Search results for: spatial gene
1036 MicroRNA in Bovine Corpus Luteum during Early Pregnancy
Authors: Rreze Gecaj, Corina Schanzenbach, Benedikt Kirchner, Michael Pfaffl, Bajram Berisha
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The maintenance of corpus lutem (CL) during early pregnancy in cattle is a critical and multifarious process. A luteotrophic mechanism originating from the embryo is widely accepted as the triggering signal for the CL maintenance. In the cattle, it is the interferon-tau (IFNT) secretion form conceptus that prevents CL regression and ensures progesterone production for the establishment of pregnancy. In addition to endocrine and paracrine signals, microRNA (miRNA) can also support CL sustainability during early pregnancy. MiRNA are small non-coding nucleic acids that regulate gene expression post-transcriptionally and are shown to be involved in the modulation of CL function. However, the examination of miRNAs in corpus luteum function at the early pregnancy still remains largely uncovered. This study aims at profiling the expression of miRNA in CL during the early pregnancy in cattle by comparing it with the CL form late cycle and with the regressed CL. Corpora lutea were assigned in two different groups during the cycle (C13 group, late CL: days 13-18 and C18, regressed CL group: day >18) and during the early pregnancy (group P: 1-2 month). The estrous cycle was determined by macroscopic examination and to age the fetus crown-rump length measurement was applied. A total of 9 corpora lutea from individual animals were included in the study, three corpora lutea for each group. MiRNAs population was profiled using small RNA next-generation sequencing and biologically significant miRNAs were evaluated for their differential expression using the DESeq2-methodology. We show that 6 differentially expressed miRNAs (bta-mir-2890, -2332, -2441-3p, -148b, -1248 and -29c) are common to both comparisons, P vs C13 and P vs C18. While for each stage individually we have identified unique miRNAs differentially expressed only for the given comparison. bta-miR-23a and -769 were unique miRNAs differentially expressed in P vs C13, whereas forty-four unique miRNAs were identified as differentially expressed in P vs C18. These data confirm that miRNAs are highly abundant in luteal tissue during early pregnancy and potentially regulate the CL maintenance at this stage of fetus development.Keywords: bovine, corpus luteum, microRNA, pregnancy, RNA-Seq
Procedia PDF Downloads 2591035 Large Eddy Simulation with Energy-Conserving Schemes: Understanding Wind Farm Aerodynamics
Authors: Dhruv Mehta, Alexander van Zuijlen, Hester Bijl
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Large Eddy Simulation (LES) numerically resolves the large energy-containing eddies of a turbulent flow, while modelling the small dissipative eddies. On a wind farm, these large scales carry the energy wind turbines extracts and are also responsible for transporting the turbines’ wakes, which may interact with downstream turbines and certainly with the atmospheric boundary layer (ABL). In this situation, it is important to conserve the energy that these wake’s carry and which could be altered artificially through numerical dissipation brought about by the schemes used for the spatial discretisation and temporal integration. Numerical dissipation has been reported to cause the premature recovery of turbine wakes, leading to an over prediction in the power produced by wind farms.An energy-conserving scheme is free from numerical dissipation and ensures that the energy of the wakes is increased or decreased only by the action of molecular viscosity or the action of wind turbines (body forces). The aim is to create an LES package with energy-conserving schemes to simulate wind turbine wakes correctly to gain insight into power-production, wake meandering etc. Such knowledge will be useful in designing more efficient wind farms with minimal wake interaction, which if unchecked could lead to major losses in energy production per unit area of the wind farm. For their research, the authors intend to use the Energy-Conserving Navier-Stokes code developed by the Energy Research Centre of the Netherlands.Keywords: energy-conserving schemes, modelling turbulence, Large Eddy Simulation, atmospheric boundary layer
Procedia PDF Downloads 4651034 Effect of Mistranslating tRNA Alanine on Polyglutamine Aggregation
Authors: Sunidhi Syal, Rasangi Tennakoon, Patrick O'Donoghue
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Polyglutamine (polyQ) diseases are a group of diseases related to neurodegeneration caused by repeats of the amino acid glutamine (Q) in the DNA, which translates into an elongated polyQ tract in the protein. The pathological explanation is that the polyQ tract forms cytotoxic aggregates in the neurons, leading to their degeneration. There are no cures or preventative efforts established for these diseases as of today, although the symptoms of these diseases can be relieved. This study specifically focuses on Huntington's disease, which is a type of polyQ disease in which aggregation is caused by the extended cytosine, adenine, guanine (CUG) codon repeats in the huntingtin (HTT) gene, which encodes for the huntingtin protein. Using this principle, we attempted to create six models, which included mutating wildtype tRNA alanine variant tRNA-AGC-8-1 to have glutamine anticodons CUG and UUG so serine is incorporated at glutamine sites in poly Q tracts. In the process, we were successful in obtaining tAla-8-1 CUG mutant clones in the HTTexon1 plasmids with a polyQ tract of 23Q (non-pathogenic model) and 74Q (disease model). These plasmids were transfected into mouse neuroblastoma cells to characterize protein synthesis and aggregation in normal and mistranslating cells and to investigate the effects of glutamines replaced with alanines on the disease phenotype. Notably, we observed no noteworthy differences in mean fluorescence between the CUG mutants for 23Q or 74Q; however, the Triton X-100 assay revealed a significant reduction in insoluble 74Q aggregates. We were unable to create a tAla-8-1 UUG mutant clone, and determining the difference in the effects of the two glutamine anticodons may enrich our understanding of the disease phenotype. In conclusion, by generating structural disruption with the amino acid alanine, it may be possible to find ways to minimize the toxicity of Huntington's disease caused by these polyQ aggregates. Further research is needed to advance knowledge in this field by identifying the cellular and biochemical impact of specific tRNA variants found naturally in human genomes.Keywords: Huntington's disease, polyQ, tRNA, anticodon, clone, overlap PCR
Procedia PDF Downloads 411033 Hepatocyte-Intrinsic NF-κB Signaling Is Essential to Control a Systemic Viral Infection
Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder
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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance
Procedia PDF Downloads 1911032 Recyclable Household Solid Waste Generation and Collection in Beijing, China
Authors: Tingting Liu, Yufeng Wu, Xi Tian, Yu Gong, Tieyong Zuo
