing scientific research on the music therapy on some of the Carnatic ragas is presented. Studying and comprehending the AR, indeed, enable the music aspirants to gain a thorough knowledge on the subtle nuances among the ragas. Such knowledge helps leave a long-lasting melodic impression on the listeners and enable further research on the music therapy.

Keywords: Carnatic music, allied ragas, melakarta, gamakam

Procedia PDF Downloads 198
4398 Development of Ferric Citrate Complex Draw Solute and Its Application for Liquid Product Enrichment through Forward Osmosis

Authors: H. Li, L. Ji, J. Su

Abstract:

Forward osmosis is an emerging technology for separation and has great potential in the concentration of liquid products such as protein, pharmaceutical, and natural products. In pharmacy industry, one of the very tough talks is to concentrate the product in a gentle way since some of the key components may lose bioactivity when exposed to heating or pressurization. Therefore, forward osmosis (FO), which uses inherently existed osmosis pressure instead of externally applied hydraulic pressure, is attractive for pharmaceutical enrichments in a much efficient and energy-saving way. Recently, coordination complexes have been explored as the new class of draw solutes in FO processes due to their bulky configuration and excellent performance in terms of high water flux and low reverse solute flux. Among these coordination complexes, ferric citrate complex with lots of hydrophilic groups and ionic species which make them good solubility and high osmotic pressure in aqueous solution, as well as its low toxicity, has received much attention. However, the chemistry of ferric complexation by citrate is complicated, and disagreement prevails in the literature, especially for the structure of the ferric citrate. In this study, we investigated the chemical reaction with various molar ratio of iron and citrate. It was observed that the ferric citrate complex (Fe-CA2) with molar ratio of 1:1 for iron and citrate formed at the beginning of the reaction, then Fecit would convert to ferric citrate complex at the molar ratio of 1:2 with the proper excess of citrate in the base solution. The structures of the ferric citrate complexes synthesized were systematically characterized by X-ray diffraction (XRD), UV-vis spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and Thermogravimetric analysis (TGA). Fe-CA2 solutions exhibit osmotic pressures more than twice of that for NaCl solutions at the same concentrations. Higher osmotic pressure means higher driving force, and this is preferable for the FO process. Fe-CA2 and NaCl draw solutions were prepared with the same osmotic pressure and used in FO process for BSA protein concentration. Within 180 min, BSA concentration was enriched from 0.2 to 0.27 L using Fe-CA draw solutions. However, it was only increased from 0.20 to 0.22 g/L using NaCl draw solutions. A reverse flux of 11 g/m²h was observed for NaCl draw solutes while it was only 0.1 g/m²h for Fe-CA2 draw solutes. It is safe to conclude that Fe-CA2 is much better than NaCl as draw solute and it is suitable for the enrichment of liquid product.

Keywords: draw solutes, ferric citrate complex, forward osmosis, protein enrichment

Procedia PDF Downloads 153
4397 Estrogen Controls Hepatitis C Virus Entry and Spread through the GPR30 Pathway

Authors: Laura Ulitzky, Dougbeh-Chris Nyan, Manuel M. Lafer, Erica Silberstein, Nicoleta Cehan, Deborah R. Taylor

Abstract:

Hepatitis C virus (HCV)-associated hepatocellular carcinoma, fibrosis and cirrhosis are more frequent in men and postmenopausal women than in premenopausal women and women receiving hormone replacement therapy, suggesting that β-estradiol (estrogen) plays an innate role in preventing viral infection and liver disease. Estrogen classically acts through nuclear estrogen receptors or, alternatively, through the membrane-bound G-protein-coupled estrogen receptor (GPR30 or GPER). We observed a marked decrease in detectable virus when HCV-infected human hepatoma cells were treated with estrogen. The effect was mimicked by both Tamoxifen (Tam) and G1, a GPR30-specific agonist, and was reversed by the GPR30-specific antagonist, G15. Through GPR30, estrogen-mediated the down-regulation of occludin; a tight junction protein and HCV receptor, by promoting activation of matrix metalloproteinases (MMPs). Activated MMP-9 was secreted in response to estrogen, cleaving occludin in the extracellular Domain D, the motif required for HCV entry and spread. This pathway gives new insight into a novel innate immune pathway and the disparate host-virus responses to HCV demonstrated by the two sexes. Moreover, these data suggest that hormone replacement therapy may have beneficial antiviral properties for HCV-infected postmenopausal women and show promise for new antiviral treatments for both men and women.

