Search results for: O-antigen gene cluster
Commenced in January 2007
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Paper Count: 2252

Search results for: O-antigen gene cluster

182 Stilbenes as Sustainable Antimicrobial Compounds to Control Vitis Vinifera Diseases

Authors: David Taillis, Oussama Becissa, Julien Gabaston, Jean-Michel Merillon, Tristan Richard, Stephanie Cluzet

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Nowadays, there is a strong pressure to reduce the phytosanitary inputs of synthetic chemistry in vineyards. It is, therefore, necessary to find viable alternatives in order to protect the vine against its major diseases. For this purpose, we suggest the use of a plant extract enriched in antimicrobial compounds. Being produced from vine trunks and roots, which are co-products of wine production, the extract produced is part of a circular economy. The antimicrobial molecules present in this plant material are polyphenols and, more particularly, stilbenes, which are derived from a common base, the resveratrol unit, and that are well known vine phytoalexins. The stilbenoids were extracted from trunks and roots (30/70, w/w) by a double extraction with ethyl acetate followed by enrichment by liquid-liquid extraction. The produced extract was characterized by UHPLC-MS, then its antimicrobial activities were tested on Plasmopara viticola and Botrytis cinerea in the laboratory and/or in greenhouse and in vineyard. The major compounds were purified, and their antimicrobial activity was evaluated on B. cinerea. Moreover, after its spraying, the effect of the stilbene extract on the plant defence status was evaluated by analysis of defence gene expression. UHPLC-MS analysis revealed that the extract contains 50% stilbenes with resveratrol, ε-viniferin and r-viniferin as major compounds. The extract showed antimicrobial activities on P. viticola with IC₅₀ and IC₁₀₀ respectively of 90 and 300 mg/L in the laboratory. In addition, it inhibited 40% of downy mildew development in greenhouse. However, probably because of the sensitivity of stilbenes to the environment, such as UV degradation, no activity has been observed in vineyard towards P. viticola development. For B. cinerea, the extract IC50 was 123 mg/L, with resveratrol and ε-viniferin being the most active stilbenes (IC₅₀ of 88 and 142 mg/L, respectively). The analysis of the expression of defence genes revealed that the extract can induce the expression of some defence genes 24, 48, and 72 hours after treatment, meaning that the extract has a defence-stimulating effect at least for the first three days after treatment. In conclusion, we produced a plant extract enriched in stilbenes with antimicrobial properties against two major grapevine pathogenic agents P. viticola and B. cinerea. In addition, we showed that this extract displayed eliciting activity of plant defences. This extract can therefore represent, after formulation development, a viable eco-friendly alternative for vineyard protection. Subsequently, the effect of the stilbenoid extract on primary metabolism will be evaluated by quantitative NMR.

Keywords: antimicrobial, bioprotection, grapevine, Plasmopara viticola, stilbene

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181 Investigation of Azol Resistance in Aspergillosis Caused by Gradient Test and Agar Plaque Methods

Authors: Zeynep Yazgan, Gökhan Aygün, Reyhan Çalışkan

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Objective: Invasive fungal infections are a serious threat in terms of morbidity and mortality, especially in immunocompromised patients. The most frequently isolated agents are Aspergillus genus fungi, and sensitivity to azoles, which are the first choice in treatment, decreases. In our study, we aimed to investigate the use of the agar plate screening method as a fast, easy, and practical method in determining azole resistance in Aspergillus spp. species. Methods: Our study was conducted with 125 Aspergillus spp. isolates produced from various clinical samples. Aspergillus spp. isolates were identified by conventional methods and azole resistance was determined by gradient test and agar plate screening method. Broth microdilution method was applied to resistant isolates, and CypA-L98H and CypA-M220 mutations in the cyp51A gene were investigated. Results: In our study, 55 A. fumigatus complex (44%), 42 A. flavus (33.6%), 6 A. terreus (5%), 4 A. niger (3%) and 18 Aspergillus spp. (14%) were identified. With the gradient test method, resistance to VOR and POS was detected in 1 (1.8%) of A.fumigatus isolates, and resistance to ITR was detected in 3 (5.45%). With the agar plate method, 1 of the A.fumigatus isolates (1.8%) had VOR, ITR, POS, 1 of the A.terreus isolates (16.7%) had VOR, 1 of the A.niger isolates (25%) had ITR. Resistance to VOR and POS was detected in 2 Aspergillus spp. isolates (11%), and resistance to ITR was detected in 1 (5.6%). Sensitivity and specificity were determined as 100% for VOR and POS in A. fumigatus species, 33.3% and 100% for ITR, respectively, 100% for ITR in A. flavus species, and 100% for ITR and POS in A. terreus species. By broth microdilution method in 7 isolates in which resistance was detected by gradient test and/or agar plate screening method; 1 A.fumigatus resistant to ITR, VOR, POS, 2 A.fumigatus resistant to ITR, 2 Aspergillus spp. ITR, VOR, POS MICs were determined as 2µg/ml and 8µg/ml, 8µg/ml and >32µg/ml, 0.5µg/ml and 4µg/ml, respectively. CypA-L98H mutations were detected in 5 of these isolates, CypA-M220 mutations were detected in 6, and no mutation was detected in 1. CypA-L98H and CypA-M220 mutations were detected in 1 isolate for which resistance was not detected. Conclusion: The need for rapid antifungal susceptibility screening tests is increasing in the treatment of aspergillosis. Although the sensitivity of the agar plate method was determined to be 33.3% for A.fumigatus ITR in our study, its sensitivity and specificity were determined to be 100% for ITR, VOR, and POS in other species. The low sensitivity value detected for A.fumigatus showed that agar plate drug concentrations should be updated in accordance with the latest regulations of EUCAST guidelines. The CypA-L98H and CypA-M220 mutations detected in our study suggested that the distribution of azole resistance-related mutations in different regions in our country should be investigated. In conclusion, it is thought that the agar plate method, which can be easily applied to detect azole resistance, is a fast and practical method in routine use and can contribute to both the determination of effective treatment strategies and the generation of epidemiological data.

Keywords: Aspergillus, agar plate, azole resistance, cyp51A, cypA-L98H, cypA-M220

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180 The Effect of Slum Neighborhoods on Pregnancy Outcomes in Tanzania: Secondary Analysis of the 2015-2016 Tanzania Demographic and Health Survey Data

Authors: Luisa Windhagen, Atsumi Hirose, Alex Bottle

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Global urbanization has resulted in the expansion of slums, leaving over 10 million Tanzanians in urban poverty and at risk of poor health. Whilst rural residence has historically been associated with an increased risk of adverse pregnancy outcomes, recent studies found higher perinatal mortality rates in urban Tanzania. This study aims to understand to what extent slum neighborhoods may account for the spatial disparities seen in Tanzania. We generated a slum indicator based on UN-HABITAT criteria to identify slum clusters within the 2015-2016 Tanzania Demographic and Health Survey. Descriptive statistics, disaggregated by urban slum, urban non-slum, and rural areas, were produced. Simple and multivariable logistic regression examined the association between cluster residence type and neonatal mortality and stillbirth. For neonatal mortality, we additionally built a multilevel logistic regression model, adjusting for confounding and clustering. The neonatal mortality ratio was highest in slums (38.3 deaths per 1000 live births); the stillbirth rate was three times higher in slums (32.4 deaths per 1000 births) than in urban non-slums. Neonatal death was more likely to occur in slums than in urban non-slums (aOR=2.15, 95% CI=1.02-4.56) and rural areas (aOR=1.78, 95% CI=1.15-2.77). Odds of stillbirth were over five times higher among rural than urban non-slum residents (aOR=5.25, 95% CI=1.31-20.96). The results suggest that slums contribute to the urban disadvantage in Tanzanian neonatal health. Higher neonatal mortality in slums may be attributable to lack of education, lower socioeconomic status, poor healthcare access, and environmental factors, including indoor and outdoor air pollution and unsanitary conditions from inadequate housing. However, further research is required to ascertain specific causalities as well as significant associations between residence type and other pregnancy outcomes. The high neonatal mortality, stillbirth, and slum formation rates in Tanzania signify that considerable change is necessary to achieve international goals for health and human settlements. Disparities in access to adequate housing, safe water and sanitation, high standard antenatal, intrapartum, and neonatal care, and maternal education need to urgently be addressed. This study highlights the spatial neonatal mortality shift from rural settings to urban informal settlements in Tanzania. Importantly, other low- and middle-income countries experiencing overwhelming urbanization and slum expansion may also be at risk of a reversing trend in residential neonatal health differences.

