Search results for: loci

Authors: M. Chukhryaeva, R. Skhalyakho, J. Kagazegeva, E. Pocheshkhova, L. Yepiskopossyan, O. Balanovsky, E. Balanovska

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The Middle East is crossroad of different populations at different times. The Kurds are of particular interest in this region. Historical sources suggested that the origin of the Kurds is associated with Medes. Therefore, it was especially interesting to compare gene pool of Kurds with other supposed descendants of Medes-Tats. Yezidis are ethno confessional group of Kurds. Yezidism as a confessional teaching was formed in the XI-XIII centuries in Iraq. Yezidism has caused reproductively isolation of Yezidis from neighboring populations for centuries. Also, isolation helps to retain Yezidian caste system. It is unknown how the history of Yezidis affected its genу pool because it has never been the object of researching. We have examined the Y-chromosome variation in Yezidis and Kurdish males to understand their gene pool. We collected DNA samples from 90 Yezidi males and 24 Kurdish males together with their pedigrees. We performed Y-STR analysis of 17 loci in the samples collected (Yfiler system from Applied Biosystems) and analysis of 42 Y-SNPs by real-time PCR. We compared our data with published data from other Kurdish groups and from European, Caucasian, and West Asian populations. We found that gene pool of Yezidis contains haplogroups common in the Middle East (J-M172(xM67,M12)- 24%, E-M35(xM78)- 9%) and in South Western Asia (R-M124- 8%) and variant with wide distribution area - R-M198(xM458- 9%). The gene pool of Kurdish has higher genetic diversity than Yezidis. Their dominants haplogroups are R-M198- 20,3 %, E-M35- 9%, J-M172- 9%. Multidimensional scaling also shows that the Kurds and Yezidis are part of the same frontier Asian cluster, which, in addition, included Armenians, Iranians, Turks, and Greeks. At the same time, the peoples of the Caucasus and Europe form isolated clusters that do not overlap with the Asian clusters. It is noteworthy that Kurds from our study gravitate towards Tats, which indicates that most likely these two populations are descendants of ancient Medes population. Multidimensional scaling also reveals similarity between gene pool of Yezidis, Kurds with Armenians and Iranians. The analysis of Yezidis pedigrees and their STR variability did not reveal a reliable connection between genetic diversity and caste system. This indicates that the Yezidis caste system is a social division and not a biological one. Thus, we showed that, despite many years of isolation, the gene pool of Yezidis retained a common layer with the gene pool of Kurds, these populations have common spectrum of haplogroups, but Yezidis have lower genetic diversity than Kurds. This study received primary support from the RSF grant No. 16-36-00122 to MC and grant No. 16-06-00364 to EP.

Keywords: gene pool, haplogroup, Kurds, SNP and STR markers, Yezidis

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Authors: Abejide Dorcas Ropo, , Falusi Olamide Ahmed, Daudu Oladipupo Abdulazeez Yusuf, Salihu Bolaji Zuluquri Neen, Muhammad Liman Muhammad, Gado Aishatu Adamu

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Water stress is a major factor limiting the productivity of crops in the world today. This study evaluated the morpho-agronomic response of twenty-four (24) Nigerian Bambara groundnut landraces to water stress and genetic diversity of some selected accessions using SSR markers. The studies was carried out in the Botanical garden of the Department of Plant Biology, Federal University of Technology, Minna, Niger State, Nigeria in a randomized complete block design using three replicates. Molecular analysis using SSR primers was carried out at the Centre for Bio- Science, International Institute of Tropical Agriculture (IITA) Ibadan, Nigeria in order to characterize ten selected accessions comprising of the seven most drought tolerant and the three most susceptible accessions detected from the morpho-agronomic studies. Results revealed that water stress decreased morpho-agronomic traits such as plant height, leaf area, number of leaves per plant and seed yield etc. A total of 22 alleles were detected by the SSR markers used with a mean number of 4 allelles. Simple Sequence Repeat (SSR) markers MBamCO33, Primer 65 and G358B2-D15 each detected 4 allelles while Primer 3FR and 4FR detected 5 allelles each. The study revealed significantly high polymorphisms in 10 Loci. The mean value of Polymorpic information content was 0.6997 implying the usefulness of the primers used in identifying genetic similarities and differences among the Bambara groundnut genotypes. The SSR analysis revealed a comparable pattern between genetic diversity and drought tolerance of the genotypes. The Unweighted Paired Group Method with Arithmethic Mean (UPGMA) dendrogram showed that at a genetic distance of 0.1, the accessions were grouped into three groups according to their level of tolerance to drought. The two most drought tolerant accessions were grouped together and the 5th and 6th most drought tolerant accession were also grouped together. This suggests that the genotypes grouped together may be genetically close, may possess similar genes or have a common origin. The degree of genetic variants obtained could be useful in bambara groundnut breeding for drought tolerance. The identified drought tolerant bambara groundnut landraces are important genetic resources for drought stress tolerance breeding programme of bambara groundnut. The genotypes are also useful for germplasm conservation and global implications.