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The household solid waste generated by household in Beijing is increasing quickly due to rapid population growth and lifestyle changes. However, there are no rigorous data on the generation and collection of the recyclable household solid wastes. The Beijing city government needs this information to make appropriate policies and plans for waste management. To address this information need, we undertook the first comprehensive study of recyclable household solid waste for Beijing. We carried out a survey of 500 families across sixteen districts in Beijing. We also analyzed the quantities, spatial distribution and categories of collected waste handled by curbside recyclers and permanent recycling centers for 340 of the 9797 city-defined residential areas of Beijing. From our results, we estimate that the total quantity of recyclable household solid waste was 1.8 million tonnes generated by Beijing household in 2013 and 71.6% of that was collected. The main generation categories were waste paper (24.4%), waste glass bottle (23.7%) and waste furniture (14.3%). The recycling rate was varied among different kinds of municipal solid waste. Also based on our study, we estimate there were 22.8 thousand curbside recyclers and 5.7 thousand permanent recycling centers in Beijing. The problems of household solid waste collecting system were inadequacies of authorized collection centers, skewed ratios of curbside recyclers and authorized permanent recycling centers, weak recycling awareness of residents and lack of recycling resources statistics and appraisal system. According to the existing problems, we put forward the suggestions to improve household solid waste management.Keywords: Municipal waste; Recyclable waste; Waste categories; Waste collection
Procedia PDF Downloads 2961031 The Effect of a 12 Week Rhythmic Movement Intervention on Selected Biomotor Abilities on Academy Rugby Players
Authors: Jocelyn Solomons, Kraak
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Rhythmic movement, also referred to as “dance”, involves the execution of different motor skills as well as the integration and sequencing of actions between limbs, timing and spatial precision. The aim of this study was therefore to investigate and compare the effect of a 16-week rhythmic movement intervention on flexibility, dynamic balance, agility, power and local muscular endurance of academy rugby players in the Western Cape, according to positional groups. Players (N ¼ 54) (age 18.66 0.81 years; height 1.76 0.69 cm; weight 76.77 10.69 kg), were randomly divided into a treatment-control [TCA] (n ¼ 28) and a control-treatment [CTB] (n ¼ 26) group. In this crossover experimental design, the interaction effect of the treatment order and the treatment time between the TCA and CTB group, was determined. Results indicated a statistically significant improvement (p < 0.05) in agility2 (p ¼ 0.06), power2 (p ¼ 0.05), local muscular endurance1 (p ¼ 0.01) & 3 (p ¼ 0.01) and dynamic balance (p < 0.01). Likewise, forwards and backs also showed statistically significant improvements (p < 0.05) per positional groups. Therefore, a rhythmic movement intervention has the potential to improve rugby-specific bio-motor skills and furthermore, improve positional specific skills should it be designed with positional groups in mind. Future studies should investigate, not only the effect of rhythmic movement on improving specific rugby bio-motor skills, but the potential of its application as an alternative training method during off- season (or detraining phases) or as a recovery method.Keywords: agility, dance, dynamic balance, flexibility, local muscular endurance, power, training
Procedia PDF Downloads 621030 The Comparison Study of Human Microbiome in Chronic Rhinosinusitis between Adults and Children
Authors: Il Ho Park, Joong Seob Lee, Sung Hun Kang, Jae-Min Shin, Il Seok Park, Seok Min Hong, Seok Jin Hong
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Introduction: The human microbiota is the aggregate of microorganisms, and the bacterial microbiome of the human digestive tract contributes to both health and disease. In health, bacteria are key components in the development of mucosal barrier function and in innate and adaptive immune responses, and they also work to suppress the establishment of pathogens. In human upper airway, the sinonasal microbiota might play an important role in chronic rhinosinusitis (CRS). The purpose of this study is to investigate the human upper airway microbiome in CRS patients and to compare the sinonasal microbiome of adults with children. Materials and methods: A total of 19 samples from 19 patients (Group1; 9 CRS in children, aged 5 to 14 years versus Group 2; 10 CRS in adults aged 21 to 59 years) were examined. Swabs were collected from the middle meatus and/or anterior ethmoid region under general anesthesia during endoscopic sinus surgery or tonsillectomy. After DNA extraction from swab samples, we analysed bacterial microbiome consortia using 16s rRNA gene sequencing approach (the Illumina MiSeq platform). Results: In this study, relatively abundance of the six bacterial phyla and tremendous genus and species found in substantial amounts in the individual sinus swab samples, include Corynebacterium, Hemophilus, Moraxella, and Streptococcus species. Anaerobes like Fusobacterium and Bacteroides were abundantly present in the children group, Bacteroides and Propionibacterium were present in adults group. In genus, Haemophilus was the most common CRS microbiome in children and Corynebacterium was the most common CRS microbiome in adults. Conclusions: Our results show the diversity of human upper airway microbiome, and the findings will suggest that CRS is a polymicrobial infection. The Corynebacterium and Hemophilus may live as commensals on mucosal surfaces of sinus in the upper respiratory tract. The further study will be needed for analysis of microbiome-human interactions in upper airway and CRS.Keywords: microbiome, upper airway, chronic rhinosinusitis, adult and children
Procedia PDF Downloads 1261029 Seawater Intrusion in the Coastal Aquifer of Wadi Nador (Algeria)
Authors: Abdelkader Hachemi & Boualem Remini
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Seawater intrusion is a significant challenge faced by coastal aquifers in the Mediterranean basin. This study aims to determine the position of the sharp interface between seawater and freshwater in the aquifer of Wadi Nador, located in the Wilaya of Tipaza, Algeria. A numerical areal sharp interface model using the finite element method is developed to investigate the spatial and temporal behavior of seawater intrusion. The aquifer is assumed to be homogeneous and isotropic. The simulation results are compared with geophysical prospection data obtained through electrical methods in 2011 to validate the model. The simulation results demonstrate a good agreement with the geophysical prospection data, confirming the accuracy of the sharp interface model. The position of the sharp interface in the aquifer is found to be approximately 1617 meters from the sea. Two scenarios are proposed to predict the interface position for the year 2024: one without pumping and the other with pumping. The results indicate a noticeable retreat of the sharp interface position in the first scenario, while a slight decline is observed in the second scenario. The findings of this study provide valuable insights into the dynamics of seawater intrusion in the Wadi Nador aquifer. The predicted changes in the sharp interface position highlight the potential impact of pumping activities on the aquifer's vulnerability to seawater intrusion. This study emphasizes the importance of implementing measures to manage and mitigate seawater intrusion in coastal aquifers. The sharp interface model developed in this research can serve as a valuable tool for assessing and monitoring the vulnerability of aquifers to seawater intrusion.Keywords: seawater, intrusion, sharp interface, Algeria