Keywords: urban health, slum residence, neonatal mortality, stillbirth, global urbanisation

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179 Neuro-Epigenetic Changes on Diabetes Induced-Synaptic Fidelity in Brain

Authors: Valencia Fernandes, Dharmendra Kumar Khatri, Shashi Bala Singh

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Background and Aim: Epigenetics are the inaudible signatures of several pathological processes in the brain. This study understands the influence of DNA methylation, a major epigenetic modification, in the prefrontal cortex and hippocampus of the diabetic brain and its notable effect on the cellular chaperones and synaptic proteins. Method: Chronic high fat diet and STZ-induced diabetic mice were studied for cognitive dysfunction, and global DNA methylation, as well as DNA methyltransferase (DNMT) activity, were assessed. Further, the cellular chaperones and synaptic proteins were examined using DNMT inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC)-via intracerebroventricular injection. Moreover, % methylation of these synaptic proteins were also studied so as to correlate its epigenetic involvement. Computationally, its interaction with the DNMT enzyme were also studied using bioinformatic tools. Histological studies for morphological alterations and neuronal degeneration were also studied. Neurogenesis, a characteristic marker for new learning and memory formation, was also assessed via the BrdU staining. Finally, the most important behavioral studies, including the Morris water maze, Y maze, passive avoidance, and Novel object recognition test, were performed to study its cognitive functions. Results: Altered global DNA methylation and increased levels of DNMTs within the nucleus were confirmed in the cortex and hippocampus of the diseased mice, suggesting hypermethylation at a genetic level. Treatment with AzadC, a global DNA demethylating agent, ameliorated the protein and gene expression of the cellular chaperones and synaptic fidelity. Furthermore, the methylation analysis profile showed hypermethylation of the hsf1 protein, a master regulator for chaperones and thus, confirmed the epigenetic involvement in the diseased brain. Morphological improvements and decreased neurodegeneration, along with enhanced neurogenesis in the treatment group, suggest that epigenetic modulations do participate in learning and memory. This is supported by the improved behavioral test battery seen in the treatment group. Conclusion: DNA methylation could possibly accord in dysregulating the memory-associated proteins at chronic stages in type 2 diabetes. This could suggest a substantial contribution to the underlying pathophysiology of several metabolic syndromes like insulin resistance, obesity and also participate in transitioning this damage centrally, such as cognitive dysfunction.

Keywords: epigenetics, cognition, chaperones, DNA methylation

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178 The Data Quality Model for the IoT based Real-time Water Quality Monitoring Sensors

Authors: Rabbia Idrees, Ananda Maiti, Saurabh Garg, Muhammad Bilal Amin

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IoT devices are the basic building blocks of IoT network that generate enormous volume of real-time and high-speed data to help organizations and companies to take intelligent decisions. To integrate this enormous data from multisource and transfer it to the appropriate client is the fundamental of IoT development. The handling of this huge quantity of devices along with the huge volume of data is very challenging. The IoT devices are battery-powered and resource-constrained and to provide energy efficient communication, these IoT devices go sleep or online/wakeup periodically and a-periodically depending on the traffic loads to reduce energy consumption. Sometime these devices get disconnected due to device battery depletion. If the node is not available in the network, then the IoT network provides incomplete, missing, and inaccurate data. Moreover, many IoT applications, like vehicle tracking and patient tracking require the IoT devices to be mobile. Due to this mobility, If the distance of the device from the sink node become greater than required, the connection is lost. Due to this disconnection other devices join the network for replacing the broken-down and left devices. This make IoT devices dynamic in nature which brings uncertainty and unreliability in the IoT network and hence produce bad quality of data. Due to this dynamic nature of IoT devices we do not know the actual reason of abnormal data. If data are of poor-quality decisions are likely to be unsound. It is highly important to process data and estimate data quality before bringing it to use in IoT applications. In the past many researchers tried to estimate data quality and provided several Machine Learning (ML), stochastic and statistical methods to perform analysis on stored data in the data processing layer, without focusing the challenges and issues arises from the dynamic nature of IoT devices and how it is impacting data quality. A comprehensive review on determining the impact of dynamic nature of IoT devices on data quality is done in this research and presented a data quality model that can deal with this challenge and produce good quality of data. This research presents the data quality model for the sensors monitoring water quality. DBSCAN clustering and weather sensors are used in this research to make data quality model for the sensors monitoring water quality. An extensive study has been done in this research on finding the relationship between the data of weather sensors and sensors monitoring water quality of the lakes and beaches. The detailed theoretical analysis has been presented in this research mentioning correlation between independent data streams of the two sets of sensors. With the help of the analysis and DBSCAN, a data quality model is prepared. This model encompasses five dimensions of data quality: outliers’ detection and removal, completeness, patterns of missing values and checks the accuracy of the data with the help of cluster’s position. At the end, the statistical analysis has been done on the clusters formed as the result of DBSCAN, and consistency is evaluated through Coefficient of Variation (CoV).

Keywords: clustering, data quality, DBSCAN, and Internet of things (IoT)

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177 Date Palm Fruits from Oman Attenuates Cognitive and Behavioral Defects and Reduces Inflammation in a Transgenic Mice Model of Alzheimer's Disease

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

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Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Date palm fruits contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani date palm fruits on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% Date palm fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analyzed. APPsw/Tg2576 mice that were fed a standard chow diet without dates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, PPsw/Tg2576 mice that were fed a diet containing 2% and 4% dates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Our results suggest that dietary supplementation with dates may slow the progression of cognitive and behavioral impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, date palm fruits, Oman, cognitive decline, memory loss, anxiety, inflammation

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176 Cyclocoelids (Trematoda: Echinostomata) from Gadwall Mareca strepera in the South of the Russian Far East

Authors: Konstantin S. Vainutis, Mark E. Andreev, Anastasia N. Voronova, Mikhail Yu. Shchelkanov

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Introduction: The trematodes from the family Cyclocoelidae (cyclocoelids) belong to the superfamily Echinostomatoidea infecting air sacs and trachea of wild birds. At present, the family Cyclocoelidae comprises nine valid genera in three subfamilies: Cyclocoelinae (type taxon), Haematotrephinae, and Typhlocoelinae. To our best knowledge, in this study, molecular genetic methods were used for the first time for studying cyclocoelids from the Russian Far East. Here we provide the data on the morphology and phylogeny of cyclocoelids from gadwall from the Russian Far East. The morphological and genetic data obtained for cyclocoelids indicated the necessity to revise the previously proposed classification within the family Cyclocoelidae. Objectives: The first objective was performing the morphological study of cyclocoelids found in M. strepera from the Russian Far East. The second objective is to reconstruct the phylogenetic relationships of the studied trematodes with other cyclocoelids using the 28S gene. Material and methods: During the field studies in the Khasansky district of the Primorsky region, 21 cyclocoelids were recovered from the air sacs of a single gadwall Mareca strepera. Seven samples of cyclocoelids were overstained in alum carmine, dehydrated in a graded ethanol series, cleared in clove oil, and mounted in Canada balsam. Genomic DNA was extracted from four cyclocoelids using the alkaline lysis method HotShot. The 28S rDNA fragment was amplified using the forward primer Digl2 and the reverse primer 1500R. Results: According to morphological features (ovary intratesticular, forming a triangle with the testes), the studied worms belong to the subfamily Cyclocoelinae Stossich, 1902. In particular, the highest morphological similarity was observed in relation to the trematodes of the genus Cyclocoelum Brandes, 1892 – genital pores are pharyngeal. However, the genetic analysis has shown significant discrepancies between the trematodes studied regarding the genus Cyclocoelum. On the phylogenetic tree, these trematodes took the sister position in relation to the genus Morishitium (previously considered in the subfamily Szidatitrematinae). Conclusion: Based on the results of the morphological and genetic studies, cyclocoelids isolated from Mareca strepera are suggested to be described in the previously unknown genus and differentiated from the type genus Cyclocoelum of the type subfamily Cyclocoelinae. Considering the available molecular data, including described cyclocoelids, the family Cyclocoelidae comprises ten valid genera in the three subfamilies mentioned above.

Keywords: new species, trematoda, phylogeny, cyclocoelidae

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175 Predictors of Sexually Transmitted Infection of Korean Adolescent Females: Analysis of Pooled Data from Korean Nationwide Survey

Authors: Jaeyoung Lee, Minji Je

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Objectives: In adolescence, adolescents are curious about sex, but sexual experience before becoming an adult can cause the risk of high probability of sexually transmitted infection. Therefore, it is very important to prevent sexually transmitted infections so that adolescents can grow in healthy and upright way. Adolescent females, especially, have sexual behavior distinguished from that of male adolescents. Protecting female adolescents’ reproductive health is even more important since it is directly related to the childbirth of the next generation. This study, thus, investigated the predictors of sexually transmitted infection in adolescent females with sexual experiences based on the National Health Statistics in Korea. Methods: This study was conducted based on the National Health Statistics in Korea. The 11th Korea Youth Behavior Web-based Survey in 2016 was conducted in the type of anonymous self-reported survey in order to find out the health behavior of adolescents. The target recruitment group was middle and high school students nationwide as of April 2016, and 65,528 students from a total of 800 middle and high schools participated. The study was conducted in 537 female high school students (Grades 10–12) among them. The collected data were analyzed as complex sampling design using SPSS statistics 22. The strata, cluster, weight, and finite population correction provided by Korea Center for Disease Control & Prevention (KCDC) were reflected to constitute complex sample design files, which were used in the statistical analysis. The analysis methods included Rao-Scott chi-square test, complex samples general linear model, and complex samples multiple logistic regression analysis. Results: Out of 537 female adolescents, 11.9% (53 adolescents) had experiences of venereal infection. The predictors for venereal infection of the subjects were ‘age at first intercourse’ and ‘sexual intercourse after drinking’. The sexually transmitted infection of the subjects was decreased by 0.31 times (p=.006, 95%CI=0.13-0.71) for middle school students and 0.13 times (p<.001, 95%CI=0.05-0.32) for high school students whereas the age of the first sexual experience was under elementary school age. In addition, the sexually transmitted infection of the subjects was 3.54 times (p < .001, 95%CI=1.76-7.14) increased when they have experience of sexual relation after drinking alcohol, compared to those without the experience of sexual relation after drinking alcohol. Conclusions: The female adolescents had high probability of sexually transmitted infection if their age for the first sexual experience was low. Therefore, the female adolescents who start sexual experience earlier shall have practical sex education appropriate for their developmental stage. In addition, since the sexually transmitted infection increases, if they have sexual relations after drinking alcohol, the consideration for prevention of alcohol use or intervention of sex education shall be required. When health education intervention is conducted for health promotion for female adolescents in the future, it is necessary to reflect the result of this study.

