Day 3 :
- Track : 17 Analytical Platforms in Metabolomics
Track : 19 Data Analysis & Systems Biology
Session Introduction
Kazuhiro Ogata
Yokohama City University Graduate School of Medicine, Japan
Title: Molecular Mechanism for modulationof a multiple transcriptionfactorcomplexformed on enhancer site upon phosphorylation
Time : 10:00-10:20
Biography:
K. Ogata has completed his PhD at the age of 27 years from Yokohama City University in 1992 and postdoctoral studies from RIKEN tsukuba institute. In 1997, He became the leader of the regulation of protein function project, Kanagawa Academy of Science and Technology (KAST), and from 2001,the professor and chair person of Department of Biochemistry, Yokohama City University Graduate School of Medicine.He has published papers in JMB, PNAS, NSMB, and Cell, and had been serving as an editorial board member of BBRC (2009-2010)
Abstract:
Transcriptional regulationis a fundamental mechanism for cell proliferation and differentiation. A major player in this process is a member of transcription factors (TFs).Activities of TFs are modulated by chemical modifications such as phosphorylation through cell signaling pathways directing cell functions. Molecular mechanisms of regulation for the functional high-order assemblyconsisting of multiple TFs and enhancer DNA (enhanceosome) under cellsignaling are largely unknown. So far, we investigated changes in assembly state of an enhance osome upon a TF’s phosphorylation, using crystallographical, biophysical, and molecular dynamic alanalyses. Here, wewill illustrate the case of Ets1 in non-phosphorylated and phosphorylated forms on its target gene enhancers with or withoutits partner TFs, Runx1/CBFï¢ or Pax5, as an example. A structure-function relationship of a TF-DNA assembly and an effect by phosphorylationwill be discussed.
Takeshi Kimura
Ajinomoto Co., Inc., Japan
Title: Development and commercialization of a plasma amino acid based risk diagnosis service
Time : 10:21-10:40
Biography:
Takeshi Kimura received his BSc in Cell and Molecular Biology and PhD in Biocheistry from University of London King’s Collage and became a Visiting Fellow and then Visiting Associate at LMB, NIDDK, NIH, Bethesda, MD, USA. He joined Ajinomoto Co., Inc. in 1989 and after heading the Washingto DC. Office, Basic Safety Research Group, Quality Assurance and External Scientific Affairs Department, R&D Planning Department., he became Member of the Board and Corporate Vice President in 2013. He is a Trustee for International Life Science Institute and Research Foundation, International Advisor to the Monell Chmical Senses Center amongst other external positions
Abstract:
From observations indicating that amino acids were a convenient metabolomic subset to investigate changes in metabolism associated with various physiological states, we have developed a technology package (“AminoIndex technology”) to generate biomarkers using plasma amino acid concentration data, and have commercialized a service based on this technology. In order to achieve commercialization, various problems ranging from sample handling, throughput, standardization and follow-up services had to be overcome and some of these issues, which may be relevant to other biomarker commercialization, will be addressed in the presentation. So far, “AminoIndex technology” has been used to generate risk biomarkers for gastric, lung, colorectal, prostate and breast cancer, and more recently for pancratic cancer, and since its launch as a biomarker service in April 2011 in Japan, it has been adopted by over 1000 hospitals and clinics as an optional blood test, and has led to the receipt of various awards in Japan. Research is ongoing to add other cancer risk biomarkers as well as biomarkers for other diseases risks and recent evidence indicate the possibility of generating biomarkers to predict the risk of developing a number of diseases four years in the future. We believe that in the near future, other validated metabolites and omics data could be added to the current analytical platform, increasing discriminative power. Although there are a number of issues still needing refinement, we believe that the “AminoIndex technology” platform can play a role in tailor-made nutrition and medicine.
Darby Tien-Hao Chang
National Cheng Kung University, Taiwan
Title: Studying Conformational Changes on GDP and GTP Binding with a Novel Visualization Platform
Time : 10:41-11:00
Biography:
Tien-Hao Chang received his B.S., M.S. and Ph.D. in Computer Science and Information Engineering from National Taiwan University. Currently he is a Professor of Department of Electrical Engineering, National Cheng Kung University. Dr. Chang focuses on machine learning and Systems Biology and has developed many analytical algorithms for protein/DNA sequences, structures, binding sites and interactions. He has co-worked with researchers in various fields such as computer science, life science, pharmacy and medicine and executed many cross-filed researches. Recently, he has expanded his interest and started to collaborate with specialists of industrial design, business, finance, data science and social science.