Procedia PDF Downloads 741028 Gold, Power, Protest, Examining How Digital Media and PGIS are Used to Protest the Mining Industry in Colombia
Authors: Doug Specht
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This research project sought to explore the links between digital media, PGIS and social movement organisations in Tolima, Colombia. The primary aim of the research was to examine how knowledge is created and disseminated through digital media and GIS in the region, and whether there exists the infrastructure to allow for this. The second strand was to ascertain if this has had a significant impact on the way grassroots movements work and produce collective actions. The third element is a hypothesis about how digital media and PGIS could play a larger role in activist activities, particularly in reference to the extractive industries. Three theoretical strands have been brought together to provide a basis for this research, namely (a) the politics of knowledge, (b) spatial management and inclusion, and (c) digital media and political engagement. Quantitative data relating to digital media and mobile internet use was collated alongside qualitative data relating to the likelihood of using digital media in activist campaigns, with particular attention being given to grassroots movements working against extractive industries in the Tolima region of Colombia. Through interviews, surveys and GIS analysis it has been possible to build a picture of online activism and the role of PPGIS within protest movement in the region of Tolima, Colombia. Results show a gap between the desires of social movements to use digital media and the skills and finances required to implement programs that utilise it. Maps and GIS are generally reserved for legal cases rather than for informing the lay person. However, it became apparent that the combination of digital/social media and PPGIS could play a significant role in supporting the work of grassroots movements.Keywords: PGIS, GIS, social media, digital media, mining, colombia, social movements, protest
Procedia PDF Downloads 4271027 In Silico Study of Cell Surface Structures of Parabacteroides distasonis Involved in Its Maintain Within the Gut Microbiota and Its Potential Pathogenicity
Authors: Jordan Chamarande, Lisiane Cunat, Corentine Alauzet, Catherine Cailliez-Grimal
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Gut microbiota (GM) is now considered a new organ mainly due to the microorganism’s specific biochemical interaction with its host. Although mechanisms underlying host-microbiota interactions are not fully described, it is now well-defined that cell surface molecules and structures of the GM play a key role in such relation. The study of surface structures of GM members is also fundamental for their role in the establishment of species in the versatile and competitive environment of the digestive tract and as a potential virulence factor. Among these structures are capsular polysaccharides (CPS), fimbriae, pili and lipopolysaccharides (LPS), all well-described for their central role in microorganism colonization and communication with host epithelium. The health-promoting Parabacteroides distasonis, which is part of the core microbiome, has recently received a lot of attention, showing beneficial properties for its host and as a new potential biotherapeutic product. However, to the best of the authors’ knowledge, the cell surface molecules and structures of P. distasonis that allow its maintain within the GM are not identified. Moreover, although P. distasonis is strongly recognized as intestinal commensal species with benefits for its host, it has also been recognized as an opportunistic pathogen. In this study, we reported gene clusters potentially involved in the synthesis of the capsule, fimbriae-like and pili-like cell surface structures in 26 P. distasonis genomes and applied the new RfbA-Typing classification in order to better understand and characterize the beneficial/pathogenic behaviour related to P. distasonis strains. In context, 2 different types of fimbriae, 3 of pilus and up to 14 capsular polysaccharide loci, have been identified over the 26 genomes studied. Moreover, the addition of data to the rfbA-Type classification modified the outcome by rearranging rfbA genes and adding a fifth group to the classification. In conclusion, the strain variability in terms of external proteinaceous structure could explain the inter-strain differences previously observed in P. distasonis adhesion capacities and its potential pathogenicity.Keywords: gut microbiota, Parabacteroides distasonis, capsular polysaccharide, fimbriae, pilus, O-antigen, pathogenicity, probiotic, comparative genomics
Procedia PDF Downloads 1031026 Study of Influencing Factors of Shrinking Cities Based on Factor Analysis: The Example of Halle Germany
Authors: Fang Yao, Minglei Chen
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City shrinkage is one of the thorny problems that many European cities have to face with nowadays. It is mainly expressed as the decrease of population in these cities. Eastern Germany is one of the pioneers of European shrinking cities with long shrinking history. Selecting one representative shrinking city Halle(Saale) in eastern Germany as research objective, collecting and investigating nearly 20 years (1993-2010) municipal data after the reunification of Germany. These data based on five dimensions, which are demographic, economic, social, spatial and environmental and total 16 eligible variables. Using Factor Analysis to dealing with these variables in order to assess the most important factors affecting shrinking Halle. The Factor Analysis shows that there are three main factors determine the shrinkage of Halle, namely demographical and economical factor, social stability factor, and city vitality factor. Three factors acts at different period of Halle’s shrinkage: from 1993 to 1997 the demographical and economical factor played an important role; from 1997 to 2004 the social stability is significant to city shrinkage; since 2005 city vitality factors determines the shrinkage of Halle. In recent years, the shrinkage in Halle mitigates that shows the sign of growing population. Thus the city Halle should focus on attaching more importance on the city vitality factor to prevent the city from shrinkage. Meanwhile, the city should possess a positive perspective that to shift the growth-oriented development to tap the potential of shrinking cities. This method is expected to apply to further research and other shrinking cities.Keywords: demography, factor analysis, Halle, shrinking cities
Procedia PDF Downloads 4141025 Towards a Methodology for the Assessment of Neighbourhood Design for Happiness
Authors: Tina Pujara