Keywords: bambara groundnut, genetic diversity, germplasm, SSR markers, water stress

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Authors: P. M. Sreekanth

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Teak (Tectona grandis L. f.) is a tree species indigenous to India and other Southeastern countries. It produces high-value timber and is easily established in plantations. Reforestation requires a constant supply of high quality seeds. Seed Production Areas (SPA) of teak are improved stands used for collection of open-pollinated quality seeds in large quantities. Information on the genetic diversity of major teak SPAs in India is scanty. The genetic structure of four important seed production areas of Kerala State in Southern India was analyzed employing amplified fragment length polymorphism markers using ten selective primer combinations on 80 samples (4 populations X 20 trees). The study revealed that the gene diversity of the SPAs varied from 0.169 (Konni SPA) to 0.203 (Wayanad SPA). The percentage of polymorphic loci ranged from 74.42 (Parambikulam SPA) to 84.06 (Konni SPA). The mean total gene diversity index (HT) of all the four SPAs was 0.2296 ±0.02. A high proportion of genetic diversity was observed within the populations (83%) while diversity between populations was lower (17%) (GST = 0.17). Principal coordinate analysis and STRUCTURE analysis of the genotypes indicated that the pattern of clustering was in accordance with the origin and geographic location of SPAs, indicating specific identity of each population. A UPGMA dendrogram was prepared and showed that all the twenty samples from each of Konni and Parambikulam SPAs clustered into two separate groups, respectively. However, five Nilambur genotypes and one Wayanad genotype intruded into the Konni cluster. The higher gene flow estimated (Nm = 2.4) reflected the inclusion of Konni origin planting stock in the Nilambur and Wayanad plantations. Evidence for population structure investigated using 3D Principal Coordinate Analysis of FAMD software 1.30 indicated that the pattern of clustering was in accordance with the origin of SPAs. The present study showed that assessment of genetic diversity in seed production plantations can be achieved using AFLP markers. The AFLP fingerprinting was also capable of identifying the geographical origin of planting stock and there by revealing the occurrence of the errors in genotype labeling. Molecular marker-based selective culling of genetically similar trees from a stand so as to increase the genetic base of seed production areas could be a new proposition to improve quality of seeds required for raising commercial plantations of teak. The technique can also be used to assess the genetic diversity status of plus trees within provenances during their selection for raising clonal seed orchards for assuring the quality of seeds available for raising future plantations.

Keywords: AFLP, genetic structure, spa, teak

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Authors: Ciro Moreno-Ramirez, Maria Tomas-Rodriguez, Simos A. Evangelou

