8th International Symposium on OMICS and...

8th International Symposium on OMICS

and Bioinformatics

September 17 to 20, 2018

Melia Marina Varadero Hotel, Cuba

Index OPENING SESSION ...................................................................................................... 1

Monday September, 17th ...................................................................................... 1

ORAL PRESENTATIONS ................................................................................................ 2

Tuesday September, 18th ....................................................................................... 2

Wednesday, September 19th ................................................................................ 4

Thursday, September 20th ...................................................................................... 6

ORAL SESSION ABSTRACTS ......................................................................................... 7

Integration and translation of “omics technologies” to develop personalized

medicine ................................................................................................................ 9

TB or not TB: New metabolomics biomarkers better characterizing and

diagnosing tuberculosis. ...................................................................................... 11

Advances and Challenges of Single Cell RNA Sequencing Data Analysis .............. 14

Natural antisense transcripts, physiological roles and potential biomedical

applications .......................................................................................................... 15

Past and present of laser capture microdissection application in intracardiac

nervous system research ..................................................................................... 16

Imaging mass spectrometry and microbial metabolomics on track of infectious

diseases ................................................................................................................ 17

Ambient ionization mass spectrometry in bioanalysis ......................................... 19

Advanced molecular tools for parallel protein analyses, imaging and diagnostics

............................................................................................................................. 20

Personalised Medicine: the Application of Genomics to Health Care ................. 21

Novel Atxn2-CAG100-KnockIn mice as model of Spinocerebellar Ataxia type 2 .. 22

Metabolome and lipid profile of SCA2 brain tissue in Atxn2-CAG100-KnockIn

mice and in a patient ........................................................................................... 23

Modulation of genes for the combination phycocyanobilin and ifn beta promises

greater expectations for a new therapy for multiple sclerosis ............................ 25

HLA alleles and TNF promotor genes polymorphism among Cuban patients group

with MS and NMO................................................................................................ 27

Assessment of variants in the huge Titin gene - NGS results in 2700 myopathy

patients ................................................................................................................ 29

Global analysis of genes expression regulation by the antitumor peptide CIGB-

300 in acute myeloid leukemia cell lines ............................................................. 32

Variety of proteoforms in cancer cells ................................................................. 33

Nutriepigenomics in Cancer Development .......................................................... 35

POSTER SESSION ....................................................................................................... 36

POSTER SESSION ABSTRACTS .................................................................................... 40

Pilot study: Study of utility of depressive symptom screening through

measurement of saliva biomarker ....................................................................... 42

Decreased Quality of life in Elderly Patients with Subsyndromal Depression ..... 44

Salivary cortisol level in sleep-disordered breathing patients ............................. 46

Antidepressants and Mood Stabilizers: Novel Research Avenues and Clinical

Insights for Bipolar Depression. ........................................................................... 48

Associations between immune activation and the current severity of the "with

anxious distress" specifier in patients with depressive disorders ........................ 50

There is a correlation between plasma erythropoietin levels and attention deficit

hyperactivity disorder symptoms ........................................................................ 52

Plasma glial-derived neurotrophic factor in attention deficit hyperactivity

disorder ................................................................................................................ 54

Korean Medication Algorithm for Bipolar Disorder: changes in preferred

medications for mania over 16 years ................................................................... 56

Association Study between Amisulpride Treatment Response and Dopamine D3

Receptor Gene Polymorphisms in schizophrenic patients ................................... 58

Effects of LY341495 on the dendritic outgrowth and spine formation in the rat

hippocampal neuron under toxic condition ......................................................... 60

Association between glycogen synthase kinase-3β gene polymorphisms and

attention deficit hyperactivity disorder in Korean children: A preliminary study 62

A case-control association study of serotonin 1A receptor gene and tryptophan

hydroxylase 2 gene in attention deficit hyperactivity disorder. ........................... 64

Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children

with attention deficit-hyperactivity disorder (ADHD) .......................................... 66

Liraglutide activates mTORC1 signaling and AMPA receptors in rat hippocampal

neurons under toxic conditions ........................................................................... 67

Interaction of TNF-alpha (-308 GA) polymorphism and HLA-DRB1/DQA1 alleles

associated with susceptibility to multiple sclerosis. ............................................ 69

Comparative study of gene expression in the colon of rat biomodel with

ulcerative colitis, treated or not with Pellet-EGF. ................................................ 71

Expression profile of genes related to apoptosis in the colon of rats with

ulcerative colitis treated with EGF ....................................................................... 73