Keywords: adolescent, coitus, female, sexually transmitted diseases

Procedia PDF Downloads 172
174 Regional Dynamics of Innovation and Entrepreneurship in the Optics and Photonics Industry

Authors: Mustafa İlhan Akbaş, Özlem Garibay, Ivan Garibay

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The economic entities in innovation ecosystems form various industry clusters, in which they compete and cooperate to survive and grow. Within a successful and stable industry cluster, the entities acquire different roles that complement each other in the system. The universities and research centers have been accepted to have a critical role in these systems for the creation and development of innovations. However, the real effect of research institutions on regional economic growth is difficult to assess. In this paper, we present our approach for the identification of the impact of research activities on the regional entrepreneurship for a specific high-tech industry: optics and photonics. The optics and photonics has been defined as an enabling industry, which combines the high-tech photonics technology with the developing optics industry. The recent literature suggests that the growth of optics and photonics firms depends on three important factors: the embedded regional specializations in the labor market, the research and development infrastructure, and a dynamic small firm network capable of absorbing new technologies, products and processes. Therefore, the role of each factor and the dynamics among them must be understood to identify the requirements of the entrepreneurship activities in optics and photonics industry. There are three main contributions of our approach. The recent studies show that the innovation in optics and photonics industry is mostly located around metropolitan areas. There are also studies mentioning the importance of research center locations and universities in the regional development of optics and photonics industry. These studies are mostly limited with the number of patents received within a short period of time or some limited survey results. Therefore the first contribution of our approach is conducting a comprehensive analysis for the state and recent history of the photonics and optics research in the US. For this purpose, both the research centers specialized in optics and photonics and the related research groups in various departments of institutions (e.g. Electrical Engineering, Materials Science) are identified and a geographical study of their locations is presented. The second contribution of the paper is the analysis of regional entrepreneurship activities in optics and photonics in recent years. We use the membership data of the International Society for Optics and Photonics (SPIE) and the regional photonics clusters to identify the optics and photonics companies in the US. Then the profiles and activities of these companies are gathered by extracting and integrating the related data from the National Establishment Time Series (NETS) database, ES-202 database and the data sets from the regional photonics clusters. The number of start-ups, their employee numbers and sales are some examples of the extracted data for the industry. Our third contribution is the utilization of collected data to investigate the impact of research institutions on the regional optics and photonics industry growth and entrepreneurship. In this analysis, the regional and periodical conditions of the overall market are taken into consideration while discovering and quantifying the statistical correlations.

Keywords: entrepreneurship, industrial clusters, optics, photonics, emerging industries, research centers

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173 Combination of Unmanned Aerial Vehicle and Terrestrial Laser Scanner Data for Citrus Yield Estimation

Authors: Mohammed Hmimou, Khalid Amediaz, Imane Sebari, Nabil Bounajma

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Annual crop production is one of the most important macroeconomic indicators for the majority of countries around the world. This information is valuable, especially for exporting countries which need a yield estimation before harvest in order to correctly plan the supply chain. When it comes to estimating agricultural yield, especially for arboriculture, conventional methods are mostly applied. In the case of the citrus industry, the sale before harvest is largely practiced, which requires an estimation of the production when the fruit is on the tree. However, conventional method based on the sampling surveys of some trees within the field is always used to perform yield estimation, and the success of this process mainly depends on the expertise of the ‘estimator agent’. The present study aims to propose a methodology based on the combination of unmanned aerial vehicle (UAV) images and terrestrial laser scanner (TLS) point cloud to estimate citrus production. During data acquisition, a fixed wing and rotatory drones, as well as a terrestrial laser scanner, were tested. After that, a pre-processing step was performed in order to generate point cloud and digital surface model. At the processing stage, a machine vision workflow was implemented to extract points corresponding to fruits from the whole tree point cloud, cluster them into fruits, and model them geometrically in a 3D space. By linking the resulting geometric properties to the fruit weight, the yield can be estimated, and the statistical distribution of fruits size can be generated. This later property, which is information required by importing countries of citrus, cannot be estimated before harvest using the conventional method. Since terrestrial laser scanner is static, data gathering using this technology can be performed over only some trees. So, integration of drone data was thought in order to estimate the yield over a whole orchard. To achieve that, features derived from drone digital surface model were linked to yield estimation by laser scanner of some trees to build a regression model that predicts the yield of a tree given its features. Several missions were carried out to collect drone and laser scanner data within citrus orchards of different varieties by testing several data acquisition parameters (fly height, images overlap, fly mission plan). The accuracy of the obtained results by the proposed methodology in comparison to the yield estimation results by the conventional method varies from 65% to 94% depending mainly on the phenological stage of the studied citrus variety during the data acquisition mission. The proposed approach demonstrates its strong potential for early estimation of citrus production and the possibility of its extension to other fruit trees.

Keywords: citrus, digital surface model, point cloud, terrestrial laser scanner, UAV, yield estimation, 3D modeling

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172 Oral Microbiota as a Novel Predictive Biomarker of Response To Immune Checkpoint Inhibitors in Advanced Non-small Cell Lung Cancer Patients

Authors: Francesco Pantano, Marta Fogolari, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Marco Russano, Fabrizio Citarella, Bruno Vincenzi, Silvia Angeletti, Giuseppe Tonini

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Background: Although immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of non–small cell lung cancer (NSCLC), these drugs fail to elicit durable responses in the majority of NSCLC patients. The gut microbiota, able to regulate immune responsiveness, is emerging as a promising, modifiable target to improve ICIs response rates. Since the oral microbiome has been demonstrated to be the primary source of bacterial microbiota in the lungs, we investigated its composition as a potential predictive biomarker to identify and select patients who could benefit from immunotherapy. Methods: Thirty-five patients with stage IV squamous and non-squamous cell NSCLC eligible for an anti-PD-1/PD-L1 as monotherapy were enrolled. Saliva samples were collected from patients prior to the start of treatment, bacterial DNA was extracted using the QIAamp® DNA Microbiome Kit (QIAGEN) and the 16S rRNA gene was sequenced on a MiSeq sequencing instrument (Illumina). Results: NSCLC patients were dichotomized as “Responders” (partial or complete response) and “Non-Responders” (progressive disease), after 12 weeks of treatment, based on RECIST criteria. A prevalence of the phylum Candidatus Saccharibacteria was found in the 10 responders compared to non-responders (abundance 5% vs 1% respectively; p-value = 1.46 x 10-7; False Discovery Rate (FDR) = 1.02 x 10-6). Moreover, a higher prevalence of Saccharibacteria Genera Incertae Sedis genus (belonging to the Candidatus Saccharibacteria phylum) was observed in "responders" (p-value = 6.01 x 10-7 and FDR = 2.46 x 10-5). Finally, the patients who benefit from immunotherapy showed a significant abundance of TM7 Phylum Sp Oral Clone FR058 strain, member of Saccharibacteria Genera Incertae Sedis genus (p-value = 6.13 x 10-7 and FDR=7.66 x 10-5). Conclusions: These preliminary results showed a significant association between oral microbiota and ICIs response in NSCLC patients. In particular, the higher prevalence of Candidatus Saccharibacteria phylum and TM7 Phylum Sp Oral Clone FR058 strain in responders suggests their potential immunomodulatory role. The study is still ongoing and updated data will be presented at the congress.