Keywords: HCV, estrogen, occludin, MMPs

Procedia PDF Downloads 437
4396 Functional Ingredients from Potato By-Products: Innovative Biocatalytic Processes

Authors: Salwa Karboune, Amanda Waglay

Abstract:

Recent studies indicate that health-promoting functional ingredients and nutraceuticals can help support and improve the overall public health, which is timely given the aging of the population and the increasing cost of health care. The development of novel ‘natural’ functional ingredients is increasingly challenging. Biocatalysis offers powerful approaches to achieve this goal. Our recent research has been focusing on the development of innovative biocatalytic approaches towards the isolation of protein isolates from potato by-products and the generation of peptides. Potato is a vegetable whose high-quality proteins are underestimated. In addition to their high proportion in the essential amino acids, potato proteins possess angiotensin-converting enzyme-inhibitory potency, an ability to reduce plasma triglycerides associated with a reduced risk of atherosclerosis, and stimulate the release of the appetite regulating hormone CCK. Potato proteins have long been considered not economically feasible due to the low protein content (27% dry matter) found in tuber (Solanum tuberosum). However, potatoes rank the second largest protein supplying crop grown per hectare following wheat. Potato proteins include patatin (40-45 kDa), protease inhibitors (5-25 kDa), and various high MW proteins. Non-destructive techniques for the extraction of proteins from potato pulp and for the generation of peptides are needed in order to minimize functional losses and enhance quality. A promising approach for isolating the potato proteins was developed, which involves the use of multi-enzymatic systems containing selected glycosyl hydrolase enzymes that synergistically work to open the plant cell wall network. This enzymatic approach is advantageous due to: (1) the use of milder reaction conditions, (2) the high selectivity and specificity of enzymes, (3) the low cost and (4) the ability to market natural ingredients. Another major benefit to this enzymatic approach is the elimination of a costly purification step; indeed, these multi-enzymatic systems have the ability to isolate proteins, while fractionating them due to their specificity and selectivity with minimal proteolytic activities. The isolated proteins were used for the enzymatic generation of active peptides. In addition, they were applied into a reduced gluten cookie formulation as consumers are putting a high demand for easy ready to eat snack foods, with high nutritional quality and limited to no gluten incorporation. The addition of potato protein significantly improved the textural hardness of reduced gluten cookies, more comparable to wheat flour alone. The presentation will focus on our recent ‘proof-of principle’ results illustrating the feasibility and the efficiency of new biocatalytic processes for the production of innovative functional food ingredients, from potato by-products, whose potential health benefits are increasingly being recognized.

Keywords: biocatalytic approaches, functional ingredients, potato proteins, peptides

Procedia PDF Downloads 379
4395 Preparation and Characterization of Calcium Phosphate Cement

Authors: W. Thepsuwan, N. Monmaturapoj

Abstract:

Calcium phosphate cements (CPCs) is one of the most attractive bioceramics due to its moldable and shape ability to fill complicated bony cavities or small dental defect positions. In this study, CPCs were produced by using mixtures of tetracalcium phosphate (TTCP, Ca4O(PO4)2) and dicalcium phosphate anhydrous (DCPA, CaHPO4) in equimolar ratio (1/1) with aqueous solutions of acetic acid (C2H4O2) and disodium hydrogen phosphate dehydrate (Na2HPO4.2H2O) in combination with sodium alginate in order to improve theirs moldable characteristic. The concentrations of the aqueous solutions and sodium alginate were varied to investigate the effects of different aqueous solution and alginate on properties of the cements. The cement paste was prepared by mixing cement powder (P) with aqueous solution (L) in a P/L ratio of 1.0 g/ 0.35 ml. X-ray diffraction (XRD) was used to analyses phase formation of the cements. Setting times and compressive strength of the set CPCs were measured using the Gilmore apparatus and Universal testing machine, respectively. The results showed that CPCs could be produced by using both basic (Na2HPO4.2H2O) and acidic (C2H4O2) solutions. XRD results show the precipitation of hydroxyapatite in all cement samples. No change in phase formation among cements using difference concentrations of Na2HPO4.2H2O solutions. With increasing concentration of acidic solutions, samples obtained less hydroxyapatite with a high dicalcium phosphate dehydrate leaded to a shorter setting time. Samples with sodium alginate exhibited higher crystallization of hydroxyapatite than that of without alginate as a result of shorten setting time in basic solution but a longer setting time in acidic solution. The stronger cement was attained from samples using acidic solution with sodium alginate; however it was lower than using the basic solution.