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A motorcycle's front end links the front wheel to the motorcycle's chassis and has two main functions: the front wheel suspension and the vehicle steering. Up to this date, several suspension systems have been developed in order to achieve the best possible front end behavior, being the telescopic fork the most common one and already subjected to several years of study in terms of its kinematics, dynamics, stability and control. A motorcycle telescopic fork suspension model consists of a couple of outer tubes which contain the suspension components (coil springs and dampers) internally and two inner tubes which slide into the outer ones allowing the suspension travel. The outer tubes are attached to the frame through two triple trees which connect the front end to the main frame through the steering bearings and allow the front wheel to turn about the steering axis. This system keeps the front wheel's displacement in a straight line parallel to the steering axis. However, there exist alternative suspension designs that allow different trajectories of the front wheel with the suspension travel. In this contribution, the authors investigate an alternative front suspension system (Hossack suspension) and its influence on the motorcycle nonlinear dynamics to identify and reduce stability risks that a new suspension systems may introduce in the motorcycle dynamics. Based on an existing high-fidelity motorcycle mathematical model, the front end geometry is modified to accommodate a Hossack suspension system. It is characterized by a double wishbone design that varies the front end geometry on certain maneuverings and, consequently, the machine's behavior/response. It consists of a double wishbone structure directly attached to the chassis. In here, the kinematics of this system and its impact on the motorcycle performance/stability are analyzed and compared to the well known telescopic fork suspension system. The framework of this research is the mathematical modelling and numerical simulation. Full stability analyses are performed in order to understand how the motorcycle dynamics may be affected by the newly introduced front end design. This study is carried out by a combination of nonlinear dynamical simulation and root-loci methods. A modal analysis is performed in order to get a deeper understanding of the different modes of oscillation and how the Hossack suspension system affects them. The results show that different kinematic designs of a double wishbone suspension systems do not modify the general motorcycle's stability. The normal modes properties remain unaffected by the new geometrical configurations. However, these normal modes differ from one suspension system to the other. It is seen that the normal modes behaviour depends on various important dynamic parameters, such as the front frame flexibility, the steering damping coefficient and the centre of mass location.

Keywords: nonlinear mechanical systems, motorcycle dynamics, suspension systems, stability

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Authors: Alfonsina Buoniconto

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The aim of this study is to investigate the degree of cross-linguistic and intra-linguistic variation in the encoding of motion events (MEs) in English and Italian, these being typologically different languages both showing signs of disobedience to their respective types. As a matter of fact, the traditional typological classification of MEs encoding distributes languages into two macro-types, based on the preferred locus for the expression of Path, the main ME component (other components being Figure, Ground and Manner) characterized by conceptual and structural prominence. According to this model, Satellite-framed (SF) languages typically express Path information in verb-dependent items called satellites (e.g. preverbs and verb particles) with main verbs encoding Manner of motion; whereas Verb-framed languages (VF) tend to include Path information within the verbal locus, leaving Manner to adjuncts. Although this dichotomy is valid altogether, languages do not always behave according to their typical classification patterns. English, for example, is usually ascribed to the SF type due to the rich inventory of postverbal particles and phrasal verbs used to express spatial relations (i.e. the cat climbed down the tree); nevertheless, it is not uncommon to find constructions such as the fog descended slowly, which is typical of the VF type. Conversely, Italian is usually described as being VF (cf. Paolo uscì di corsa ‘Paolo went out running’), yet SF constructions like corse via in lacrime ‘She ran away in tears’ are also frequent. This paper will try to demonstrate that such a typological overlapping is due to the fact that the semantic units making up MEs are distributed within several loci of the sentence –not only verbs and satellites– thus determining a number of different constructions stemming from convergent factors. Indeed, the linguistic expression of motion events depends not only on the typological nature of languages in a traditional sense, but also on a series morphological, lexical, and syntactic resources, as well as on inferential, discursive, usage-related, and cultural factors that make semantic information more or less accessible, frequent, and easy to process. Hence, rather than describe English and Italian in dichotomic terms, this study focuses on the investigation of cross-linguistic and intra-linguistic variation in the use of all the strategies made available by each linguistic system to express motion. Evidence for these assumptions is provided by parallel corpora analysis. The sample texts are taken from two contemporary Italian novels and their respective English translations. The 400 motion occurrences selected (200 in English and 200 in Italian) were scanned according to the MODEG (an acronym for Motion Decoding Grid) methodology, which grants data comparability through the indexation and retrieval of combined morphosyntactic and semantic information at different levels of detail.

Keywords: construction typology, motion event encoding, parallel corpora, satellite-framed vs. verb-framed type

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Authors: Wu Liching

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Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.

Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders

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Authors: Supriya Ambawat, Subaran Singh, C. Tara Satyavathi, B. S. Rajpurohit, Ummed Singh, Balraj Singh

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Pearl millet [Pennisetum glaucum (L.) R. Br.] is an important staple food of the arid and semiarid tropical regions of Asia, Africa, and Latin America. It is rightly termed as nutricereal as it has high nutrition value and a good source of carbohydrate, protein, fat, ash, dietary fiber, potassium, magnesium, iron, zinc, etc. Pearl millet has low prolamine fraction and is gluten free which is useful for people having a gluten allergy. It has several health benefits like reduction in blood pressure, thyroid, diabe¬tes, cardiovascular and celiac diseases but its direct consumption as food has significantly declined due to several reasons. Keeping this in view, it is important to reorient the ef¬forts to generate demand through value-addition and quality improvement and create awareness on the nutritional merits of pearl millet. In India, through Indian Council of Agricultural Research-All India Coordinated Research Project on Pearl millet, multilocational coordinated trials for developed hybrids were conducted at various centers. The gene banks of pearl millet contain varieties with high levels of iron and zinc which were used to produce new pearl millet varieties with elevated iron levels bred with the high‐yielding varieties. Thus, using breeding approaches and biochemical analysis, a total of 167 hybrids and 61 varieties were identified and released for cultivation in different agro-ecological zones of the country which also includes some biofortified hybrids rich in Fe and Zn. Further, using several biotechnological interventions such as molecular markers, next-generation sequencing (NGS), association mapping, nested association mapping (NAM), MAGIC populations, genome editing, genotyping by sequencing (GBS), genome wide association studies (GWAS) advancement in millet improvement has become possible by identifying and tagging of genes underlying a trait in the genome. Using DArT markers very high density linkage maps were constructed for pearl millet. Improved HHB67 has been released using marker assisted selection (MAS) strategies, and genomic tools were used to identify Fe-Zn Quantitative Trait Loci (QTL). The draft genome sequence of millet has also opened various ways to explore pearl millet. Further, genomic positions of significantly associated simple sequence repeat (SSR) markers with iron and zinc content in the consensus map is being identified and research is in progress towards mapping QTLs for flour rancidity. The sequence information is being used to explore genes and enzymatic pathways responsible for rancidity of flour. Thus, development and application of several biotechnological approaches along with biofortification can accelerate the genetic gain targets for pearl millet improvement and help improve its quality.

Keywords: Biotechnological approaches, genomic tools, malnutrition, MAS, nutricereal, pearl millet, sequencing.

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Authors: Muhammad Asghar, Muhammad Ali, Farwah Batool

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Despite the general belief in Islam that figural representations should be avoided, particularly propagated by the Deobandis, a religious group influenced by Salafi and Wahhabi ideas, nevertheless the public interaction spaces such as Shops and offices are decorated with popular, mass-produced, modern devotional prints. This study seeks to focus on popular visual culture, its display in public interaction places such as shops and discusses how people establish relationships with images. The method adopted was basically ethnographic: to describe as precisely and completely as possible the phenomena to be studied, using the language and conceptual categories of the interlocutors themselves. This study has been enriched by ethnographic field research conducted during the months from October to December 2015 in the major cities of Punjab and their brief forays and surroundings where we explored how seeing upon images performs religious identity within the public space. The study examines the pattern of aesthetics and taste in the shops of especially common people whose sensibilities have not been refined or influenced by being exposed to any narrative or fine arts. Furthermore, it is our intention to question the general beliefs and opinions in the context of popular practices, the way in which people relate to these prints. The interpretations and analyses presented in this study illuminate how people create meaning through the display of such items of material culture in the immediate settings of their spaces. This study also seeks to demonstrate how popular Islam is practiced, transformed and understood through the display of popular representations of popular figures of piety like Sufi saints or their shrines are important to many believers and thus occupy important places in their shops. The findings are supported with empirical evidence and based on interviews with the shopkeepers, owners and office employees. Looking upon those popular modern devotional prints keeps people’s reverence of the personages alive. Because of their sacred themes they affect a relationship between the saint and the beholders as well as serve to symbolize and reinforce their belief since they become powerful loci of emotional attachment. Collectively such devotional prints satisfy a local taste to help people establish contact with God through the saints’ intercession in order to receive protection and benediction, and help in spiritual, mental and material problems. By putting all these facets of belief together we gain an insight into both the subjective and cognizant role that icons’ of saints play in the lives of believers. Their veneration through ingeniously contrived modern means of production makes a significant contribution to an understanding of how such imagery promotes a powerful belief in Sufi saints, which ultimately gives indications of how popular Islam is practiced and understood at its gross roots level.