Keywords: oral microbiota, immune checkpoint inhibitors, non-small cell lung cancer, predictive biomarker

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171 Assessment of Socio-Cultural Sustainability: A Comparative Analysis of Two Neighborhoods in Kolkata Metropolitan Area

Authors: Tanima Bhattacharya, Joy Sen

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To transform a space into a better livable and sustainable zone, United Nations Summit in New York 2015, has decided upon 17 sustainable development goals (SDGs) that approach directly to achieve inclusive, people-centric, sustainable developments. Though sustainability has been majorly constructed by four pillars, namely, Ecological, Economic, Social and Cultural, but it is essentially reduced to economic and ecological consideration in the context of developing countries. Therefore, in most cases planning has reduced its ambit to concentrate around the tangible infrastructure, ignoring the fundamentals of socio-cultural heritage. With the accentuating hype of infrastructural augmentation, lack of emphasis of traditional concerns like ethnicity and social connection have further diluted the situation, disintegrating cultural continuity. As cultural continuity lacks its cohesion, it’s growing absence increasingly acts as a catalyst to degrade the heritage structures, spaces around and linking these structures, and the ability of stakeholders in identifying themselves rooted in that particular space. Hence, this paper will argue that sustainability depends on the people and their interaction with their surroundings, their culture and livelihood. The interaction between people and their surroundings strengthen community building and social interaction that abides by stakeholders reverting back to their roots. To assess the socio-cultural sustainability of the city of Kolkata, two study areas are selected, namely, an old settlement from the northern part of the city of Kolkata (KMA), imbued with social connection, age-old cultural and ethnic bonding and, another cluster of new high-rises coming up in the Newtown area having portions of planned city extension on the eastern side of the city itself. Whereas, Newtown prioritizes the surging post-industrial trends of economic aspiration and ecological aspects of urban sustainability; the former settlements of northern Kolkata still continue to represent the earliest community settlement of the British-colonial-cum native era and even the pre-colonial era, permeated with socio-cultural reciprocation. Thus, to compare and assess the inlayed organizational structure of both the spaces in the two cases, selected areas have been surveyed to portray their current imageability. The argument of this paper is structured in 5parts. First, an introduction of the idea has been forwarded, Secondly, a literature review has been conducted to ground the proposed ideas, Thirdly, methodology has been discussed and appropriate case study areas have been selected, Fourthly, surveys and analyses has been forwarded and lastly, the paper has arrived at a set of conclusions by suggesting a threefold development to create happy, healthy and sustainable community.

Keywords: art innovation, current scenario assessment, heritage, imageability, socio-cultural sustainability

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170 Estimating Estimators: An Empirical Comparison of Non-Invasive Analysis Methods

Authors: Yan Torres, Fernanda Simoes, Francisco Petrucci-Fonseca, Freddie-Jeanne Richard

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The non-invasive samples are an alternative of collecting genetic samples directly. Non-invasive samples are collected without the manipulation of the animal (e.g., scats, feathers and hairs). Nevertheless, the use of non-invasive samples has some limitations. The main issue is degraded DNA, leading to poorer extraction efficiency and genotyping. Those errors delayed for some years a widespread use of non-invasive genetic information. Possibilities to limit genotyping errors can be done using analysis methods that can assimilate the errors and singularities of non-invasive samples. Genotype matching and population estimation algorithms can be highlighted as important analysis tools that have been adapted to deal with those errors. Although, this recent development of analysis methods there is still a lack of empirical performance comparison of them. A comparison of methods with dataset different in size and structure can be useful for future studies since non-invasive samples are a powerful tool for getting information specially for endangered and rare populations. To compare the analysis methods, four different datasets used were obtained from the Dryad digital repository were used. Three different matching algorithms (Cervus, Colony and Error Tolerant Likelihood Matching - ETLM) are used for matching genotypes and two different ones for population estimation (Capwire and BayesN). The three matching algorithms showed different patterns of results. The ETLM produced less number of unique individuals and recaptures. A similarity in the matched genotypes between Colony and Cervus was observed. That is not a surprise since the similarity between those methods on the likelihood pairwise and clustering algorithms. The matching of ETLM showed almost no similarity with the genotypes that were matched with the other methods. The different cluster algorithm system and error model of ETLM seems to lead to a more criterious selection, although the processing time and interface friendly of ETLM were the worst between the compared methods. The population estimators performed differently regarding the datasets. There was a consensus between the different estimators only for the one dataset. The BayesN showed higher and lower estimations when compared with Capwire. The BayesN does not consider the total number of recaptures like Capwire only the recapture events. So, this makes the estimator sensitive to data heterogeneity. Heterogeneity in the sense means different capture rates between individuals. In those examples, the tolerance for homogeneity seems to be crucial for BayesN work properly. Both methods are user-friendly and have reasonable processing time. An amplified analysis with simulated genotype data can clarify the sensibility of the algorithms. The present comparison of the matching methods indicates that Colony seems to be more appropriated for general use considering a time/interface/robustness balance. The heterogeneity of the recaptures affected strongly the BayesN estimations, leading to over and underestimations population numbers. Capwire is then advisable to general use since it performs better in a wide range of situations.

Keywords: algorithms, genetics, matching, population

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169 Fatty Acid Translocase (Cd36), Energy Substrate Utilization, and Insulin Signaling in Brown Adipose Tissue in Spontaneously Hypertensive Rats

Authors: Michal Pravenec, Miroslava Simakova, Jan Silhavy

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Brown adipose tissue (BAT) plays an important role in lipid and glucose metabolism in rodents and possibly also in humans. Recently, using systems genetics approach in the BAT from BXH/HXB recombinant inbred strains, derived from the SHR (spontaneously hypertensive rat) and BN (Brown Norway) progenitors, we identified Cd36 (fatty acid translocase) as the hub gene of co-expression module associated with BAT relative weight and function. An important aspect of BAT biology is to better understand the mechanisms regulating the uptake and utilization of fatty acids and glucose. Accordingly, BAT function in the SHR that harbors mutant nonfunctional Cd36 variant (hereafter referred to as SHR-Cd36⁻/⁻) was compared with SHR transgenic line expressing wild type Cd36 under control of a universal promoter (hereafter referred to as SHR-Cd36⁺/⁺). BAT was incubated in media containing insulin and 14C-U-glucose alone or 14C-U-glucose together with palmitate. Incorporation of glucose into BAT lipids was significantly higher in SHR-Cd36⁺/⁺ versus SHR-Cd36⁻/⁻ rats when incubation media contained glucose alone (SHR-Cd36⁻/⁻ 591 ± 75 vs. SHR-Cd36⁺/⁺ 1036 ± 135 nmol/gl./2h; P < 0.005). Adding palmitate into incubation media had no effect in SHR-Cd36⁻/⁻ rats but significantly reduced glucose incorporation into BAT lipids in SHR-Cd36⁺/⁺ (SHR-Cd36⁻/⁻ 543 ± 55 vs. SHR-Cd36⁺/⁺ 766 ± 75 nmol/gl./2h; P < 0.05 denotes significant Cd36 x palmitate interaction determined by two-way ANOVA). This Cd36-dependent reduced glucose uptake in SHR-Cd36⁺/⁺ BAT was likely secondary to increased palmitate incorporation and utilization due to the presence of wild type Cd36 fatty acid translocase in transgenic rats. This possibility is supported by increased incorporation of 14C-U-palmitate into BAT lipids in the presence of both palmitate and glucose in incubation media (palmitate alone: SHR-Cd36⁻/⁻ 870 ± 21 vs. SHR-Cd36⁺/⁺ 899 ± 42; glucose+palmitate: SHR-Cd36⁻/⁻ 899 ± 47 vs. SHR-Cd36⁺/⁺ 1460 ± 111 nmol/palm./2h; P < 0.05 denotes significant Cd36 x glucose interaction determined by two-way ANOVA). It is possible that addition of glucose into the incubation media increased palmitate incorporation into BAT lipids in SHR-Cd36⁺/⁺ rats because of glucose availability for glycerol phosphate production and increased triglyceride synthesis. These changes in glucose and palmitate incorporation into BAT lipids were associated with significant differential expression of Irs1, Irs2, Slc2a4 and Foxo1 genes involved in insulin signaling and glucose metabolism only in SHR-Cd36⁺/⁺ rats which suggests Cd36-dependent effects on insulin action. In conclusion, these results provide compelling evidence that Cd36 plays an important role in BAT insulin signaling and energy substrate utilization.

Keywords: brown adipose tissue, Cd36, energy substrate utilization, insulin signaling, spontaneously hypertensive rat

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168 The Use of Prestige Language in Tennessee Williams’s "A Streetcar Named Desire"

Authors: Stuart Noel

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In a streetcar Named Desire, Tennessee Williams presents Blanche DuBois, a most complex and intriguing character who often uses prestige language to project the image of an upper-class speaker and to disguise her darker and complicated self. She embodies various fascinating and contrasting characteristics. Like New Orleans (the locale of the play), Blanche represents two opposing images. One image projects that of genteel, Southern charm and beauty, speaking formally and using prestige language and what some linguists refer to as “hypercorrection,” and the other image reveals that of a soiled, deteriorating façade, full of decadence and illusion. Williams said on more than one occasion that Blanche’s use of such language was a direct reflection of her personality and character (as a high school English teacher). Prestige language is an exaggeratedly elevated, pretentious, and oftentimes melodramatic form of one’s language incorporating superstandard or more standard speech than usual in order to project a highly authoritative individual identity. Speech styles carry personal identification meaning not only because they are closely associated with certain social classes but because they tend to be associated with certain conversational contexts. Features which may be considered to be “elaborated” in form (for example, full forms vs. contractions) tend to cluster together in speech registers/styles which are typically considered to be more formal and/or of higher social prestige, such as academic lectures and news broadcasts. Members of higher social classes have access to the elaborated registers which characterize formal writings and pre-planned speech events, such as lectures, while members of lower classes are relegated to using the more economical registers associated with casual, face-to-face conversational interaction, since they do not participate in as many planned speech events as upper-class speakers. Tennessee Williams’s work is characteristically concerned with the conflict between the illusions of an individual and the reality of his/her situation equated with a conflict between truth and beauty. An examination of Blanche DuBois reveals a recurring theme of art and decay and the use of prestige language to reveal artistry in language and to hide a deteriorating self. His graceful and poetic writing personifies her downfall and deterioration. Her loneliness and disappointment are the things so often strongly feared by the sensitive artists and heroes in the world. Hers is also a special and delicate human spirit that is often misunderstood and repressed by society. Blanche is afflicted with a psychic illness growing out of her inability to face the harshness of human existence. She is a sensitive, artistic, and beauty-haunted creature who is avoiding her own humanity while hiding behind her use of prestige language. And she embodies a partial projection of Williams himself.