Abstract:
In many biological processes, proteins have important interactions with various molecules such as proteins, ions or ligands. Many proteins undergo conformational changes upon these interactions, where regions with large conformational changes are critical to the interactions. Several important proteins, such as the universal translation initiation factor (IF2/eIF5B), have been observed having large conformational changes on GDP and GTP binding. This work uses a novel platform, CCProf, to analyze conformational changes of entire proteins. This study analyzes protein conformational change with nine biological features, including potential binding target site, secondary structure, conservation, disorder propensity, hydropathy propensity, sequence domain, structural domain, phosphorylation site and catalytic site. All these information are integrated into a well-aligned view so that researchers can capture important relevance between different biological features visually. This analysis help researchers to study potential causes of conformational changes. The results of this work show two flexible regions with disorder-to-order transitions. The large conformational changes of these regions help to recognize multiple binding targets.
Jaleel Kareem Ahmed
Babylon University, Iraq
Title: Using chlorophyll as gamma absorber generated from uranium coated weapons to protect Iraqi children from cancer
Time : 11:01-11:20
Biography:
Jaleel Kareem Ahmed has completed his PhD from Baghdad University. He is the Dean of the Institute of Foundry and Hammering. He has registered 8 patents with 40 published papers and 3 books. He is a member in Who is Who network. He is a reviewer in Jon Wily and Sons and Editorial Board Member of Science Publishing Group and a member in Encyclopedia of Chemistry Scientists. He has got the Iraqi Scientist Medal. Currently, he is a Professor of physical chemistry in the College of Materials Engineering , Babylon University, Iraq.
Abstract:
Chlorophyll extracted from celery using 50% water – methyl alcohol as a solvent. By this method the concentration of chlorophyll (was 21% with yellowish-green color). This solution showed strongly absorption at 400 – 210 nm and maximum was at the end of ultra violet region. This absorption appeared in water, methyl alcohol, and acetone, but strongest absorption was in water. No emission spectra was detected in the ultra-violet region which means that chlorophyll absorbs radiation and dissipate it as a heat. Several samples of the above solution was irradiated by gamma ray from cesium-137 with energy of 0.7 Mev for different intervals ( 0.5, 1, 2, 4, 24 hours). The color of the solution disappeared after two hours radiation while the pH decreases from 6.38 for non-irradiated to 4.17 after 24 hours radiation with liberation of carbon dioxide which indicates destroying of chlorophyll but the absorption at 400 – 210 nm still exists which reflects the high stability of the group magnesium-four nitrogen atoms (tetrapyrrole) its energy about 3500 kJ mol-1. Calculation showed that the dosage of two hours radiation in which color of the solution disappeared (Compton effect) was 5.6 killogray (1 gray = 1 Joule per 1 kg sample) absorbed by chlorophyll before color disappear is enough to kills 1120 people weight 75 kg each within 14 days when the whole bodies exposure at one time. The glass containers and their plastic covers of the irradiated samples for 4 and 24 hours changed their color to violet may be due to the rearrangement of their physical structures. Others interesting points will appear in the full article. Capsules used as carrier for the chlorophyll to take it by children
Shrikant Mane
Yale University School of Medicine, USA
Title: Recent advancements in Mendelian genomics and data management at the Yale Center for Genome Analysis
Time : 09:55-10:20
Biography:
Shrikant Mane completed his PhD at The University of Bombay and Postdoctoral studies from The Johns Hopkins University School of Medicine. He is the Director of Yale Center for Genome Analysis, one of the most scientifically productive and accomplished Genome Centers. He has published more than 100 papers in reputed journals and has been serving as an ad hock reviewer of several journals. He is currently one of the principle investigators of a $12 million grant from NIH/NHGRI to establish The Yale Center for Genome Analysis
Abstract:
The Yale Center for Genome Analysis (YCGA) is a state-of-the-art DNA Sequencing Center launched in 2010 to provide an open access centralized facility for services, equipment and expertise required for carrying out large-scale sequence analysis studies. Since its inception in 2010, YCGA has emerged as one of the leaders in the field of identification of disease associated genetic factors. Our group foresaw scientific opportunities for the development and use of exome sequencing in Mendelian genetics and was the first to develop the method for exome capture on the Nimblegen/Roche platform. We were also the first to demonstrate the biological utility of exome sequencing for clinical diagnostic applications. Currently, YCGA is a part of the NHGRI supported Yale Center for Mendelian Genomics that uses NGS and computational approaches to discover the genes and variants that underlie Mendelian conditions. In the last four years, the use of next-gen sequencing has led to the publications of >200 articles in peer reviewed journals, including >40 in high profile journals such as Science, Nature, Cell, New England Journal of Medicine and Nature Genetics reporting new variants in various disorders, including hypertension, autism, several types of cancers, Gaucher disease, skin disorders, and cortical malfunctions, all using exome analysis. The presentation will focus on recent discoveries in Mendelian disorders made at YCGA, its computer infrastructure and the current challenges and solutions developed for data analysis and management.