Identification of the reference materials proteins from Saccharomyces cerevisiae

by 2DE and Mass Spectrometry ........................................................................... 74

Characterization of low‐abundance species in the active pharmaceutical

ingredient of a synthetic peptide CIGB‐300 ......................................................... 75

Targeting protein hydrophilic regions by MS via in-solution buffer-free trypsin

digestion .............................................................................................................. 76

In Silico Assessment of Potential Druggable Pockets on the Surface of

Nucleophosmin .................................................................................................... 77

In silico analysis of the interaction between the HLA II receptor associated with

Reumetoid Arthritis and altered peptide ligand. ................................................. 78

Impact of post-translational modifications on signaling pathways in patients with

lung cancer ........................................................................................................... 79

CIMABior® a cuban human anti-CD20 monoclonal antibody to patients with

indolent non-Hodgkin lymphoma. ........................... ¡Error! Marcador no definido.

HLA alleles and TNF promotor genes polymorphism among Cuban patients group

with MS and NMO.................................................... ¡Error! Marcador no definido.

Analysis of post-translational modifications in Acute Myeloid Leukemia and their

impact in the discovery of new biomarkers. ........................................................ 80

Mass Spectrometric analysis and biological activity of Bm86-pP0: A peptide-

conjugated vaccine candidate against ticks ............. ¡Error! Marcador no definido.

PARTICIPANTS LIST.................................................................................................... 82

Convention Center Maps .......................................................................................... 90

OPENING SESSION (Hicacos II room)

Monday September, 17th

18:00-18:15 Welcome remarks:

Dr. Silvio Perea, Cuba (Center for Genetic

Engineering and Biotechnology, Havana, Cuba)

18:15-19:00 Opening lecture:

Dr. Gerardo Guillén (Director of Biomedical

Research at CIGB, Cuba)

19:00-20:00 “GET-TOGETHER WELLCOME COCKTAIL

(Marine Boulevars)

ORAL PRESENTATIONS

Tuesday September, 18th

Integration of OMICs in Biomarker discovery and Personalized

Medicines

(Hicacos II room)

Chairpersons: Prof. Kewal K. Jain (Switzerland) and Dr. Luis

Javier González (Cuba)

8:30-9:15 Key Lecture:

Prof. Kewal K. Jain (Switzerland)

Integration and translation of OMICs technologies

(genomics, proteomis, metabolomics, etc) using systems

biology approach to develop personalized medicines (from

discovery to clinical applications).

9:30-9:55 Prof. Du Toit Loots, South Africa

TB or not TB: New metabolomics biomarkers better

characterizing and diagnosing tuberculosis.

10:00-10:25 Dr. Beatriz Mancheco Teruel, Cuba

Cuba: the history of admixture and population structure

using genome-wide data.

10:30-10:55 Dr. Susmita Datta, USA

Advances and Challenges of Single Cell RNA Sequencing

Data Analysis.

11:00-11:15

11:15-11:40

Dr. Andreas Werner, UK

Natural antisense transcripts, physiological roles and

potential biomedical applications.

11:45-12:10 Dr. Chottova Dvorakova M, Czech Republic

Past and present of laser capture microdissection

application in intracardiac nervous system research.

12:15-12:40 Dr. Vladimir Havlicek, Czech Republic

Imaging mass spectrometry and microbial metabolomics on

track of infectious diseases.

12:35-01:05 Dr. Karel Lemr, Czech Republic

Ambient ionization mass spectrometry in bioanalysis.

1:15-1:40 Dr. Masood Kamali Moghaddam, Sweden

Advanced Molecular Tools for Proteome Analyses and

Diagnostics

1:40-2:40

2:45-17:00 POSTER SESSION

Wednesday, September 19th Biomarkers and Drugs in Ataxia and in Others Neurodegenerative

Diseases

(Hicacos II room)

Chairpersons: Prof. Georg Auburger (Germany) and Prof. Luis

Velázquez Pérez (Cuba)

8:30-9:15 Key lecture:

Prof. Robert Williamson, Australia

Personalised Medicine: the Application of Genomics to

Health Care.

9:30-9:55 Prof. Luis Velázquez Pérez, Cuba

Biomarkers, Precision Medicine and early intervention in

Spinocerebellar Ataxias.