Keywords: American drama, prestige language, Southern American literature, Tennessee Williams

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167 Investigation on Single Nucleotide Polymorphism in Candidate Genes and Their Association with Occurrence of Mycobacterium avium Subspecies Paratuberculosis Infection in Cattle

Authors: Ran Vir Singh, Anuj Chauhan, Subhodh Kumar, Rajesh Rathore, Satish Kumar, B Gopi, Sushil Kumar, Tarun Kumar, Ramji Yadav, Donna Phangchopi, Shoor Vir Singh

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Paratuberculosis caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a chronic granulomatous enteritis affecting ruminants. It is responsible for significant economic losses in livestock industry worldwide. This organism is also of public health concern due to an unconfirmed link to Crohn’s disease. Susceptibility to paratuberculosis has been suggested to have genetic component with low to moderate heritability. Number of SNPs in various candidates genes have been observed to be affecting the susceptibility toward paratuberculosis. The objective of this study was to explore the association of various SNPs in the candidate genes and QTL region with MAP. A total of 117 SNPs from SLC11A1, IFNG, CARD15, TLR2, TLR4, CLEC7A, CD209, SP110, ANKARA2, PGLYRP1 and one QTL were selected for study. A total of 1222 cattle from various organized herds, gauhsalas and farmer herds were screened for MAP infection by Johnin intradermal skin test, AGID, serum ELISA, fecal microscopy, fecal culture and IS900 blood PCR. Based on the results of these tests, a case and control population of 200 and 183 respectively was established for study. A total of 117 SNPs from 10 candidate genes and one QTL were selected and validated/tested in our case and control population by PCR-RFLP technique. Data was analyzed using SAS 9.3 software. Statistical analysis revealed that, 107 out of 117 SNPs were not significantly associated with occurrence of MAP. Only SNP rs55617172 of TLR2, rs8193046 and rs8193060 of TLR4, rs110353594 and rs41654445 of CLEC7A, rs208814257of CD209, rs41933863 of ANKRA2, two loci {SLC11A1(53C/G)} and {IFNG (185 G/r) } and SNP rs41945014 in QTL region was significantly associated with MAP. Six SNP from 10 significant SNPs viz., rs110353594 and rs41654445 from CLEC7A, rs8193046 and rs8193060 from TLR4, rs109453173 from SLC11A1 rs208814257 from CD209 were validated in new case and control population. Out of these only one SNP rs8193046 of TLR4 gene was found significantly associated with occurrence of MAP in cattle. ODD ratio indicates that animals with AG genotype were more susceptible to MAP and this finding is in accordance with the earlier report. Hence it reaffirms that AG genotype can serve as a reliable genetic marker for indentifying more susceptible cattle in future selection against MAP infection in cattle.

Keywords: SNP, candidate genes, paratuberculosis, cattle

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166 DNA Hypomethylating Agents Induced Histone Acetylation Changes in Leukemia

Authors: Sridhar A. Malkaram, Tamer E. Fandy

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Purpose: 5-Azacytidine (5AC) and decitabine (DC) are DNA hypomethylating agents. We recently demonstrated that both drugs increase the enzymatic activity of the histone deacetylase enzyme SIRT6. Accordingly, we are comparing the changes H3K9 acetylation changes in the whole genome induced by both drugs using leukemia cells. Description of Methods & Materials: Mononuclear cells from the bone marrow of six de-identified naive acute myeloid leukemia (AML) patients were cultured with either 500 nM of DC or 5AC for 72 h followed by ChIP-Seq analysis using a ChIP-validated acetylated-H3K9 (H3K9ac) antibody. Chip-Seq libraries were prepared from treated and untreated cells using SMARTer ThruPLEX DNA- seq kit (Takara Bio, USA) according to the manufacturer’s instructions. Libraries were purified and size-selected with AMPure XP beads at 1:1 (v/v) ratio. All libraries were pooled prior to sequencing on an Illumina HiSeq 1500. The dual-indexed single-read Rapid Run was performed with 1x120 cycles at 5 pM final concentration of the library pool. Sequence reads with average Phred quality < 20, with length < 35bp, PCR duplicates, and those aligning to blacklisted regions of the genome were filtered out using Trim Galore v0.4.4 and cutadapt v1.18. Reads were aligned to the reference human genome (hg38) using Bowtie v2.3.4.1 in end-to-end alignment mode. H3K9ac enriched (peak) regions were identified using diffReps v1.55.4 software using input samples for background correction. The statistical significance of differential peak counts was assessed using a negative binomial test using all individuals as replicates. Data & Results: The data from the six patients showed significant (Padj<0.05) acetylation changes at 925 loci after 5AC treatment versus 182 loci after DC treatment. Both drugs induced H3K9 acetylation changes at different chromosomal regions, including promoters, coding exons, introns, and distal intergenic regions. Ten common genes showed H3K9 acetylation changes by both drugs. Approximately 84% of the genes showed an H3K9 acetylation decrease by 5AC versus 54% only by DC. Figures 1 and 2 show the heatmaps for the top 100 genes and the 99 genes showing H3K9 acetylation decrease after 5AC treatment and DC treatment, respectively. Conclusion: Despite the similarity in hypomethylating activity and chemical structure, the effect of both drugs on H3K9 acetylation change was significantly different. More changes in H3K9 acetylation were observed after 5 AC treatments compared to DC. The impact of these changes on gene expression and the clinical efficacy of these drugs requires further investigation.

Keywords: DNA methylation, leukemia, decitabine, 5-Azacytidine, epigenetics

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165 Lactobacillus rhamnosus GG Increases the Re-Epithelialization Rate of Model Wounds by Stimulating Keratinocyte Migration in Ex-Vivo

Authors: W. Mohammedsaeed, A. J. Mcbain, S. M. Cruickshank, C. A. O’Neill

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Many studies have demonstrated the importance of probiotics and their potential therapeutic effects within the gut. Recently, the possible therapeutic effects of probiotics in other tissues have also begun to be investigated. Comparatively few studies have evaluated the use of topical probiotics in relation to the skin. In this study, we have conducted preliminary investigations into whether a well-known probiotic, Lactobacillus rhamnosus GG (LGG), can increase the rate of re-epithelialization in a model wound. Full-thickness skin was obtained from individuals undergoing elective cosmetic surgery. This skin was wounded using excisional punch and cultured using a serum-free medium, either in the presence or absence of L. rhamnosus GG lysate. Histological staining of the sections was performed with Haematoxylin& Eosin E to quantify “epithelial tongue length”. This is the length of the new epithelial ‘tongue’ that grows and covers the exposed dermis at the inner wound edges. The length of the new epithelial ‘tongue’ was compared in untreated section and section treated with and L. rhamnosus GG made using108CFU/ml bacterial cells. L. rhamnosus GG lysate enhanced significantly the re-epithelialisation of treated wounds compared with that of untreated wounds (P=0.005, n=3). Tongue length, at day 1 was 7.55μm 0.15, at day 3 it was 18.5μm 0.25 and at day 7 was 22.9μm 0.35. These results can be compared with untreated cultures in which tongue length was 3.25μm 0.35, day 3 was 9.65μm 0.25 and day 7 was 13.5μm 0.15 post-wounding. In ex-vivo proliferation and migration cells were measured by determining the expression of nuclear proliferation marker Ki-67 and the expression of Phosphorylated cortactin respectively demonstrated that L. rhamnosus GG significantly increased NHEK proliferation and migration rates relative to controls. However, the dominant mechanism was migration because in ex-vivo skin treated with the L. rhamnosus GG up-regulated the gene expression of the chemokine receptor and ligands CXCR2 and CXCL2 comparing with controls (P=0.02, P=0.03 respectively, n=3). High levels of CXCL2/CXCL2 have already been implicated in multiple aspects of stimulation of wound healing through activation of keratinocyte migration. These data demonstrate that lysates from Lactobacillus rhamnosus GG increase re-epithelialization by stimulation of keratinocyte migration. The current study identifies the partial mechanism that contribute to stimulating the wound-healing process ex vivo in response to L. rhamnosus GG lysate is an increase in the production of CXCL2/ CXCR2 in ex vivo models. The use of probiotic lysates potentially offers new options to develop treatments that could improve wound healing.