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Urban and regional research in the new emerging inter-disciplinary field of happiness is seemingly limited. However, it is progressively being recognized that there is enormous potential for social and behavioral scientists to add a spatial dimension to it. In fact, the happiness of communities can be notably influenced by the design and maintenance of the neighborhoods they inhabit. The probable key reasons being that places can facilitate human social connections and relationships. While it is increasingly being acknowledged that some neighborhood designs appear better suited for social connectedness than others, the plausible reasons for places to deter these characteristics and perhaps their influence on happiness are outwardly unknown. In addition, an explicit step wise methodology to assess neighborhood designs for happiness (of their communities) is not known to exist. This paper is an attempt towards developing such a methodological framework. The paper presents the development of a methodological framework for assessing neighborhood designs for happiness, with a particular focus on the outdoor shared spaces in neighborhoods. The developed methodological framework of investigation follows a mixed method approach and draws upon four different sources of information. The framework proposes an empirical examination of the contribution of neighborhood factors, particularly outdoor shared spaces, to individual happiness. One of the main tools proposed for this empirical examination is Jan Gehl’s Public Space Public Life (PSPL) Survey. The developed framework, as presented in the paper, is a contribution towards the development of a consolidated methodology for assessing neighborhood designs for happiness, which can further serve as a unique tool to inform urban designers, architects and other decision makers.Keywords: happiness, methodology, neighbourhood design, outdoor shared spaces
Procedia PDF Downloads 1631024 Poverty and Environmental Degeneration in Central City of Ibadan, Nigeria
Authors: Funmilayo Lanrewaju Amao, Amos Olusegun Amao, Odetoye Adeola Sunday, Joseph Joshua Olu
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There is a high magnitude of housing inadequacy in urban centers in Nigeria. This is manifested in quantitative and qualitative terms. Severe overcrowding and insanitary physical environment characterize the housing in the urban centers. The culminating effect of this is the growth of slum areas. This paper takes a critical look at inter-allia history and anatomy, general characteristic, present condition, root causes, official responses and reactions, possible solution and advocacy housing in central city slum of Ibadan. It also examines slum development and consequent deviant behaviors in the inner-city neighborhoods of Ibadan, the capital city of Oyo State, Nigeria. Residing there are many underemployed and unemployed individuals, these are miscreants who are generally socially frustrated. The activities of this group of people are a cause of concern. Deleterious and anti-social behaviors such as prostitution and house burglary are commonplace in the neighborhoods. The paper examines building conditions in the neighborhoods and the nexus with the deviant behavior of the inhabitants. The paper affirms that there is monumental deficiency in housing quality, while the design and the arrangement of the buildings into spatial units significantly influence the behavior of the residents. The paper suggests a two-prong approach in dealing with the situation. This involves urban renewal and slum upgrading programmes on the one hand, and an improvement in the socio-economic circumstances of the inhabitants, especially an increase in employment opportunity on the other.Keywords: slum, behavior, housing, poverty, environmental degeneration
Procedia PDF Downloads 4041023 Combining Laser Scanning and High Dynamic Range Photography for the Presentation of Bloodstain Pattern Evidence
Authors: Patrick Ho
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Bloodstain Pattern Analysis (BPA) forensic evidence can be complex, requiring effective courtroom presentation to ensure clear and comprehensive understanding of the analyst’s findings. BPA witness statements can often involve reference to spatial information (such as location of rooms, objects, walls) which, when coupled with classified blood patterns, may illustrate the reconstructed movements of suspects and injured parties. However, it may be difficult to communicate this information through photography alone, despite this remaining the UK’s established method for presenting BPA evidence. Through an academic-police partnership between the University of Warwick and West Midlands Police (WMP), an integrated 3D scanning and HDR photography workflow for BPA was developed. Homicide scenes were laser scanned and, after processing, the 3D models were utilised in the BPA peer-review process. The same 3D models were made available for court but were not always utilised. This workflow has improved the ease of presentation for analysts and provided 3D scene models that assist with the investigation. However, the effects of incorporating 3D scene models in judicial processes may need to be studied before they are adopted more widely. 3D models from a simulated crime scene and West Midlands Police cases approved for conference disclosure are presented. We describe how the workflow was developed and integrated into established practices at WMP, including peer-review processes and witness statement delivery in court, and explain the impact the work has had on the Criminal Justice System in the West Midlands.Keywords: bloodstain pattern analysis, forensic science, criminal justice, 3D scanning
Procedia PDF Downloads 961022 Extracting Terrain Points from Airborne Laser Scanning Data in Densely Forested Areas
Authors: Ziad Abdeldayem, Jakub Markiewicz, Kunal Kansara, Laura Edwards
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Airborne Laser Scanning (ALS) is one of the main technologies for generating high-resolution digital terrain models (DTMs). DTMs are crucial to several applications, such as topographic mapping, flood zone delineation, geographic information systems (GIS), hydrological modelling, spatial analysis, etc. Laser scanning system generates irregularly spaced three-dimensional cloud of points. Raw ALS data are mainly ground points (that represent the bare earth) and non-ground points (that represent buildings, trees, cars, etc.). Removing all the non-ground points from the raw data is referred to as filtering. Filtering heavily forested areas is considered a difficult and challenging task as the canopy stops laser pulses from reaching the terrain surface. This research presents an approach for removing non-ground points from raw ALS data in densely forested areas. Smoothing splines are exploited to interpolate and fit the noisy ALS data. The presented filter utilizes a weight function to allocate weights for each point of the data. Furthermore, unlike most of the methods, the presented filtering algorithm is designed to be automatic. Three different forested areas in the United Kingdom are used to assess the performance of the algorithm. The results show that the generated DTMs from the filtered data are accurate (when compared against reference terrain data) and the performance of the method is stable for all the heavily forested data samples. The average root mean square error (RMSE) value is 0.35 m.Keywords: airborne laser scanning, digital terrain models, filtering, forested areas
Procedia PDF Downloads 1391021 Micromechanical Compatibility Between Cells and Scaffold Mediates the Efficacy of Regenerative Medicine
Authors: Li Yang, Yang Song, Martin Y. M. Chiang