Keywords: ethnographic field research, popular visual culture, protected space, religious identity

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Sandra Costa-Santos, Nadia Bertolino, Stephen Hicks, Vanessa May, Camilla Lewis

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This paper aims to elaborate the architectural theory on place-making that supported Claremont Court housing scheme (Edinburgh, United Kingdom). Claremont Court (1959-62) is a large post-war mixed development housing scheme designed by Basil Spence, which included ‘place-making’ as one of its founding principles. Although some stylistic readings of the housing scheme have been published, the theory on place-making that allegedly ruled the design has yet to be clarified. The architecture allows us to mark or make a place within space in order to dwell. Under the framework of contemporary philosophical theories of place, this paper aims to explore the relationship between place and dwelling through a cross-disciplinary reading of Claremont Court, with a view to develop an architectural theory on place-making. Since dwelling represents the way we are immersed in our world in an existential manner, this theme is not just relevant for architecture but also for philosophy and sociology. The research in this work is interpretive-historic in nature. It examines documentary evidence of the original architectural design, together with relevant literature in sociology, history, and architecture, through the lens of theories of place. First, the paper explores how the dwelling types originally included in Claremont Court supported ideas of dwelling or meanings of home. Then, it traces shared space and social ties in order to study the symbolic boundaries that allow the creation of a collective identity or sense of belonging. Finally, the relation between the housing scheme and the supporting theory is identified. The findings of this research reveal Scottish architect Basil Spence’s exploration of the meaning of home, as he changed his approach to the mass housing while acting as President of the Royal Incorporation of British Architects (1958-60). When the British Government was engaged in various ambitious building programmes, he sought to drive architecture to a wider socio-political debate as president of the RIBA, hence moving towards a more ambitious and innovative socio-architectural approach. Rather than trying to address the ‘genius loci’ with an architectural proposition, as has been stated, the research shows that the place-making theory behind the housing scheme was supported by notions of community-based on shared space and dispositions. The design of the housing scheme was steered by a desire to foster social relations and collective identities, rather than by the idea of keeping the spirit of the place. This research is part of a cross-disciplinary project funded by the Arts and Humanities Research Council. The findings present Claremont Court as a signifier of Basil Spence’s attempt to address the post-war political debate on housing in United Kingdom. They highlight the architect’s theoretical agenda and challenge current purely stylistic readings of Claremont Court as they fail to acknowledge its social relevance.

Keywords: architectural theory, dwelling, place-making, post-war housing

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Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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Authors: Mohammadjavad Sotoudeheian, Soroush Nematollahi