Keywords: calcium phosphate cements, TTCP, DCPA, hydroxyapatite, properties

Procedia PDF Downloads 390
4394 Biomass and Biogas Yield of Maize as Affected by Nitrogen Rates with Varying Harvesting under Semi-Arid Condition of Pakistan

Authors: Athar Mahmood, Asad Ali

Abstract:

Management considerations including harvesting time and nitrogen application considerably influence the biomass yield, quality and biogas production. Therefore, a field study was conducted to determine the effect of various harvesting times and nitrogen rates on the biomass yield, quality and biogas yield of maize crop. This experiment was consisted of various harvesting times i.e., harvesting after 45, 55 and 65 days of sowing (DAS) and nitrogen rates i.e., 0, 100, 150 and 200 kg ha-1 respectively. The data indicated that maximum plant height, leaf area, dry matter (DM) yield, protein, acid detergent fiber, neutral detergent fiber, crude fiber contents and biogas yield were recorded 65 days after sowing while lowest was recorded 45 days after sowing. In contrary to that significantly higher chlorophyll contents were observed at 45 DAS. In case of nitrogen rates maximum plant height, leaf area, and DM yield, protein contents, ash contents, acid detergent fiber, neutral detergent fiber, crude fiber contents and chlorophyll contents were determined with nitrogen at the rate of 200 kg ha-1, while minimum was observed when no N was applied. Therefore, harvesting 65 DAS and N application @ 200 kg ha-1 can be suitable for getting the higher biomass and biogas production.

Keywords: chemical composition, fiber contents, biogas, nitrogen, harvesting time

Procedia PDF Downloads 160
4393 Protein Stabilized Foam Structures as Protective Carrier Systems during Microwave Drying of Probiotics

Authors: Jannika Dombrowski, Sabine Ambros, Ulrich Kulozik

Abstract:

Due to the increasing popularity of healthy products, probiotics are still of rising importance in food manufacturing. With the aim to amplify the field of probiotic application to non-chilled products, the cultures have to be preserved by drying. Microwave drying has proved to be a suitable technique to achieve relatively high survival rates, resulting from drying at gentle temperatures, among others. However, diffusion limitation due to compaction of cell suspension during drying can prolong drying times as well as deteriorate product properties (grindability, rehydration performance). Therefore, we aimed to embed probiotics in an aerated matrix of whey proteins (surfactants) and di-/polysaccharides (foam stabilization, probiotic protection) during drying. As a result of the manifold increased inner surface of the cell suspension, drying performance was enhanced significantly as compared to non-foamed suspensions. This work comprises investigations on suitable foam matrices, being stable under vacuum (variation of protein concentration, type and concentration of di-/polysaccharide) as well as development of an applicable microwave drying process in terms of microwave power, chamber pressure and maximum product temperatures. Performed analyses included foam characteristics (overrun, drainage, firmness, bubble sizes), and properties of the dried cultures (survival, activity). In addition, efficiency of the drying process was evaluated.