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Objective: To experimentally substantiate the micromechanical compatibility between cell and scaffold, in the regenerative medicine approach for restoring bone volume, is essential for phenotypic transitions Methods: Through nanotechnology and electrospinning process, nanofibrous scaffolds were fabricated to host dental follicle stem cells (DFSCs). Blends (50:50) of polycaprolactone (PCL) and silk fibroin (SF), mixed with various content of cellulose nanocrystals (CNC, up to 5% in weight), were electrospun to prepare nanofibrous scaffolds with heterogeneous microstructure in terms of fiber size. Colloidal probe atomic force microscopy (AFM) and conventional uniaxial tensile tests measured the scaffold stiffness at the micro-and macro-scale, respectively. The cell elastic modulus and cell-scaffold adhesive interaction (i.e., a chemical function) were examined through single-cell force spectroscopy using AFM. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine if the mechanotransduction signal (i.e., Yap1, Wwr2, Rac1, MAPK8, Ptk2 and Wnt5a) is upregulated by the scaffold stiffness at the micro-scale (cellular scale). Results: The presence of CNC produces fibrous scaffolds with a bimodal distribution of fiber diameter. This structural heterogeneity, which is CNC-composition dependent, remarkably modulates the mechanical functionality of scaffolds at microscale and macroscale simultaneously, but not the chemical functionality (i.e., only a single material property is varied). In in vitro tests, the osteogenic differentiation and gene expression associated with mechano-sensitive cell markers correlate to the degree of micromechanical compatibility between DFSCs and the scaffold. Conclusion: Cells require compliant scaffolds to encourage energetically favorable interactions for mechanotransduction, which are converted into changes in cellular biochemistry to direct the phenotypic evolution. The micromechanical compatibility is indeed important to the efficacy of regenerative medicine.Keywords: phenotype transition, scaffold stiffness, electrospinning, cellulose nanocrystals, single-cell force spectroscopy
Procedia PDF Downloads 1901020 Ultrasensitive Detection and Discrimination of Cancer-Related Single Nucleotide Polymorphisms Using Poly-Enzyme Polymer Bead Amplification
Authors: Lorico D. S. Lapitan Jr., Yihan Xu, Yuan Guo, Dejian Zhou
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The ability of ultrasensitive detection of specific genes and discrimination of single nucleotide polymorphisms is important for clinical diagnosis and biomedical research. Herein, we report the development of a new ultrasensitive approach for label-free DNA detection using magnetic nanoparticle (MNP) assisted rapid target capture/separation in combination with signal amplification using poly-enzyme tagged polymer nanobead. The sensor uses an MNP linked capture DNA and a biotin modified signal DNA to sandwich bind the target followed by ligation to provide high single-nucleotide polymorphism discrimination. Only the presence of a perfect match target DNA yields a covalent linkage between the capture and signal DNAs for subsequent conjugation of a neutravidin-modified horseradish peroxidase (HRP) enzyme through the strong biotin-nuetravidin interaction. This converts each captured DNA target into an HRP which can convert millions of copies of a non-fluorescent substrate (amplex red) to a highly fluorescent product (resorufin), for great signal amplification. The use of polymer nanobead each tagged with thousands of copies of HRPs as the signal amplifier greatly improves the signal amplification power, leading to greatly improved sensitivity. We show our biosensing approach can specifically detect an unlabeled DNA target down to 10 aM with a wide dynamic range of 5 orders of magnitude (from 0.001 fM to 100.0 fM). Furthermore, our approach has a high discrimination between a perfectly matched gene and its cancer-related single-base mismatch targets (SNPs): It can positively detect the perfect match DNA target even in the presence of 100 fold excess of co-existing SNPs. This sensing approach also works robustly in clinical relevant media (e.g. 10% human serum) and gives almost the same SNP discrimination ratio as that in clean buffers. Therefore, this ultrasensitive SNP biosensor appears to be well-suited for potential diagnostic applications of genetic diseases.Keywords: DNA detection, polymer beads, signal amplification, single nucleotide polymorphisms
Procedia PDF Downloads 2491019 Simulation of Optimal Runoff Hydrograph Using Ensemble of Radar Rainfall and Blending of Runoffs Model
Authors: Myungjin Lee, Daegun Han, Jongsung Kim, Soojun Kim, Hung Soo Kim
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Recently, the localized heavy rainfall and typhoons are frequently occurred due to the climate change and the damage is becoming bigger. Therefore, we may need a more accurate prediction of the rainfall and runoff. However, the gauge rainfall has the limited accuracy in space. Radar rainfall is better than gauge rainfall for the explanation of the spatial variability of rainfall but it is mostly underestimated with the uncertainty involved. Therefore, the ensemble of radar rainfall was simulated using error structure to overcome the uncertainty and gauge rainfall. The simulated ensemble was used as the input data of the rainfall-runoff models for obtaining the ensemble of runoff hydrographs. The previous studies discussed about the accuracy of the rainfall-runoff model. Even if the same input data such as rainfall is used for the runoff analysis using the models in the same basin, the models can have different results because of the uncertainty involved in the models. Therefore, we used two models of the SSARR model which is the lumped model, and the Vflo model which is a distributed model and tried to simulate the optimum runoff considering the uncertainty of each rainfall-runoff model. The study basin is located in Han river basin and we obtained one integrated runoff hydrograph which is an optimum runoff hydrograph using the blending methods such as Multi-Model Super Ensemble (MMSE), Simple Model Average (SMA), Mean Square Error (MSE). From this study, we could confirm the accuracy of rainfall and rainfall-runoff model using ensemble scenario and various rainfall-runoff model and we can use this result to study flood control measure due to climate change. Acknowledgements: This work is supported by the Korea Agency for Infrastructure Technology Advancement(KAIA) grant funded by the Ministry of Land, Infrastructure and Transport (Grant 18AWMP-B083066-05).Keywords: radar rainfall ensemble, rainfall-runoff models, blending method, optimum runoff hydrograph
Procedia PDF Downloads 2801018 Non Linear Stability of Non Newtonian Thin Liquid Film Flowing down an Incline
Authors: Lamia Bourdache, Amar Djema
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The effect of non-Newtonian property (power law index n) on traveling waves of thin layer of power law fluid flowing over an inclined plane is investigated. For this, a simplified second-order two-equation model (SM) is used. The complete model is second-order four-equation (CM). It is derived by combining the weighted residual integral method and the lubrication theory. This is due to the fact that at the beginning of the instability waves, a very small number of waves is observed. Using a suitable set of test functions, second order terms are eliminated from the calculus so that the model is still accurate to the second order approximation. Linear, spatial, and temporal stabilities are studied. For travelling waves, a particular type of wave form that is steady in a moving frame, i.e., that travels at a constant celerity without changing its shape is studied. This type of solutions which are characterized by their celerity exists under suitable conditions, when the widening due to dispersion is balanced exactly by the narrowing effect due to the nonlinearity. Changing the parameter of celerity in some range allows exploring the entire spectrum of asymptotic behavior of these traveling waves. The (SM) model is converted into a three dimensional dynamical system. The result is that the model exhibits bifurcation scenarios such as heteroclinic, homoclinic, Hopf, and period-doubling bifurcations for different values of the power law index n. The influence of the non-Newtonian parameter on the nonlinear development of these travelling waves is discussed. It is found at the end that the qualitative characters of bifurcation scenarios are insensitive to the variation of the power law index.Keywords: inclined plane, nonlinear stability, non-Newtonian, thin film