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Crohn’s disease (CD) is a chronic gastrointestinal segment inflammation encompassing immune dysregulation in a genetically susceptible individual in response to the environmental triggers and interaction between the microbiome and immune system. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures and enteric fistulae. Increased production of Th1 and Th17-cell cytokines and defects in T-regulatory cells have been associated with CD. Th17-cells are essential for protection against extracellular pathogens, but their atypical activity can cause autoimmunity. Intrinsic defects in the control of programmed cell death in the mucosal T-cell compartment are strongly implicated in the pathogenesis of CD. The apoptosis defect in mucosal T-cells in CD has been endorsed as an imbalance of the Bcl-2 and the Bax. The immune system encounters foreign antigens through microbial colonization of mucosal surfaces or infections. In addition, FOSL downregulated IL-26 expression, a cytokine that marks inflammatory Th17-populations in patients suffering from CD. Furthermore, the expression of IL-23 is associated with the transcription factor primary leucine zipper transcription factor ATF-like (Batf). Batf-deficiency demonstrated the crucial role of Batf in colitis development. Batf and IL-23 mediate their effects by inducing IL-6 production. Strong association of IL-23R, Stat3, and Stat4 with IBD susceptibility point to a critical involvement of T-cells. IL-23R levels in transfer fistula were dependent on the AP-1 transcription factor JunB that additionally controlled levels of RORγt by facilitating DNA binding of Batf. T lymphocytes lacking JunB failed to induce IL-23- and Th17-mediated experimental colitis highlighting the relevance of JunB for the IL-23/ Th17 pathway. The absence of T-bet causes unrestrained Th17-cell differentiation. T-cells are central parts of immune-mediated colon fistula. Especially Th17-cells were highly prevalent in inflamed IBD tissues, as RORγt is effective in preventing colitis. Intraepithelial lymphocytes (IEL) contain unique T-cell subsets, including cells expressing RORγt. Increased activated Th17 and decreased T-regulatory cells in inflamed intestinal tissues had been seen. T-cells differentiate in response to many cytokines, including IL-1β, IL-6, IL-23, and TGF-β, into Th17-cells, a process which is critically dependent on the Batf. IL-23 promotes Th17-cell in the colon. Batf manages the generation of IL-23 induced IL-23R+ Th17-cells. Batf is necessary for TGF-β/IL-6-induced Th17-polarization. Batf-expressing T-cells are the core of T-cell-mediated colitis. The human-specific parts of three AP-1 transcription factors, FOSL1, FOSL2, and BATF, are essential during the early stages of Th17 differentiation. BATF supports the Th17 lineage. FOSL1, FOSL2, and BATF make possession of regulatory loci of genes in the Th17 lineage cascade. The AP1 transcription factor Batf is identified to control intestinal inflammation and seems to regulate pathways within lymphocytes, which could theoretically control the expression of several genes. It shows central regulatory properties over Th17-cell development and is intensely upregulated within IBD-affected tissues. Here, we demonstrated that targeting Batf in IBD appears as a therapeutic approach that reduces colitogenic T-cell activities during fistula formation while aiming to affect inflammation in the gut epithelial cells.

Keywords: immune system, Crohn’s Disease, BATF, T helper cells, Bcl, interleukin, FOSL

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Authors: Carolyn Hatch, Laurent Simon

Abstract:

Urban mobility and the transportation industry are undergoing a transformation, shifting from an auto production-consumption model that has dominated since the early 20th century towards new forms of personal and shared multi-modality [1]. This is shaped by key forces such as climate change, which has induced a shift in production and consumption patterns and efforts to decarbonize and improve transport services through, for instance, the integration of vehicle automation, electrification and mobility sharing [2]. Advanced innovation practices and platforms for experimentation and validation of new mobility products and services that are increasingly complex and multi-stakeholder-oriented are shaping this new world of mobility. Transportation hubs – such as airports - are emblematic of these disruptive forces playing out in the mobility industry. Airports are emerging as the core of innovation ecosystems on and around contemporary mobility issues, and increasingly recognized as complex public/private nodes operating in many societal dimensions [3,4]. These include urban development, sustainability transitions, digital experimentation, customer experience, infrastructure development and data exploitation (for instance, airports generate massive and often untapped data flows, with significant potential for use, commercialization and social benefit). Yet airport innovation practices have not been well documented in the innovation literature. This paper addresses this gap by proposing a model of airport innovation that aims to equip airport stakeholders to respond to these new and complex innovation needs in practice. The methodology involves: 1 – a literature review bringing together key research and theory on airport innovation management, open innovation and innovation ecosystems in order to evaluate airport practices through an innovation lens; 2 – an international benchmarking of leading airports and their innovation practices, including such examples as Aéroports de Paris, Schipol in Amsterdam, Changi in Singapore, and others; and 3 – semi-structured interviews with airport managers on key aspects of organizational practice, facilitated through a close partnership with the Airport Council International (ACI), a major stakeholder in this research project. Preliminary results find that the most successful airports are those that have shifted to a multi-stakeholder, platform ecosystem model of innovation. The recent entrance of new actors in airports (Google, Amazon, Accor, Vinci, Airbnb and others) have forced the opening of organizational boundaries to share and exchange knowledge with a broader set of ecosystem players. This has also led to new forms of governance and intermediation by airport actors to connect complex, highly distributed knowledge, along with new kinds of inter-organizational collaboration, co-creation and collective ideation processes. Leading airports in the case study have demonstrated a unique capacity to force traditionally siloed activities to “think together”, “explore together” and “act together”, to share data, contribute expertise and pioneer new governance approaches and collaborative practices. In so doing, they have successfully integrated these many disruptive change pathways and forced their implementation and coordination towards innovative mobility outcomes, with positive societal, environmental and economic impacts. This research has implications for: 1 - innovation theory, 2 - urban and transport policy, and 3 - organizational practice - within the mobility industry and across the economy.