Caihong Wei
Chinese Academy of Agricultural Sciences (CAAS), China
Title: Genome-wide analysis reveals population structure and selection in Chinese indigenous sheep breeds and reveals adaptation to high- altitude hypoxia in Tibetan sheep
Biography:
Caihong Wei has completed his PhD from Gansu Agrigultrural University. She is a key specialist of National Mutton Sheep Industry Technology System, a associated research fellow and a master tutor at the Chinese Academy of Agricultural Sciences (CAAS). She has published more than 16 papers in reputed journals and two monographs.
Abstract:
Traditionally, Chinese indigenous sheep were classified geographically and morphologically into three groups: Mongolian, Kazakh and Tibetan. Herein, we evaluate the population structure and genome selection among 140 individuals from ten representative Chinese indigenous sheep breeds: Ujimqin, Hu, Tong, Large-Tailed Han and Lop breed (Mongolian group); Duolang and Kazakh (Kazakh group); and Diqing, Plateau-type Tibetan, and Valley-type Tibetan breed (Tibetan group). We analyzed the population structure using principal component analysis (PCA), STRUCTURE and a Neighbor-Joining (NJ)-tree. In PCA plot, the Tibetan and Mongolian groups were clustered as expected; however, Duolang and Kazakh (Kazakh group) were segregated. STRUCTURE analyses suggested two subpopulations: one from North China (Kazakh and Mongolian groups) and the other from the Southwest (Tibetan group). In the NJ-tree, the Tibetan group formed an independent branch and the Kazakh and Mongolian groups were mixed. We then used the di statistic approach to reveal selection in Chinese indigenous sheep breeds. Among the 599 genome sequence windows analyzed, 16 (2.7%) exhibited signatures of selection in four or more breeds. We detected three strong selection windows involving three functional genes: RXFP2, PPP1CC and PDGFD. PDGFD, one of the four subfamilies of PDGF, which promotes proliferation and inhibits differentiation of preadipocytes, was significantly selected in fat type breeds by the Rsb (across pairs of populations) approach. Two consecutive selection regions in Duolang sheep were obviously different to other breeds. One region was in OAR2 including three genes (NPR2, SPAG8 and HINT2) the influence growth traits. The other region was in OAR 6 including four genes (PKD2, SPP1, MEPE, and IBSP) associated with a milk production quantitative trait locus. We also identified known candidate genes such as BMPR1B, MSRB3, and three genes (KIT, MC1R, and FRY) that influence lambing percentage, ear size and coat phenotypes, respectively. Tibetan sheep have lived at Tibetan plateau for thousands of years. They have adapted to the extreme environment of high altitude hypoxia through a long period of natural selection. Seven sheep breeds, can be clustered highland and lowland respectively, living at different area of China. FST and XP-EHH approaches were used to identify the regions harboring local positive selection between these two groups.We found 171 SNPs containing 152 genes with signals of positive selection in the highland sheep, with 21 of these candidate genes as being associated with high-altitude adaptation. Such as EPAS1, NF1, LONP1, DPP4, SOD1, PPARG, SOCS2 are involved in responses to hypoxia. Mutations of twelve are identified in exons at EPAS1, especially, one of which happened to a quite conserved site in the EPAS1 3’UTR domain. The relationship between blood-related phenotypes and EPAS1 genotypes on additional highland sheep at this loci reveals that the homozygous mutation is associated with the improved mean corpuscular hemoglobin concentration (MCHC) and mean corpuscular volume (MCV), which may help us to better understand physiological adaptability on Tibetan sheep. Taken together, our results not only provide the evidence on the genetic diversity of the highland sheep but also suggest potential mechanism for adaptation to hypoxia of high-altitude as well as the role of EPAS1 in the adaptive processes.
Yashwant Kumar Rao
GSVM Medical College, India
Title: Rapid analysis of hemoglobin variants in beta-thalassemia by HPLC in northern India
Biography:
Yashwant Kumar Rao has completed his MD from King George’s Medical University Lucknow UP, India. He is currently the Head of Department of Pediatrics GSVM Medical College Kanpur, a premier Medical institution of India. He has published more than 25 papers in reputed journals and has been serving as an Editorial Board Member of reputed journals.