Procedia PDF Downloads 2831017 The Effect of a Probiotic Diet on htauE14 in a Rodent Model of Alzheimer’s Disease
Authors: C. Flynn, Q. Yuan, C. Reinhardt
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Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder affecting broad areas of the cerebral cortex and hippocampus. More than 95% of AD cases are representative of sporadic AD, where both genetic and environmental risk factors play a role. The main pathological features of AD include the widespread deposition of amyloid-beta and neurofibrillary tau tangles in the brain. The earliest brain pathology related to AD has been defined as hyperphosphorylated soluble tau in the noradrenergic locus coeruleus (LC) neurons, characterized by Braak. However, the cause of this pathology and the ultimate progression of AD is not understood. Increasing research points to a connection between the gut microbiota and the brain, and mounting evidence has shown that there is a bidirectional interaction between the two, known as the gut-brain axis. This axis can allow for bidirectional movement of neuroinflammatory cytokines and pathogenic misfolded proteins, as seen in AD. Prebiotics and probiotics have been shown to have a beneficial effect on gut health and can strengthen the gut-barrier as well as the blood-brain barrier, preventing the spread of these pathogens across the gut-brain axis. Our laboratory has recently established a pretangle tau rat model, in which we selectively express pseudo-phosphorylated human tau (htauE14) in the LC neurons of TH-Cre rats. LC htauE14 produced pathological changes in rats resembling those of the preclinical AD pathology (reduced olfactory discrimination and LC degeneration). In this work, we will investigate the effects of pre/probiotic ingestion on AD behavioral deficits, blood inflammation/cytokines, and various brain markers in our experimental rat model of AD. Rats will be infused with an adeno-associated viral vector containing a human tau gene pseudophosphorylated at 14 sites (common in LC pretangles) into 2-3 month TH-Cre rats. Fecal and blood samples will be taken at pre-surgery, and various post-surgery time points. A collection of behavioral tests will be performed, and immunohistochemistry/western blotting techniques will be used to observe various biomarkers. This work aims to elucidate the relationship between gut health and AD progression by strengthening gut-brain relationship and aims to observe the overall effect on tau formation and tau pathology in AD brains.Keywords: alzheimer’s disease, aging, gut microbiome, neurodegeneration
Procedia PDF Downloads 1371016 Molecular Diversity of Forensically Relevant Insects from the Cadavers of Lahore
Authors: Sundus Mona, Atif Adnan, Babar Ali, Fareeha Arshad, Allah Rakha
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Molecular diversity is the variation in the abundance of species. Forensic entomology is a neglected field in Pakistan. Insects collected from the crime scene should be handled by forensic entomologists who are currently virtually non-existent in Pakistan. Correct identification of insect specimen along with knowledge of their biodiversity can aid in solving many problems related to complicated forensic cases. Inadequate morphological identification and insufficient thermal biological studies limit the entomological utility in Forensic Medicine. Recently molecular identification of entomological evidence has gained attention globally. DNA barcoding is the latest and established method for species identification. Only proper identification can provide a precise estimation of postmortem intervals. Arthropods are known to be the first tourists scavenging on decomposing dead matter. The objective of the proposed study was to identify species by molecular techniques and analyze their phylogenetic importance with barcoded necrophagous insect species of early succession on human cadavers. Based upon this identification, the study outcomes will be the utilization of established DNA bar codes to identify carrion feeding insect species for concordant estimation of post mortem interval. A molecular identification method involving sequencing of a 658bp ‘barcode’ fragment of the mitochondrial cytochrome oxidase subunit 1 (CO1) gene from collected specimens of unknown dipteral species from cadavers of Lahore was evaluated. Nucleotide sequence divergences were calculated using MEGA 7 and Arlequin, and a neighbor-joining phylogenetic tree was generated. Three species were identified, Chrysomya megacephala, Chrysomya saffranea, and Chrysomya rufifacies with low genetic diversity. The fixation index was 0.83992 that suggests a need for further studies to identify and classify forensically relevant insects in Pakistan. There is an exigency demand for further research especially when immature forms of arthropods are recovered from the crime scene.Keywords: molecular diversity, DNA barcoding, species identification, forensically relevant
Procedia PDF Downloads 1491015 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology
Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal
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Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling
Procedia PDF Downloads 2221014 Changes in the fecal Microbiome of Periparturient Dairy Cattle and Associations with the Onset of Salmonella Shedding
Authors: Lohendy Munoz-Vargas, Stephen O. Opiyo, Rose Digianantonio, Michele L. Williams, Asela Wijeratne, Gregory Habing
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Non-typhoidal Salmonella enterica is a zoonotic pathogen with critical importance in animal and public health. The persistence of Salmonella on farms affects animal productivity and health, and represents a risk for food safety. The intestinal microbiota plays a fundamental role in the colonization and invasion of this ubiquitous microorganism. To overcome the colonization resistance imparted by the gut microbiome, Salmonella uses invasion strategies and the host inflammatory response to survive, proliferate, and establish infections with diverse clinical manifestations. Cattle serve as reservoirs of Salmonella, and periparturient cows have high prevalence of Salmonella shedding; however, to author`s best knowledge, little is known about the association between the gut microbiome and the onset of Salmonella shedding during the periparturient period. Thus, the objective of this study was to assess the association between changes in bacterial communities and the onset of Salmonella shedding in cattle approaching parturition. In a prospective cohort study, fecal samples from 98 dairy cows originating from four different farms were collected at four time points relative to calving (-3 wks, -1 wk, +1 wk, +3 wks). All 392 samples were cultured for Salmonella. Sequencing of the V4 region of the 16S rRNA gene using the Illumina platform was completed to evaluate the fecal microbiome in a selected sample subset. Analyses of microbial composition, diversity, and structure were performed according to time points, farm, and Salmonella onset status. Individual cow fecal microbiomes, predominated by Bacteroidetes, Firmicutes, Spirochaetes, and Proteobacteria phyla, significantly changed before and after parturition. Microbial communities from different farms were distinguishable based on multivariate analysis. Although there were significant differences in some bacterial taxa between Salmonella positive and negative samples, our results did not identify differences in the fecal microbial diversity or structure for cows with and without the onset of Salmonella shedding. These data suggest that determinants other than the significant changes in the fecal microbiome influence the periparturient onset of Salmonella shedding in dairy cattle.Keywords: dairy cattle, microbiome, periparturient, Salmonella