10:00-10:25 Dr. Suzana Gispert Sanchez, Germany

Novel Atxn2-CAG100-KnockIn mice as model of

Spinocerebellar Ataxia type 2

10:30-10:55 Prof. Georg Auburger, Germany

Metabolome and lipid profile of SCA2 brain tissue in Atxn2-

CAG100-KnockIn mice and in a patien

11:00-11:15

11:15-11:40 Dr. Luis Almaguer Mederos, Cuba Massive analysis of cDNA ends applications to ataxin-2

knockout mice.

11:45-12:10 Dr. Giselle Pentón-Rol, Cuba Modulation of genes for the combination phycocyanobilin

and ifn beta promises greater expectations for a new

therapy for multiple sclerosis.

12:15-12:40 Dr. María Elena Fernández de Cossio, Cuba

HLA alleles and TNF promotor genes polymorphism among

Cuban patients group with MS and NMO.

12:45-13:10 Prof. Bjarne Udd, Finland

Assessment of variants in the huge Titin gene - NGS results

in 2700 myopathy patients

13:10-15:00

15:00 FREE TIME

Thursday, September 20th Drug Development and Biomarker Discovery in Cancer

(Hicacos II room)

Chairpersons: Dr. J. Kevin Hicks (USA) and Dr. Julio R Fernandez

(Cuba)

08:30-09:15 Key lecture: Dr. J. Kevin Hicks, USA Implementation of genomic medicine to guide drug selection and mitigate risks

9:30-9:55 Dr. Dania M. Vázquez, Cuba

Global analysis of gene expression regulation by anti-

tumor peptide CIGB300 in acute myeloid leukemia cell

lines.

10:00-10:25 Dr. Stanislav N. Naryzhny, Russia

Variety of proteoforms in cancer cells.

10:30-10:55 Prof. Mihalis I. Panagiotidis (UK)

Nutriepigenomics: The role of natural products in

epigenetic control of human carcinogenesist.

11:00-11:30 Closing remark, closing toast and official group

pictures

(Main Convention Center aisle)

ORAL SESSION ABSTRACTS

Integration and translation of “omics technologies” to develop

personalized medicine

K. K. Jain MD, FRCSC, FRACS, FFPM CEO, Jain PharmaBiotech, Basel, Switzerland.

jain@pharmabiotech.ch

Personalized medicine, the prescription of specific therapeutics best suited for an individual taking into consideration both genetic, epigenetic, and environmental factors that influence response to therapy. Among the many synonyms, both genomic medicine and precision medicine are inadequate for indicating the global impact of personalized medicine, which is the best concept to integrate various ‘omics’ and ‘non-omics’ technologies for translation into optimal healthcare for patients. Systems biology can facilitate the development of personalized medicine by identification of the biological networks associated with the disease and response to therapy. Systems biology concept has been applied to other sciences relevant to personalized medicine: systems pathophysiology of diseases and systems pharmacology. Molecular diagnostics, molecular imaging, sequencing, and monitoring of gene expression by microarrays are important technologies for this purpose. Besides omics, e.g., pharmacogenomics and pharmacoproteomics, nongenomic technologies such as nanobiotechnology are also used. Biological therapies for neurological disorders, such as cell therapy, gene therapy, gene editing, RNAi, vaccines and monoclonal antibodies can also be personalized. Synthetic biology is also contributing to personalized medicine. Biomarkers and integration of diagnostics with therapeutics are important for the selection and monitoring of treatments. Biomarkers enable presymptomatic diagnosis, selection of appropriate treatment, assessment of disease progression, and evaluation of patient response to therapy. Nanobiotechnology has refined molecular diagnosis, improved drug formulation and targeted delivery through the blood-brain barrier to the lesion in the brain and spare the normal tissues to reduce systemic toxicity. Integration of multiple factors into personalized approach requires use of bioinformatics.

Advantages and future of personalized medicine are:

The availability of low-cost genomic sequencing will expand the use of genomic information in the practice of medicine.

Sequencing of the genome is enabling genetic redefinition of several diseases as well as better insight into their pathomechanisms to improve our understanding and facilitate early detection by molecular methods.

An increase in the ability to anticipate diseases rather than just reacting to them after onset may enable the institution of preventive measures.

The precision and effectiveness of drugs is increased.

Reduction of adverse effects of drugs.

Drugs can be better targeted to diseases in some patients based on genotype information.

TB or not TB: New metabolomics biomarkers better characterizing

and diagnosing tuberculosis.