Abstract:
Introduction: Beta-thalassemia is the most common and hereditary blood disorder worldwide, most of which are characterized by base substitution or small deletion or insertion of one or two nucleotides in the globin gene. Today due to the mixture of gene pool, this disorder is now not confined to any particular ethical group/races but each group represents its own sets of mutations. High Performance Liquid Chromatography forms a rapid, sensitive and precise method for detecting abnormal hemoglobin fractions. About 55 cases of Beta-thalassemia have been studied for various hemoglobin variants from Kanpur and adjoining areas. Material & Method: The study was performed on Agilent 1220 Infinity LC (Agilent Technologies) a High Performance Liquid Chromatography using EZChrom Elite for Beta-thalassemia. Result: Abnormal hemoglobin variants were analyzed for 55 cases of Beta-thalassemia on High Performance Liquid Chromatography. There were about 18 cases of Beta-thalassemia major and 37 cases of Beta-thalassemia carriers. The frequency observed in our study was HbA1c (0.14), HbF (0.7), HbE (0.45), HbD (0.34), HbS (0.45), and HbA2 (0.52). Conclusion: Automated High Performance Liquid Chromatography is an appropriate approach for the screening and presumptive identification of patients as well as carriers of Beta-thalassemia prior to DNA studies for definitive diagnosis.
Biography:
I have completed my M.SC. degree in medical Biochemistry since 2014 from Addis Ababa University,School of Medicine,department of Biochemistry and am working at Addis Ababa University,School of Medicine,department of Biochemistry as lecturer as well as as young researcher. I published three publication at reputable journals and doing research specially on Glycomics of Ethiopian society for biomarker of many types of cancers.
Abstract:
Glycomics refers to the broad study of complex carbohydrates, or glycans, in the form of oligosaccharide polymers, N- and O-linked glycoproteins, glycolipids, and proteoglycans. The process of adding these sugars to protein or lipid carriers is termed glycosylation. Normal physiological functions attributed to glycosylation include cellular mechanisms involving cell–cell adhesion, cell motility, inflammation, signal transduction, pathogen–host interactions, and viral entry. However, alterations to any of these processes can easily be linked to various ailments or oncogenesis and cancer progression, and similarly to other fundamental processes like embryogenesis, fertilization and stem cell differentiation. Glycomics composition and concentrations in human varies from individual to individuals since it depends on the food consumption habit, ethnicity, environmental factors and cultural diversity in continents or countries population. The aim of this study to analysis the Ethiopian normal population glycomics profile index which pave the way for new development glycomics-based clinically useful Cancer biomarker for early detection and therapeutic targets by using a variety of approaches and technologies. This research also requires extensive collaborations across institutions with different skills and facilities to accelerate glycan profile in Ethiopia which helps national cancer institute to detect and diagnose cancer at early stages. To complete this, we propose to evaluate the levels of normal glycoproteins in blood samples from healthy voluntary blood donors collected at Tikur Anbessa Specialized Hospital of Addis Ababa University (AAU), Ethiopia. Patients clinically suspected of any chronic diseases will be excluded. Blood drawn from consented normal adult persons (250 physiological persons) will be analyzed by glycobloating technologies both locally at AAU and abroad at Okayama University (Tokyo, Japan).
Mafalda Gomes
Centro Hospitalar do Porto Portugal
Title: About the Fetal Risks from Diagnostic use of Radiation during Pregnancy: a systematic review and proposal of a clinical protocol
Biography:
Mafalda Gomes has completed her Degree in Basic Health Sciences in the Faculty of Medicine of the University of Porto, the best Medical School in Portugal, in 2012. Engaged in one of the biggest Hospitals in the country, she gained clinical experience in Hospital S. João, with internships in Hospital Pedro Hispano and Póvoa de Varzim-Vila do Conde Hospital Center. In 2015 she finished her Master Degree in Medicine in the same Faculty of Medicine.
Abstract:
Aim: Analyze existing literature about the fetal risks of radiation exposure, producing a clinical protocol to guide radiation exposure in a clinical setting. Methods: An initial query was made on PubMed: “Diagnostic radiography in pregnancy AND radiation”, with the limits “published from January 1st 1993 to December 31st 2013, in English or Portuguese”. The articles that presented our aim were analyzed according to their MESH terms and created the final query: “((radiation) AND pregnancy) AND diagnostic imaging”. Research on April 15th of 2014, with the same limits, on PubMed gathered 688 articles; on SCOPUS 245 additional articles. After reading the title and abstract 298 articles remained. 179 allowed access to full text and were analyzed according to inclusion and exclusion criteria. A total of 103 articles were used and an additional one regarding In utero radiation exposure from atomic bombs. The PRISMA statement was followed. Results: Deterministic effects like pregnancy loss, congenital malformations, growth retardation and neurobehavioral abnormalities have threshold doses greater 100-200 mGy, being the risk considered negligible at 50 mGy. No diagnostic exam exceeds this limit. The most crucial time to avoid radiation exposure is from the 8th to the 15th week of gestation. The risk of carcinogenesis is slightly higher than the general population, although very similar. Intravenous contrast is discouraged, except in highly-selected patients. Conclusion: Measures to diminish radiation are essential and affect the fetal outcome. Nonionizing procedures should be considered whenever possible and every radiology center should have its own data on fetal radiation exposure.