Procedia PDF Downloads 1731013 Social Interaction Dynamics Exploration: The Case Study of El Sherouk City
Authors: Nardine El Bardisy, Wolf Reuter, Ayat Ismail
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In Egypt, there is continuous housing demand as a result of rapid population growth. In 1979, this forced the government to establish new urban communities in order to decrease stress around delta. New Urban Communities Authority (NUCA) was formulated to take the responsibly of this new policy. These communities suffer from social life deficiency due to their typology, which is separated island with barriers. New urban communities’ typology results from the influence of neoliberalism movement and modern city planning forms. The lack of social interaction in these communities at present should be enhanced in the future. On a global perspective, sustainable development calls for creating more sustainable communities which include social, economic and environmental aspects. From 1960, planners were highly focusing on the promotion of the social dimension in urban development plans. The research hypothesis states: “It is possible to promote social interaction in new urban communities through a set of socio-spatial recommended strategies that are tailored for Greater Cairo Region context”. In order to test this hypothesis, the case of El-Sherouk city is selected, which represents the typical NUCA development plans. Social interaction indicators were derived from literature and used to explore different social dynamics in the selected case. The tools used for exploring case study are online questionnaires, face to face questionnaires, interviews, and observations. These investigations were analyzed, conclusions and recommendations were set to improve social interaction.Keywords: new urban communities, modern planning, social interaction, social life
Procedia PDF Downloads 1251012 The Assessment of Particulate Matter Pollution in Kaunas Districts
Authors: Audrius Dedele, Aukse Miskinyte
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Air pollution is a major problem, especially in large cities, causing a variety of environmental issues and a risk to human health effects. In order to observe air quality, to reduce and control air pollution in the city, municipalities are responsible for the creation of air quality management plans, air quality monitoring and emission inventories. Atmospheric dispersion modelling systems, along with monitoring, are powerful tools, which can be used not only for air quality management, but for the assessment of human exposure to air pollution. These models are widely used in epidemiological studies, which try to determine the associations between exposure to air pollution and the adverse health effects. The purpose of this study was to determine the concentration of particulate matter smaller than 10 μm (PM10) in different districts of Kaunas city during winter season. ADMS-Urban dispersion model was used for the simulation of PM10 pollution. The inputs of the model were the characteristics of stationary, traffic and domestic sources, emission data, meteorology and background concentrations were entered in the model. To assess the modelled concentrations of PM10 in Kaunas districts, geographic information system (GIS) was used. More detailed analysis was made using Spatial Analyst tools. The modelling results showed that the average concentration of PM10 during winter season in Kaunas city was 24.8 µg/m3. The highest PM10 levels were determined in Zaliakalnis and Aleksotas districts with are the highest number of individual residential properties, 32.0±5.2 and 28.7±8.2 µg/m3, respectively. The lowest pollution of PM10 was modelled in Petrasiunai district (18.4 µg/m3), which is characterized as commercial and industrial neighbourhood.Keywords: air pollution, dispersion model, GIS, Particulate matter
Procedia PDF Downloads 2691011 Soil Salinity from Wastewater Irrigation in Urban Greenery
Authors: H. Nouri, S. Chavoshi Borujeni, S. Anderson, S. Beecham, P. Sutton
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The potential risk of salt leaching through wastewater irrigation is of concern for most local governments and city councils. Despite the necessity of salinity monitoring and management in urban greenery, most attention has been on agricultural fields. This study was defined to investigate the capability and feasibility of monitoring and predicting soil salinity using near sensing and remote sensing approaches using EM38 surveys, and high-resolution multispectral image of WorldView3. Veale Gardens within the Adelaide Parklands was selected as the experimental site. The results of the near sensing investigation were validated by testing soil salinity samples in the laboratory. Over 30 band combinations forming salinity indices were tested using image processing techniques. The outcomes of the remote sensing and near sensing approaches were compared to examine whether remotely sensed salinity indicators could map and predict the spatial variation of soil salinity through a potential statistical model. Statistical analysis was undertaken using the Stata 13 statistical package on over 52,000 points. Several regression models were fitted to the data, and the mixed effect modelling was selected the most appropriate one as it takes to account the systematic observation-specific unobserved heterogeneity. Results showed that SAVI (Soil Adjusted Vegetation Index) was the only salinity index that could be considered as a predictor for soil salinity but further investigation is needed. However, near sensing was found as a rapid, practical and realistically accurate approach for salinity mapping of heterogeneous urban vegetation.Keywords: WorldView3, remote sensing, EM38, near sensing, urban green spaces, green smart cities
Procedia PDF Downloads 1621010 Liver and Liver Lesion Segmentation From Abdominal CT Scans
Authors: Belgherbi Aicha, Hadjidj Ismahen, Bessaid Abdelhafid