Keywords: airport management, ecosystem, innovation, mobility, platform, transport hubs

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Authors: F. Varga, Z. Liber, J. Jakše, A. Turudić, Z. Šatović, I. Radosavljević, N. Jeran, M. Grdiša

Abstract:

Dalmatian pyrethrum (Tanacetum cinerariifolium (Trevir.) Sch. Bip.; Asteraceae), a source of the commercially dominant plant insecticide pyrethrin, is a species endemic to the eastern Adriatic. Genetic diversity of T. cinerariifolium was previously studied using amplified fragment length polymorphism (AFLP) markers. However, microsatellite markers (single sequence repeats - SSRs) are more informative because they are codominant, highly polymorphic, locus-specific, and more reproducible, and thus are most often used to assess the genetic diversity of plant species. Dalmatian pyrethrum is an outcrossing diploid (2n = 18) whose large genome size and high repeatability have prevented the success of the traditional approach to SSR markers development. The advent of next-generation sequencing combined with the specifically developed method recently enabled the development of, to the author's best knowledge, the first set of SSRs for genomic characterization of Dalmatian pyrethrum, which is essential from the perspective of plant genetic resources conservation. To evaluate the effectiveness of the developed SSR markers in genetic differentiation of Dalmatian pyrethrum populations, a preliminary genetic diversity study was conducted on 30 individuals from three geographically distinct natural populations in Croatia (northern Adriatic island of Mali Lošinj, southern Adriatic island of Čiovo, and Mount Biokovo) based on 12 SSR loci. Analysis of molecular variance (AMOVA) by randomization test with 10,000 permutations was performed in Arlequin 3.5. The average number of alleles per locus, observed and expected heterozygosity, probability of deviations from Hardy-Weinberg equilibrium, and inbreeding coefficient was calculated using GENEPOP 4.4. Genetic distance based on the proportion of common alleles (DPSA) was calculated using MICROSAT. Cluster analysis using the neighbor-joining method with 1,000 bootstraps was performed with PHYLIP to generate a dendrogram. The results of the AMOVA analysis showed that the total SSR diversity was 23% within and 77% between the three populations. A slight deviation from Hardy-Weinberg equilibrium was observed in the Mali Lošinj population. Allele richness ranged from 2.92 to 3.92, with the highest number of private alleles observed in the Mali Lošinj population (17). The average observed DPSA between 30 individuals was 0.557. The highest DPSA (0.875) was observed between several pairs of Dalmatian pyrethrum individuals from the Mali Lošinj and Mt. Biokovo populations, and the lowest between two individuals from the Čiovo population. Neighbor-joining trees, based on DPSA, grouped individuals into clusters according to their population affiliation. The separation of Mt. Biokovo clade was supported (bootstrap value 58%), which is consistent with the previous study on AFLP markers, where isolated populations from Mt. Biokovo differed from the rest of the populations. The developed SSR markers are an effective tool for assessing the genetic diversity and structure of natural Dalmatian pyrethrum populations. These preliminary results are encouraging for a future comprehensive study with a larger sample size across the species' range. Combined with the biochemical data, these highly informative markers could help identify potential genotypes of interest for future development of breeding lines and cultivars that are both resistant to environmental stress and high in pyrethrins. Acknowledgment: This work has been supported by the Croatian Science Foundation under the project ‘Genetic background of Dalmatian pyrethrum (Tanacetum cinerariifolium /Trevir./ Sch. Bip.) insecticidal potential’- (PyrDiv) (IP-06-2016-9034) and by project KK.01.1.1.01.0005, Biodiversity and Molecular Plant Breeding, at the Centre of Excellence for Biodiversity and Molecular Plant Breeding (CoE CroP-BioDiv), Zagreb, Croatia.

Keywords: Asteraceae, genetic diversity, genomic SSRs, NGS, pyrethrum, Tanacetum cinerariifolium

Procedia PDF Downloads 114