Keywords: foam structure, microwave drying, polysaccharides, probiotics

Procedia PDF Downloads 262
4392 Expression of Fused Plasmodium falciparum Orotate Phosphoribosyltransferase and Orotidine 5'-Monophosphate Decarboxylase in Escherichia coli

Authors: Waranya Imprasittichai, Patsarawadee Paojinda, Sudaratana R. Krungkrai, Nirianne Marie Q. Palacpac, Toshihiro Horii, Jerapan Krungkrai

Abstract:

Fusion of the last two enzymes in the pyrimidine biosynthetic pathway in the inversed order by having COOH-terminal orotate phosphoribosyltransferase (OPRT) and NH2-terminal orotidine 5'-monophosphate decarboxylase (OMPDC), as OMPDC-OPRT, are described in many organisms. In this study, we constructed gene fusions of Plasmodium falciparum OMPDC-OPRT (1,836 bp) in pTrcHisA vector and expressed as an 6xHis-tag bifunctional protein in three Escherichia coli strains (BL21, Rosetta, TOP10) at 18 °C, 25 °C and 37 °C. The recombinant bifunctional protein was partially purified by Ni-Nitrilotriacetic acid-affinity chromatography. Specific activities of OPRT and OMPDC domains in the bifunctional enzyme expressed in E. coli TOP10 cells were approximately 3-4-fold higher than those in BL21 cells. There were no enzymatic activities when the construct vector expressed in Rosetta cells. Maximal expression of the fused gene was observed at 18 °C and the bifunctional enzyme had specific activities of OPRT and OMPDC domains in a ratio of 1:2. These results provide greater yields and better catalytic activities of the bifunctional OMPDC-OPRT enzyme for further purification and kinetic study.

Keywords: bifunctional enzyme, orotate phosphoribosyltransferase, orotidine 5'-monophosphate decarboxylase, plasmodium falciparum

Procedia PDF Downloads 354
4391 Teacher-Student Relationship and Achievement in Chinese: Potential Mediating Effects of Motivation

Authors: Yuan Liu, Hongyun Liu

Abstract:

Teacher-student relationship plays an important role on facilitating students’ learning behavior, school engagement, and academic outcomes. It is believed that good relationship will enhance the human agency—the intrinsic motivation—mainly through the strengthening of autonomic support, feeling of relatedness, and the individual’s competence to increase the academic outcomes. This is in line with self-determination theory (SDT), which generally views that the intrinsic motivation imbedded with human basic needs is one of the most important factors that would lead to better school engagement, academic outcomes, and well-being. Based on SDT, the present study explored the relation of among teacher-student relationship (teacher’s encouragement, respect), students’ motivation (extrinsic and intrinsic), and achievement outcomes. The study was based on a large scale academic assessment and questionnaire survey conducted by the Center for Assessment and Improvement of Basic Education Quality in Mainland China (2013) on Grade 8 students. The results indicated that intrinsic motivation mediated the relation between teacher-student relationship and academic achievement outcomes.

Keywords: teacher-student relationship, intrinsic motivation, academic achievement, mediation

Procedia PDF Downloads 433
4390 A Novel Gene Encoding Ankyrin-Repeat Protein, SHG1, Is Indispensable for Seed Germination under Moderate Salt Stress

Authors: H. Sakamoto, J. Tochimoto, S. Kurosawa, M. Suzuki, S. Oguri

Abstract:

Salt stress adversely affects plant growth at various stages of development including seed germination, seedling establishment, vegetative growth and finally reproduction. Because of their immobile nature, plants have evolved mechanisms to sense and respond to salt stress. Seed dormancy is an adaptive trait that enables seed germination to coincide with favorable environmental conditions. We identified a novel locus of Arabidopsis, designated SHG1 (salt hypersensitive germination 1), whose disruption leads to reduced germination rate under moderate salt stress conditions. SHG1 encodes a transmembrane protein with an ankyrin repeat motif that has been implicated in diverse cellular processes such as signal transduction. The SGH1-disrupted Arabidopsis mutant died at the cotyledon stage when sown on salt-containing medium, although wild type plants could form true leaves under the same conditions. On the other hand, this mutant showed similar phenotypes to wild type plants when sown on medium without salt and transferred to salt-containing medium at the vegetative stage. These results suggested that SHG1 played indispensable role in the seed germination and seedling establishment under moderate salt stress conditions. SHG1 may be involved in the release of seed dormancy.