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The interpretation of medical images benefits from anatomical and physiological priors to optimize computer- aided diagnosis applications. Segmentation of liver and liver lesion is regarded as a major primary step in computer aided diagnosis of liver diseases. Precise liver segmentation in abdominal CT images is one of the most important steps for the computer-aided diagnosis of liver pathology. In this papers, a semi- automated method for medical image data is presented for the liver and liver lesion segmentation data using mathematical morphology. Our algorithm is currency in two parts. In the first, we seek to determine the region of interest by applying the morphological filters to extract the liver. The second step consists to detect the liver lesion. In this task; we proposed a new method developed for the semi-automatic segmentation of the liver and hepatic lesions. Our proposed method is based on the anatomical information and mathematical morphology tools used in the image processing field. At first, we try to improve the quality of the original image and image gradient by applying the spatial filter followed by the morphological filters. The second step consists to calculate the internal and external markers of the liver and hepatic lesions. Thereafter we proceed to the liver and hepatic lesions segmentation by the watershed transform controlled by markers. The validation of the developed algorithm is done using several images. Obtained results show the good performances of our proposed algorithmKeywords: anisotropic diffusion filter, CT images, hepatic lesion segmentation, Liver segmentation, morphological filter, the watershed algorithm
Procedia PDF Downloads 4511009 Identification of Rare Mutations in Genes Involved in Monogenic Forms of Obesity and Diabetes in Obese Guadeloupean Children through Next-Generation Sequencing
Authors: Lydia Foucan, Laurent Larifla, Emmanuelle Durand, Christine Rambhojan, Veronique Dhennin, Jean-Marc Lacorte, Philippe Froguel, Amelie Bonnefond
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In the population of Guadeloupe Island (472,124 inhabitants and 80% of subjects of African descent), overweight and obesity were estimated at 23% and 9% respectively among children. High prevalence of diabetes has been reported (~10%) in the adult population. Nevertheless, no study has investigated the contribution of gene mutations to childhood obesity in this population. We aimed to investigate rare genetic mutations in genes involved in monogenic obesity or diabetes in obese Afro-Caribbean children from Guadeloupe Island using next-generation sequencing. The present investigation included unrelated obese children, from a previous study on overweight conducted in Guadeloupe Island in 2013. We sequenced coding regions of 59 genes involved in monogenic obesity or diabetes. A total of 25 obese schoolchildren (with Z-score of body mass index [BMI]: 2.0 to 2.8) were screened for rare mutations (non-synonymous, splice-site, or insertion/deletion) in 59 genes. Mean age of the study population was 12.4 ± 1.1 years. Seventeen children (68%) had insulin-resistance (HOMA-IR > 3.16). A family history of obesity (mother or father) was observed in eight children and three of the accompanying parent presented with type 2 diabetes. None of the children had gonadotrophic abnormality or mental retardation. We detected five rare heterozygous mutations, in four genes involved in monogenic obesity, in five different obese children: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations which were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations which were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutation in ABCC8 or KCNJ11 (involved in monogenic diabetes), which were of uncertain significance (KCNJ11 p.Val13Met, KCNJ11 p.Val151Met, ABCC8 p.Lys1521Asn and ABCC8 p.Ala625Val). Rare pathogenic or likely pathogenic mutations, linked to severe obesity were detected in more than 15% of this Afro-Caribbean population at high risk of obesity and type 2 diabetes.Keywords: childhood obesity, MC4R, monogenic obesity, SIM1
Procedia PDF Downloads 1931008 Chitosan Hydrogel Containing Nitric Oxide Donors with Potent Antibacterial Effect
Authors: Milena Trevisan Pelegrino, Bruna De Araujo Lima, Mônica H. M. Do Nascimento, Christiane B. Lombello, Marcelo Brocchi, Amedea B. Seabra
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Nitric oxide (NO) is a small molecule involved in a wide range of physiological and pathophysiological processes, including vasodilatation, control of inflammatory pain, wound healing, and antibacterial activities. As NO is a free radical, the design of drugs that generates therapeutic amounts of NO in controlled spatial and time manners is still a challenge. In this study, the NO donor S-nitrosoglutathione (GSNO) was incorporated into the thermoresponsive Pluronic F-127 (PL) - chitosan (CS) hydrogel, in an easy and economically feasible methodology. CS is a polysaccharide with known antimicrobial and biocompatibility properties. Scanning electron microscopy, rheology and differential scanning calorimetry techniques were used for hydrogel characterization. The results demonstrated that the hydrogel has a smooth surface, thermoresponsive behavior, and good mechanical stability. The kinetics of NO release and GSNO diffusion from GSNO-containing PL/CS hydrogel demonstrated a sustained NO/GSNO release, in concentrations suitable for biomedical applications, at physiological and skin temperatures. The GSNO-PL/CS hydrogel demonstrated a concentration-dependent toxicity to Vero cells, and antimicrobial activity to Pseudomonas aeruginosa (minimum inhibitory concentration and minimum bactericidal concentration values of 0.5 µg·mL-1 of hydrogel, which correspondents to 1 mmol·L-1 of GSNO). Interesting, the concentration range in which the NO-releasing hydrogel demonstrated antibacterial effect was not found toxic to Vero mammalian cell. Thus, GSNO-PL/CS hydrogel is suitable biomaterial for topical NO delivery applications.Keywords: antimicrobial, chitosan, biocompatibility, S-nitrosothiols
Procedia PDF Downloads 1851007 Comparative Functional Analysis of Two Major Sterol-Biosynthesis Regulating Transcription Factors, Hob1 and Sre1, in Pathogenic Cryptococcus Species Complex
Authors: Dong-Gi Lee, Suyeon Cha, Yong-Sun Bahn
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Sterol lipid is essential for cell membrane structure in eukaryotic cells. In mammalian cells, sterol regulatory element binding proteins (SREBPs) act as principal regulators of cellular cholesterol which is essential for proper cell membrane fluidity and structure. SREBP and sterol regulation are related to levels of cellular oxygen because it is a major substrate for sterol synthesis. Upon cellular sterol and oxygen levels are depleted, SREBP is translocated to the Golgi where it undergoes proteolytic cleavage of N terminus, then it travels to the nucleus to play a role as transcription factor. In yeast cells, synthesis of ergosterol is also highly oxygen consumptive, and Sre1 is a transcription factor known to play a central role in adaptation to growth under low oxygen condition and sterol homeostasis in Cryptococcus neoformans. In this study, we observed phenotypes in other strains of Cryptococcus species by constructing hob1Δ and sre1Δ mutants to confirm whether the functions of both genes are conserved in most serotypes. As a result, hob1Δ showed no noticeable phenotype under treatment of antifungal drugs and most environmental stresses in R265 (C. gattii) and XL280 (C. neoformans), suggesting that Hob1 is related to sterol regulation only in H99 (serotype A). On the other hand, the function of Sre1 was found to be conserved in most serotypes. Furthermore, mating experiment of hob1Δ or sre1Δ showed dramatic defects in serotype A (H99) and D (XL280). It revealed that Hob1 and Sre1 related to mating ability in Cryptococcus species, especially cell fusion efficiency. In conclusion, HOB1 and SRE1 play crucial role in regulating sterol-homeostasis and differentiation in C. neoformans, moreover, Hob1 is specific gene in Cryptococcus neoformans. It suggests that Hob1 is considered as potent factor-targeted new safety antifungal drug.Keywords: cryptococcus neoformans, Hob1, Sre1, sterol regulatory element binding proteins
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