Keywords: Lactobacillus rhamnosus GG, wounds, migration, lysate

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164 Toxic Chemicals from Industries into Pacific Biota. Investigation of Polychlorinated Biphenyls (PCBs), Dioxins (PCDD), Furans (PCDF) and Polybrominated Diphenyls (PBDE No. 47) in Tuna and Shellfish in Kiribati, Solomon Islands and the Fiji Islands

Authors: Waisea Votadroka, Bert Van Bavel

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The most commonly consumed shellfish species produced in the Pacific, shellfish and tuna fish, were investigated for the occurrence of a range of brominated and chlorinated contaminants in order to establish current levels. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were analysed in the muscle of tuna species Katsuwonis pelamis, yellow fin tuna, and shellfish species from the Fiji Islands. The investigation of polychlorinated biphenyls (PCBs), furans (PCDFs) and polybrominated diphenylethers (PBDE No.47) in tuna and shellfish in Kiribati, Solomon Islands and Fiji is necessary due to the lack of research data in the Pacific region. The health risks involved in the consumption of marine foods laced with toxic organo-chlorinated and brominated compounds makes in the analyses of these compounds in marine foods important particularly when Pacific communities rely on these resources as their main diet. The samples were homogenized in a motor with anhydrous sodium sulphate in the ratio of 1:3 (muscle) and 1:4-1:5 (roe and butter). The tuna and shellfish samples were homogenized and freeze dried at the sampling location at the Institute of Applied Science, Fiji. All samples were stored in amber glss jars at -18 ° C until extraction at Orebro University. PCDD/Fs, PCBs and pesticides were all analysed using an Autospec Ultina HRGC/HRMS operating at 10,000 resolutions with EI ionization at 35 eV. All the measurements were performed in the selective ion recording mode (SIR), monitoring the two most abundant ions of the molecular cluster (PCDD/Fs and PCBs). Results indicated that the Fiji Composite sample for Batissa violacea range 0.7-238.6 pg/g lipid; Fiji sample composite Anadara antiquate range 1.6 – 808.6 pg/g lipid; Solomon Islands Katsuwonis Pelamis 7.5-3770.7 pg/g lipid; Solomon Islands Yellow Fin tuna 2.1 -778.4 pg/g lipid; Kiribati Katsuwonis Pelamis 4.8-1410 pg/g lipids. The study has demonstrated that these species are good bio-indicators of the presence of these toxic organic pollutants in edible marine foods. Our results suggest that for pesticides levels, p,p-DDE is the most dominant for all the groups and seems to be highest at 565.48 pg/g lipid in composite Batissa violacea from Fiji. For PBDE no.47 in comparing all samples, the composite Batissa violacea from Fiji had the highest level of 118.20 pg/g lipid. Based upon this study, the contamination levels found in the study species were quite lower compared with levels reported in impacted ecosystems around the world

Keywords: polychlorinated biphenyl, polybrominated diphenylethers, pesticides, organoclorinated pesticides, PBDEs

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163 Oat βeta Glucan Attenuates the Development of Atherosclerosis and Improves the Intestinal Barrier Function by Reducing Bacterial Endotoxin Translocation in APOE-/- MICE

Authors: Dalal Alghawas, Jetty Lee, Kaisa Poutanen, Hani El-Nezami

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Oat β-glucan a water soluble non starch linear polysaccharide has been approved as a cholesterol lowering agent by various food safety administrations and is commonly used to reduce the risk of heart disease. The molecular weight of oat β-glucan can vary depending on the extraction and fractionation methods. It is not clear whether the molecular weight has a significant impact at reducing the acceleration of atherosclerosis. The aim of this study was to investigate three different oat β-glucan fractionations on the development of atherosclerosis in vivo. With special focus on plaque stability and the intestinal barrier function. To test this, ApoE-/- female mice were fed a high fat diet supplemented with oat bran, high molecular weight (HMW) oat β-glucan fractionate and low molecular weight (LMW) oat β-glucan fractionate for 16 weeks. Atherosclerosis risk markers were measured in the plasma, heart and aortic tree. Plaque size was measured in the aortic root and aortic tree. ICAM-1, VCAM-1, E-Selectin, P-Selectin, protein levels were assessed from the aortic tree to determine plaque stability at 16 weeks. The expression of p22phox at the aortic root was evaluated to study the NADPH oxidase complex involved in nitric oxide bioavailability and vascular elasticity. The tight junction proteins E-cadherin and beta-catenin from western blot analyses were analysed as an intestinal barrier function test. Plasma LPS, intestinal D-lactate levels and hepatic FMO gene expression were carried out to confirm whether the compromised intestinal barrier lead to endotoxemia. The oat bran and HMW oat β-glucan diet groups were more effective than the LMW β-glucan diet group at reducing the plaque size and showed marked improvements in plaque stability. The intestinal barrier was compromised for all the experimental groups however the endotoxemia levels were higher in the LMW β-glucan diet group. The oat bran and HMW oat β-glucan diet groups were more effective at attenuating the development of atherosclerosis. Reasons for this could be due to the LMW oat β-glucan diet group’s low viscosity in the gut and the inability to block the reabsorption of cholesterol. Furthermore the low viscosity may allow more bacterial endotoxin translocation through the impaired intestinal barrier. In future food technologists should carefully consider how to incorporate LMW oat β-glucan as a health promoting food.

Keywords: Atherosclerosis, beta glucan, endotoxemia, intestinal barrier function

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162 Motivational Profiles of the Entrepreneurial Career in Spanish Businessmen

Authors: Magdalena Suárez-Ortega, M. Fe. Sánchez-García

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This paper focuses on the analysis of the motivations that lead people to undertake and consolidate their business. It is addressed from the framework of planned behavior theory, which recognizes the importance of the social environment and cultural values, both in the decision to undertake business and in business consolidation. Similarly, it is also based on theories of career development, which emphasize the importance of career management competencies and their connections to other vital aspects of people, including their roles within their families and other personal activities. This connects directly with the impact of entrepreneurship on the career and the professional-personal project of each individual. This study is part of the project titled Career Design and Talent Management (Ministry of Economy and Competitiveness of Spain, State Plan 2013-2016 Excellence Ref. EDU2013-45704-P). The aim of the study is to identify and describe entrepreneurial competencies and motivational profiles in a sample of 248 Spanish entrepreneurs, considering the consolidated profile and the profile in transition (n = 248).In order to obtain the information, the Questionnaire of Motivation and conditioners of the entrepreneurial career (MCEC) has been applied. This consists of 67 items and includes four scales (E1-Conflicts in conciliation, E2-Satisfaction in the career path, E3-Motivations to undertake, E4-Guidance Needs). Cluster analysis (mixed method, combining k-means clustering with a hierarchical method) was carried out, characterizing the groups profiles according to the categorical variables (chi square, p = 0.05), and the quantitative variables (ANOVA). The results have allowed us to characterize three motivational profiles relevant to the motivation, the degree of conciliation between personal and professional life, and the degree of conflict in conciliation, levels of career satisfaction and orientation needs (in the entrepreneurial project and life-career). The first profile is formed by extrinsically motivated entrepreneurs, professionally satisfied and without conflict of vital roles. The second profile acts with intrinsic motivation and also associated with family models, and although it shows satisfaction with their professional career, it finds a high conflict in their family and professional life. The third is composed of entrepreneurs with high extrinsic motivation, professional dissatisfaction and at the same time, feel the conflict in their professional life by the effect of personal roles. Ultimately, the analysis has allowed us to line the kinds of entrepreneurs to different levels of motivation, satisfaction, needs and articulation in professional and personal life, showing characterizations associated with the use of time for leisure, and the care of the family. Associations related to gender, age, activity sector, environment (rural, urban, virtual), and the use of time for domestic tasks are not identified. The model obtained and its implications for the design of training actions and orientation to entrepreneurs is also discussed.

Keywords: motivation, entrepreneurial career, guidance needs, life-work balance, job satisfaction, assessment

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161 Structural and Binding Studies of Peptidyl-tRNA Hydrolase from Pseudomonas aeruginosa Provide a Platform for the Structure Based Inhibitor Design against Peptidyl-tRNA Hydrolase

Authors: Sujata Sharma, Avinash Singh, Lovely Gautam, Pradeep Sharma, Mau Sinha, Asha Bhushan, Punit Kaur, Tej P. Singh

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Peptidyl-tRNA hydrolase (Pth) Pth is an essential bacterial enzyme that catalyzes the release of free tRNA and peptide moeities from peptidyl tRNAs during stalling of protein synthesis. In order to design inhibitors of Pth from Pseudomonas aeruginosa (PaPth), we have determined the structures of PaPth in its native state and in the bound states with two compounds, amino acylate-tRNA analogue (AAtA) and 5-azacytidine (AZAC). The peptidyl-tRNA hydrolase gene from Pseudomonas aeruginosa was amplified by Phusion High-Fidelity DNA Polymerase using forward and reverse primers, respectively. The E. coliBL21 (λDE3) strain was used for expression of the recombinant peptidyl-tRNA hydrolase from Pseudomonas aeruginosa. The protein was purified using a Ni-NTA superflow column. The crystallization experiments were carried out using hanging drop vapour diffusion method. The crystals diffracted to 1.50 Å resolution. The data were processed using HKL-2000. The polypeptide chain of PaPth consists of 194 amino acid residues from Met1 to Ala194. The centrally located β-structure is surrounded by α-helices from all sides except the side that has entrance to the substrate binding site. The structures of the complexes of PaPth with AAtA and AZAC showed the ligands bound to PaPth in the substrate binding cleft and interacted with protein atoms extensively. The residues that formed intermolecular hydrogen bonds with the atoms of AAtA included Asn12, His22, Asn70, Gly113, Asn116, Ser148, and Glu161 of the symmetry related molecule. The amino acids that were involved in hydrogen bonded interactions in case of AZAC included, His22, Gly113, Asn116, and Ser148. As indicated by fittings of two ligands and the number of interactions made by them with protein atoms, AAtA appears to be a more compatible with the structure of the substrate binding cleft. However, there is a further scope to achieve a better stacking than that of O-tyrosyl moiety because it is not still ideally stacked. These observations about the interactions between the protein and ligands have provided the information about the mode of binding of ligands, nature and number of interactions. This information may be useful for the design of tight inhibitors of Pth enzymes.