Mohammad Reza Naghavi
University of Tehran, Iran
Title: Application of nano-particles in purification of pharmaceutical metabolites from plants
Time : 10:45-11:10
Biography:
Mohammad Reza Naghavi has completed his PhD from University of Tehran. He has published more than 130 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Abstract:
Pharmaceutical plant-derived metabolites such as Paclitaxel (Taxol), artemisinin, morphine, codeine, thebaine, etc are valuable plant-derived drugs showing activity against various human and animal diseases. Accordingly, the development of a more effective process for separation and purification of plant-derived metabolites is an important subject. Today, nano-structured materials are used in various fields including separation of materials in nanometer dimensions for water purification and chemical, food and pharmaceutical industry. The present research attempted to develop a new purification method using nano-particles, for mass production of plant-derived metabolites. The proficiency of a number of magnetic carbon-based nano-adsorbents was evaluated in pre-purification process of the crude paclitaxel extract obtained from fresh needles of yew tree (Taxus baccata L.). By considering decolorization efficiency, purity of taxol, recovery and reusability of adsorbents, Fe3O4Nps/GO (50 g/L) in dichloromethane was selected as the best medium for re-purification of paclitaxel. Our findings displayed promising applications of Fe3O4Nps/GO, as a cost effective nano-adsorbent, to provide a suitable vehicle toward improvement of paclitaxel pre-purification. This method was developed aiming at increasing yield and purity, also reducing solvent usage and the size and complexity of the HPLC operations for purification of metabolites.
- Special Session
Session Introduction
Eugenia Trushina
Mayo Clinic College of Medicine, USA
Title: Mitochondrial complex I as a target for neuroprotection
Time : 11:41-12:40
Biography:
Eugenia Trushina has completed her PhD from Saratov State University, Russia and Post-doctoral studies from Mayo Clinic College of Medicine, USA. She is an Associate Professor in the Departments of Neurology and Pharmacology at the Mayo Clinic Rochester, USA. Her scientific interests include the investigation of early molecular mechanisms of neurodegeneration, the role of mitochondria in particular. Translational aspect of her work includes the development of blood-based metabolic biomarkers and mitochondria-targeted small molecule therapeutics for Alzheimer’s disease. She is a recipient of the NIH, BrightFocus, GHR, ADDF, and Mayo Clinic Research Awards.
Abstract:
Neurodegenerative diseases are characterized by progressive neuronalloss that affects individuals’ cognitive and motor functions. Examples include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). Molecular mechanisms of neurodegeneration are not completely understood hindering the development of efficacious therapeutic treatments. The number of people living with dementia around the world is now estimated at 44 million, and is expected to rise to 76 million by 2030 and to 136 million by 2050. In the USA, AD currently affects more than 5 million Americans, with numbers expected to be 13.8 million by the year 2050. This is a terrible epidemic with no effective treatment and with multiple failed clinical trials focused on prevention of amyloid beta production. Alternative approaches are urgently needed. Despite different etiology of neurodegenerative diseases, they share some of the molecular mechanisms including protein aggregation, loss of mitochondrial function and increased oxidative stress. However, treatments with mitochondria-enhancing compounds or antioxidants did not provide a relief and failed clinical trials. In the recent years, a counterintuitive approach where a reduction of mitochondrial function using pharmacological inhibitors or genetic manipulations of the electron transport chain has been shown to induce positive cellular adaptation enhancing health and life span in model organisms and in humans. We demonstrated that mild inhibition of mitochondrial complex I with small molecules reduces levels of amyloid beta and phospho-Tau and averts cognitive decline in three preclinical animal models of AD. Modulation of complex I activity augmented mitochondrial bioenergetics increasing coupling efficiency of respiratory chain and neuronal resistance to oxidative stress. Metabolic signatures obtained in plasma and brain tissue of AD mice treated with these small molecules allowed monitoring target engagement and confirms the proposed mechanism. I will discuss current stage of the development of mitochondria-targeted small molecule-based therapeutics, progress in the understanding of the molecular mechanism, and strategies for successful translation of this approach to humans.