Keywords: germination, ankyrin repeat, arabidopsis, salt tolerance

Procedia PDF Downloads 398
4389 Perceived Needs on Teaching-Learning Activities among Basic Education Teachers as Reflected in Their In-Service Teacher Training

Authors: Cristie Ann Jaca-Delfin, Felino Javines Jr.

Abstract:

Teachers especially those who are teaching elementary and high school students need to upgrade their teaching practices in order to become effective and efficient facilitators of learning. It is in this context that this study is conducted in order to present the perceived teaching-learning activities needs among basic education teachers in the three campuses of the University of San Carlos, Cebu City, the Philippines as expressed during their In-Service Teacher Training. The study employed the quantitative-qualitative research design and used the researcher-made survey questionnaire to look into the ten items under Teaching-Learning Activities to determine which item teachers need to be trained and retrained on. The data were solicited during the teachers’ In-Service Teacher Training period conducted in May 2015. It was found out that designing interesting and meaningful classroom activities, strategies in teaching and assessment procedures were identified as the most needed areas teachers want to be included in their in-service training. As these expressed needs were identified, the teachers’ in-service training must a venue for teachers’ instructional development needs to be addressed so as to maximize the students’ learning outcomes

Keywords: in-service teacher training, perceived needs, teaching-learning activities, teaching practices

Procedia PDF Downloads 325
4388 Prognostic Value of C-Reactive Protein (CRP) in SARS-CoV-2 Infection: A Simplified Biomarker of COVID-19 Severity in Sub-Saharan Africa

Authors: Teklay Gebrecherkos, Mahmud Abdulkader, Tobias Rinke De Wit, Britta C. Urban, Feyissa Chala, Yazezew Kebede, Dawit Welday

Abstract:

Background: C-reactive protein (CRP) levels are a reliable surrogate for interleukin-6 bioactivity that plays a pivotal role in the pathogenesis of cytokine storm associated with severe COVID-19. There is a lack of data on the role of CRP as a determinant of COVID-19 severity status in the African context. Methods: We determined the longitudinal kinetics of CRP levels on 78 RT-PCR-confirmed COVID-19 patients (49 non-severe and 29 severe cases) and 50 PCR-negative controls. Results: COVID-19 patients had overall significantly elevated CRP at baseline when compared to PCR-negative controls [median 11.1 (IQR: 2.0-127.8) mg/L vs. 0.9 (IQR: 0.5-1.9) mg/L; p=0.0004)]. Moreover, severe COVID-19 patients had significantly higher median CRP levels than non-severe cases [166.1 (IQR: 48.6-332.5) mg/L vs. 2.4 (IQR: 1.2-7.6) mg/L; p<0.00001)]. In addition, persistently elevated levels of CRP were exhibited among those with comorbidities and higher age groups. Area under receiver operating characteristic curve (AUC) analysis of CRP levels distinguished PCR-confirmed COVID-19 patients from the ones with PCR-negative non-COVID-19 individuals, with an AUC value of 0.77 (95% CI: 0.68-0.84; p=0.001). Moreover, it clearly distinguished severe from non-severe COVID-19 patients, with an AUC value of 0.83 (95% CI: 0.73-0.91). After adjusting for age and the presence of comorbidities, CRP levels above 30 mg/L were significantly associated with an increased risk of developing severe COVID-19 (adjusted relative risk 3.99 (95%CI: 1.35-11.82; p=0.013). Conclusions: Determining CRP levels in COVID-19 patients in African settings may provide a simple, prompt, and inexpensive assessment of the severity status at baseline and monitoring of treatment outcomes.