Keywords: peptidyl tRNA hydrolase, Acinetobacter baumannii, Pth enzymes, O-tyrosyl

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160 Chloride Ion Channels Play a Role in Mediating Immune Response during Pseudomonas aeruginosa Infection

Authors: Hani M. Alothaid, Louise Robson, Richmond Muimo

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Cystic fibrosis (CF) is a disease that affects respiratory function and in EU it affects about 1 in 2,500 live births with an average 40-year life expectancy. This disease caused by mutations within the gene encoding the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) chloride channel leading to dysregulation of epithelial fluid transport and chronic lung inflammation, suggesting functional alterations of immune cells. In airways, CFTR been found to form a functional complex with S100A10 and AnxA2 in a cAMP/PKA dependent manner. The multiprotein complex of AnxA2-S100A10 and CFTR is also regulated by calcineurin. The aim of this study was i) to investigate whether chloride ion (Cl−) channels are activated by Pseudomonas aeruginosa lipopolysaccharide (LPS from PA), ii) if this activation is regulated by cAMP/PKA/calcineurin pathway and iii) to investigate the role of LPS-activated Cl− channels in the release of pro-inflammatory cytokines by immune cells. Human peripheral blood monocytes were used in the study. Whole-cell patch records showed that LPS from PA can activate Cl− channels, including CFTR and outwardly-rectifying Cl− channel (ORCC). This activation appears to require an intact PKA/calcineurin signalling pathway. The Gout in the presence of LPS was significantly inhibited by diisothiocyanatostilbene-disulfonic acid (DIDS), an ORCC blocker (p<0.001). The Gout was further suppressed by CFTR(inh)-172, a specific inhibitor for CFTR channels (p<0.001). Monocytes pre-incubated with PKA inhibitor or calcineurin inhibitor before stimulated with LPS from PA that were resulted in DIDS and CFTR(inh)-172 insensitive currents. Activation of both ORCC and CFTR was however, observed in response to monocytes exposure to LPS. Additionally, ELISA showed that the CFTR and ORCC play a role in mediating the release of pro-inflammatory cytokines such as IL-1β upon exposure of monocytes to LPS. However, this secretion was significantly inhibited due to CFTR and ORCC inhibition. However, Cl− may play a role in IL-1β release independent of cAMP/PKA/calcineurin signalling due to the enhancement of IL-1β secretion even when cAMP/PKA/calcineurin pathway was inhibited. In conclusion, our data confirmed that LPS from PA activates Cl− channels in human peripheral blood monocytes. Our data also confirmed that Cl− channels were involved in IL-1β release in monocytes upon exposure to LPS. However, it has been found that PKA and calcineurin does not seem to influence the Cl− dependent cytokine release.

Keywords: cystic fibrosis, CFTR, Annexin A2, S100A10, PP2B, PKA, outwardly-rectifying Cl− channel, Pseudomonas aeruginosa

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159 Bank Internal Controls and Credit Risk in Europe: A Quantitative Measurement Approach

Authors: Ellis Kofi Akwaa-Sekyi, Jordi Moreno Gené

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Managerial actions which negatively profile banks and impair corporate reputation are addressed through effective internal control systems. Disregard for acceptable standards and procedures for granting credit have affected bank loan portfolios and could be cited for the crises in some European countries. The study intends to determine the effectiveness of internal control systems, investigate whether perceived agency problems exist on the part of board members and to establish the relationship between internal controls and credit risk among listed banks in the European Union. Drawing theoretical support from the behavioural compliance and agency theories, about seventeen internal control variables (drawn from the revised COSO framework), bank-specific, country, stock market and macro-economic variables will be involved in the study. A purely quantitative approach will be employed to model internal control variables covering the control environment, risk management, control activities, information and communication and monitoring. Panel data from 2005-2014 on listed banks from 28 European Union countries will be used for the study. Hypotheses will be tested and the Generalized Least Squares (GLS) regression will be run to establish the relationship between dependent and independent variables. The Hausman test will be used to select whether random or fixed effect model will be used. It is expected that listed banks will have sound internal control systems but their effectiveness cannot be confirmed. A perceived agency problem on the part of the board of directors is expected to be confirmed. The study expects significant effect of internal controls on credit risk. The study will uncover another perspective of internal controls as not only an operational risk issue but credit risk too. Banks will be cautious that observing effective internal control systems is an ethical and socially responsible act since the collapse (crisis) of financial institutions as a result of excessive default is a major contagion. This study deviates from the usual primary data approach to measuring internal control variables and rather models internal control variables in a quantitative approach for the panel data. Thus a grey area in approaching the revised COSO framework for internal controls is opened for further research. Most bank failures and crises could be averted if effective internal control systems are religiously adhered to.

Keywords: agency theory, credit risk, internal controls, revised COSO framework

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158 Newly Designed Ecological Task to Assess Cognitive Map Reading Ability: Behavioral Neuro-Anatomic Correlates of Mental Navigation

Authors: Igor Faulmann, Arnaud Saj, Roland Maurer

Abstract:

Spatial cognition consists in a plethora of high level cognitive abilities: among them, the ability to learn and to navigate in large scale environments is probably one of the most complex skills. Navigation is thought to rely on the ability to read a cognitive map, defined as an allocentric representation of ones environment. Those representations are of course intimately related to the two geometrical primitives of the environment: distance and direction. Also, many recent studies point to a predominant hippocampal and para-hippocampal role in spatial cognition, as well as in the more specific cluster of navigational skills. In a previous study in humans, we used a newly validated test assessing cognitive map processing by evaluating the ability to judge relative distances and directions: the CMRT (Cognitive Map Recall Test). This study identified in topographically disorientated patients (1) behavioral differences between the evaluation of distances and of directions, and (2) distinct causality patterns assessed via VLSM (i.e., distinct cerebral lesions cause distinct response patterns depending on the modality (distance vs direction questions). Thus, we hypothesized that: (1) if the CMRT really taps into the same resources as real navigation, there would be hippocampal, parahippocampal, and parietal activation, and (2) there exists underlying neuroanatomical and functional differences between the processing of this two modalities. Aiming toward a better understanding of the neuroanatomical correlates of the CMRT in humans, and more generally toward a better understanding of how the brain processes the cognitive map, we adapted the CMRT as an fMRI procedure. 23 healthy subjects (11 women, 12 men), all living in Geneva for at least 2 years, underwent the CMRT in fMRI. Results show, for distance and direction taken together, than the most active brain regions are the parietal, frontal and cerebellar parts. Additionally, and as expected, patterns of brain activation differ when comparing the two modalities. Furthermore, distance processing seems to rely more on parietal regions (compared to other brain regions in the same modality and also to direction). It is interesting to notice that no significant activity was observed in the hippocampal or parahippocampal areas. Direction processing seems to tap more into frontal and cerebellar brain regions (compared to other brain regions in the same modality and also to distance). Significant hippocampal and parahippocampal activity has been shown only in this modality. This results demonstrated a complex interaction of structures which are compatible with response patterns observed in other navigational tasks, thus showing that the CMRT taps at least partially into the same brain resources as real navigation. Additionally, differences between the processing of distances and directions leads to the conclusion that the human brain processes each modality distinctly. Further research should focus on the dynamics of this processing, allowing a clearer understanding between the two sub-processes.

Keywords: cognitive map, navigation, fMRI, spatial cognition

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157 Using the Theory of Reasoned Action and Parental Mediation Theory to Examine Cyberbullying Perpetration among Children and Adolescents

Authors: Shirley S. Ho

Abstract:

The advancement and development of social media have inadvertently brought about a new form of bullying – cyberbullying – that transcends across physical boundaries of space. Although extensive research has been conducted in the field of cyberbullying, most of these studies have taken an overwhelmingly empirical angle. Theories guiding cyberbullying research are few. Furthermore, very few studies have explored the association between parental mediation and cyberbullying, with majority of existing studies focusing on cyberbullying victimization rather than perpetration. Therefore, this present study investigates cyberbullying perpetration from a theoretical angle, with a focus on the Theory of Reasoned Action and the Parental Mediation Theory. More specifically, this study examines the direct effects of attitude, subjective norms, descriptive norms, injunctive norms and active mediation and restrictive mediation on cyberbullying perpetration on social media among children and adolescents in Singapore. Furthermore, the moderating role of age on the relationship between parental mediation and cyberbullying perpetration on social media are examined. A self-administered paper-and-pencil nationally-representative survey was conducted. Multi-stage cluster random sampling was used to ensure that schools from all the four (North, South, East, and West) regions of Singapore were equally represented in the sample used for the survey. In all 607 upper primary school children (i.e., Primary 4 to 6 students) and 782 secondary school adolescents participated in our survey. The total average response rates were 69.6% for student participation. An ordinary least squares hierarchical regression analysis was conducted to test the hypotheses and research questions. The results revealed that attitude and subjective norms were positively associated with cyberbullying perpetration on social media. Descriptive norms and injunctive norms were not found to be significantly associated with cyberbullying perpetration. The results also showed that both parental mediation strategies were negatively associated with cyberbullying perpetration on social media. Age was a significant moderator of both parental mediation strategies and cyberbullying perpetration. The negative relationship between active mediation and cyberbullying perpetration was found to be greater in the case of children than adolescents. Children who received high restrictive parental mediation were less likely to perform cyberbullying behaviors, while adolescents who received high restrictive parental mediation were more likely to be engaged in cyberbullying perpetration. The study reveals that parents should apply active mediation and restrictive mediation in different ways for children and adolescents when trying to prevent cyberbullying perpetration. The effectiveness of active parental mediation for reducing cyberbullying perpetration was more in the case of children than for adolescents. Younger children were found to be more likely to respond more positively toward restrictive parental mediation strategies, but in the case of adolescents, overly restrictive control was found to increase cyberbullying perpetration. Adolescents exhibited less cyberbullying behaviors when under low restrictive strategies. Findings highlight that the Theory of Reasoned Action and Parental Mediation Theory are promising frameworks to apply in the examination of cyberbullying perpetration. The findings that different parental mediation strategies had differing effectiveness, based on the children’s age, bring about several practical implications that may benefit educators and parents when addressing their children’s online risk.

Keywords: cyberbullying perpetration, theory of reasoned action, parental mediation, social media, Singapore

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156 Molecular Detection of E. coli in Treated Wastewater and Well Water Samples Collected from Al Riyadh Governorate, Saudi Arabia

Authors: Hanouf A. S. Al Nuwaysir, Nadine Moubayed, Abir Ben Bacha, Islem Abid

Abstract:

Consumption of waste water continues to cause significant problems for human health in both developed and developing countries. Many regulations have been implied by different world authorities controlling water quality for the presence of coliforms used as standard indicators of water quality deterioration and historically leading health protection concept. In this study, the European directive for the detection of Escherichia coli, ISO 9308-1, was applied to examine and monitor coliforms in water samples collected from Wadi Hanifa and neighboring wells, Riyadh governorate, kingdom of Saudi Arabia, which is used for irrigation and industrial purposes. Samples were taken from different locations for 8 months consecutively, chlorine concentration ranging from 0.1- 0.4 mg/l, was determined using the DPD FREE CHLORINE HACH kit. Water samples were then analyzed following the ISO protocol which relies on the membrane filtration technique (0.45µm, pore size membrane filter) and a chromogenic medium TTC, a lactose based medium used for the detection and enumeration of total coliforms and E.coli. Data showed that the number of bacterial isolates ranged from 60 to 300 colonies/100ml for well and surface water samples respectively; where higher numbers were attributed to the surface samples. Organisms which apparently ferment lactose on TTC agar plates, appearing as orange colonies, were selected and additionally cultured on EMB and MacConkey agar for a further differentiation among E.coli and coliform bacteria. Two additional biochemical tests (Cytochrome oxidase and indole from tryptophan) were also investigated to detect and differentiate the presence of E.coli from other coliforms, E. coli was identified in an average of 5 to 7colonies among 25 selected colonies.On the other hand, a more rapid, specific and sensitive analytical molecular detection namely single colony PCR was also performed targeting hha gene to sensitively detect E.coli, giving more accurate and time consuming identification of colonies considered presumptively as E.coli. Comparative methodologies, such as ultrafiltration and direct DNA extraction from membrane filters (MoBio, Grermany) were also applied; however, results were not as accurate as the membrane filtration, making it a technique of choice for the detection and enumeration of water coliforms, followed by sufficiently specific enzymatic confirmatory stage.

Keywords: coliform, cytochrome oxidase, hha primer, membrane filtration, single colony PCR

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155 Application of Thermoplastic Microbioreactor to the Single Cell Study of Budding Yeast to Decipher the Effect of 5-Hydroxymethylfurfural on Growth

Authors: Elif Gencturk, Ekin Yurdakul, Ahmet Y. Celik, Senol Mutlu, Kutlu O. Ulgen

Abstract:

Yeast cells are generally used as a model system of eukaryotes due to their complex genetic structure, rapid growth ability in optimum conditions, easy replication and well-defined genetic system properties. Thus, yeast cells increased the knowledge of the principal pathways in humans. During fermentation, carbohydrates (hexoses and pentoses) degrade into some toxic by-products such as 5-hydroxymethylfurfural (5-HMF or HMF) and furfural. HMF influences the ethanol yield, and ethanol productivity; it interferes with microbial growth and is considered as a potent inhibitor of bioethanol production. In this study, yeast single cell behavior under HMF application was monitored by using a continuous flow single phase microfluidic platform. Microfluidic device in operation is fabricated by hot embossing and thermo-compression techniques from cyclo-olefin polymer (COP). COP is biocompatible, transparent and rigid material and it is suitable for observing fluorescence of cells considering its low auto-fluorescence characteristic. The response of yeast cells was recorded through Red Fluorescent Protein (RFP) tagged Nop56 gene product, which is an essential evolutionary-conserved nucleolar protein, and also a member of the box C/D snoRNP complexes. With the application of HMF, yeast cell proliferation continued but HMF slowed down the cell growth, and after HMF treatment the cell proliferation stopped. By the addition of fresh nutrient medium, the yeast cells recovered after 6 hours of HMF exposure. Thus, HMF application suppresses normal functioning of cell cycle but it does not cause cells to die. The monitoring of Nop56 expression phases of the individual cells shed light on the protein and ribosome synthesis cycles along with their link to growth. Further computational study revealed that the mechanisms underlying the inhibitory or inductive effects of HMF on growth are enriched in functional categories of protein degradation, protein processing, DNA repair and multidrug resistance. The present microfluidic device can successfully be used for studying the effects of inhibitory agents on growth by single cell tracking, thus capturing cell to cell variations. By metabolic engineering techniques, engineered strains can be developed, and the metabolic network of the microorganism can thus be manipulated such that chemical overproduction of target metabolite is achieved along with the maximum growth/biomass yield.  

Keywords: COP, HMF, ribosome biogenesis, thermoplastic microbioreactor, yeast

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154 Study of COVID-19 Intensity Correlated with Specific Biomarkers and Environmental Factors

Authors: Satendra Pal Singh, Dalip Kr. Kakru, Jyoti Mishra, Rajesh Thakur, Tarana Sarwat

Abstract:

COVID-19 is still an intrigue as far as morbidity or mortality is concerned. The rate of recovery varies from person to person, & it depends upon the accessibility of the healthcare system and the roles played by the physicians and caregivers. It is envisaged that with the passage of time, people would become immune to this virus, and those who are vulnerable would sustain themselves with the help of vaccines. The proposed study deals with the severeness of COVID-19 is associated with some specific biomarkers linked to correlate age and gender. We will be assessing the overall homeostasis of the persons who were affected by the coronavirus infection and also of those who recovered from it. Some people show more severe effects, while others show very mild symptoms, however, they show low CT values. Thus far, it is unclear why the new strain of Covid has different effects on different people in terms of age, gender, and ABO blood typing. According to data, the fatality rate with heart disease was 10.5 percent, 7.3 percent were diabetic, and 6 percent who are already infected from other comorbidities. However, some COVID-19 cases are worse than others & it is not fully explainable as of date. Overall data show that the ABO blood group is effective or prone to the risk of SARS-COV2 infection, while another study also shows the phenotypic effects of the blood group related to covid. It is an accepted fact that females have more strong immune systems than males, which may be related to the fact that females have two ‘X’ chromosomes, which might contain a more effective immunity booster gene on the X chromosome, and are capable to protect the female. Also specific sex hormones also induce a better immune response in a specific gender. This calls for in-depth analysis to be able to gain insight into this dilemma. COVID-19 is still not fully characterized, and thus we are not very familiar with its biology, mode of infection, susceptibility, and overall viral load in the human body. How many virus particles are needed to infect a person? How, then, comorbidity contribute to coronavirus infection? Since the emergence of this virus in 2020, a large number of papers have been published, and seemingly, vaccines have been prepared. But still, a large number of questions remain unanswered. The proneness of humans for infection by covid-19 needs to be established to be able to develop a better strategy to fight this virus. Our study will be on the Impact of demography on the Severity of covid-19 infection & at the same time, will look into gender-specific sensitivity of Covid-19 and the Operational variation of different biochemical markers in Covid-19 positive patients. Besides, we will be studying the co-relation, if any, of COVID severity & ABO Blood group type and the occurrence of the most common blood group type amongst positive patience.

Keywords: coronavirus, ABO blood group, age, gender

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153 Association of Genetically Proxied Cholesterol-Lowering Drug Targets and Head and Neck Cancer Survival: A Mendelian Randomization Analysis

Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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