Keywords: CRP, COVID-19, SARS-CoV-2, biomarker

Procedia PDF Downloads 82
4387 Non-Canonical Beclin-1-Independent Autophagy and Apoptosis in Cell Death Induced by Rhus coriaria in Human Colon HT-29 Cancer Cells

Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

Abstract:

Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

Procedia PDF Downloads 262
4386 Helicoverpa armigera Hubner (Lepidoptera: Noctuidae) Susceptibility to Bacillus thuringiensis Crystal Toxins

Authors: Muhammad Jawad Saleem, Faisal Hafeez, Muhammad Arshad, Afifa Naeem, Ayesha Iftekhar

Abstract:

Bacillus thuringiensis is a gram-positive spore-forming bacterium that belongs to the Bacillus cereus group of Bacilli and it produces ICP (insecticidal crystal protein) Cry toxins or Cysts toxins. Spores are produced as parasporal crystalline inclusions bodies (also known as endotoxins) at the onset of sporulation during the stationary growth phase. During vegetative growth that does not form crystals and is called vegetative insecticidal proteins (VIP) and secreted an insecticidal protein (SIP). Bacillus thuringiensis (Bt) is important for pest management either in the form of insecticides or through incorporated in the gene of the crop. Bioassays were conducted on the F2 generation of 1st instar larvae of H. armigera by the diet incorporation method to determine the susceptibility to Bt Cry toxins (Cry1Ac, Cry2Ab, Cry2A). The median lethal concentration (LC₅₀) of Cry1Ac, Cry2Ab, Cry2A ranged from 0.11 to 1.06 µg/ml and moult inhibitory concentration (MIC₅₀) of Cry1Ac, Cry2Ab, Cry2A ranged from 0.05 to 0.25 µg/ml. Cry1Ac was found most toxic to 1st instar larvae of H. armigera as compared to other Bt Cry toxins (Cry1Ac, Cry2Ab, Cry2A). The experimental results are important to policy-makers and technology providers to develop strategies for the exploitation of transgenic Bt cotton varieties as a component of integrated pest management.

Keywords: Bt toxin, Cry1Ac, Cry2Ab, Cry2A, susceptibility, Helicoverpa armigera

Procedia PDF Downloads 178
4385 The Second Generation of Tyrosine Kinase Inhibitor Afatinib Controls Inflammation by Regulating NLRP3 Inflammasome Activation

Authors: Shujun Xie, Shirong Zhang, Shenglin Ma

Abstract:

Background: Chronic inflammation might lead to many malignancies, and inadequate resolution could play a crucial role in tumor invasion, progression, and metastases. A randomised, double-blind, placebo-controlled trial shows that IL-1β inhibition with canakinumab could reduce incident lung cancer and lung cancer mortality in patients with atherosclerosis. The process and secretion of proinflammatory cytokine IL-1β are controlled by the inflammasome. Here we showed the correlation of the innate immune system and afatinib, a tyrosine kinase inhibitor targeting epidermal growth factor receptor (EGFR) in non-small cell lung cancer. Methods: Murine Bone marrow derived macrophages (BMDMs), peritoneal macrophages (PMs) and THP-1 were used to check the effect of afatinib on the activation of NLRP3 inflammasome. The assembly of NLRP3 inflammasome was check by co-immunoprecipitation of NLRP3 and apoptosis-associated speck-like protein containing CARD (ASC), disuccinimidyl suberate (DSS)-cross link of ASC. Lipopolysaccharide (LPS)-induced sepsis and Alum-induced peritonitis were conducted to confirm that afatinib could inhibit the activation of NLRP3 in vivo. Peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) patients before or after taking afatinib were used to check that afatinib inhibits inflammation in NSCLC therapy. Results: Our data showed that afatinib could inhibit the secretion of IL-1β in a dose-dependent manner in macrophage. Moreover, afatinib could inhibit the maturation of IL-1β and caspase-1 without affecting the precursors of IL-1β and caspase-1. Next, we found that afatinib could block the assembly of NLRP3 inflammasome and the ASC speck by blocking the interaction of the sensor protein NLRP3 and the adaptor protein ASC. We also found that afatinib was able to alleviate the LPS-induced sepsis in vivo. Conclusion: Our study found that afatinib could inhibit the activation of NLRP3 inflammasome in macrophage, providing new evidence that afatinib could target the innate immune system to control chronic inflammation. These investigations will provide significant experimental evidence in afatinib as therapeutic drug for non-small cell lung cancer or other tumors and NLRP3-related diseases and will explore new targets for afatinib.

Keywords: inflammasome, afatinib, inflammation, tyrosine kinase inhibitor

Procedia PDF Downloads 118