Du Toit Loots Human Metabolomics, North-West University, Potchefstroom South Africa.

dutoit.loots@nwu.ac.za

Statement of the Problem: Despite the fervent genomic and proteomic based research efforts to date, since its discovery in 1882, TB is still a major global problem, and hence new approaches are necessary to better characterize and diagnose this disease. One such a strategy would be to investigate this from a metabolomics research perspective, in order to identify new metabolite markers better characterizing the disease. Methodology & Theoretical Orientation: A typical metabolomics workflow, including using semi-targeted and untargeted extraction procedures on cell cultures and patient collected sputum and urine, analysis on various LC-MS, GC-MS and NMR based approaches, followed by data clean-up and biomarker identification using various univariate and multivariate statistical approaches, was applied. Findings: The new TB biomarkers identified in the different sample material shed light on new metabolic pathways and mechanisms associated with growth, virulence, drug resistance, host and microbe interactions/adaptations, improved diagnostics and predicting treatment outcome. Conclusion & Significance: Over the past 10 years, metabolomics has led to an exponentially increased number of new biomarkers identified, and subsequently rapid expansion of new knowledge and our understanding of various infectious diseases, including TB, which can ultimately be utilized towards improved diagnostics and treatment approaches.

Cuba: the history of admixture and population structure using

genome-wide data.

Beatriz Mancheco

beatriz@infomed.sld.cu

Cuban people pose one of the most complex “genetic crucibles” in the world, driven by a heterogeneous heritage. Cuba has a high degree of three-way admixture: Native Americans, Africans and Europeans. This complex mixture is an ideal venue to understand the impact of historical and social factors on modern genetic patterns and its relationship with health and diseases. The present study was aimed to explore Cuba’s population structure and demographic history, by using a dense genome-wide SNP dataset of 957 individuals. Based on both bayesian clustering and haplotype-based methods, we describe genetic diversity patterns in the present-day Cuban population. We then evaluate whether there are differences in patterns of sex-specific admixture in Cuba. As result of our study we concluded that Cuba has experienced major demographic migrations involving multiple indigenous groups, European settlers, and enslaved Africans, as well as recent intracontinental large-scale population movements in the Americas. The present-day Cuban population has genetic differences with other Hispanic/Latino populations, and there is also evidence of population structure across the island. European ancestry is higher in Western than in Eastern provinces, except for Havana. The Eastern provinces of Granma, Las Tunas, and Holguin show the highest Native American ancestral proportions and our Identical By Descent analysis shows that these three provinces share recent common ancestors at much higher rates than any other Cuban province. In contrast, the Eastern provinces of Santiago de Cuba and Guantanamo have the highest African ancestral proportions observed in Cuba. One of the major strengths of this study is that the analysed Cuban dataset captures the demographic

characteristics of the Cuban population in terms of population density, age, and gender.

Advances and Challenges of Single Cell RNA Sequencing Data

Analysis

Susmita Datta Professor, Co-Director of Biostatistics and Epidemiology Research Design (CTSI);

Tenured Professor and Preeminent Hire Department of Biostatistics; College of Public Health & Health Professions and College of Medicine

University of Florida

susmita.datta@ufl.edu In usual bulk RNA-seq study one can only observe mRNA expression averaged over thousands of cells, which can seriously mask the signal of interest due to cell population heterogeneity. Opposed to that Single cell RNA sequencing is a much improved platform where the data can provide an unprecedented resolution. With this platform one can observe the mRNA expression at every cellular level. However, scRNA-seq data, unlike transcriptomic data from bulk RNA sequencing, contain many zero signals, high variability and multiple modes. Consequently, using the computational approaches to analyze unimodal bulk RNA-seq data may not be appropriate for the analysis of scRNA-seq data to realize its fullest potential. In this talk, we will provide a brief description of the existing methods, thus far for the analysis of scRNA-seq data. Additionally, we will present a novel statistical model for high dimensional and zero-inflated scRNA-seq count data to identify differentially expressed genes across cell types in case control study. We apply our proposed methodology to both simulated and real data and compare the results to other popular methods designed for detecting differentially expressed genes.

Natural antisense transcripts, physiological roles and potential

biomedical applications Andreas Werner

Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne, United Kingdom

andreas.werner@newcastle.ac.uk Large proportions of the human genome do not code for proteins and were long

considered as junk or ‘the dark matter of the genome’. Recent studies, however,

show that transcription occurs in noncoding regions and also in the opposite

direction of protein coding genes. The resulting noncoding RNAs have emerged as

essential and abundant regulators of eukaryotic gene expression. The physiological

importance of the novel regulators is substantiated by diseases -including cancer,

Alzheimer’s and thalassemia- that may be caused by missing or over-expressed

noncoding RNAs. Many details of how noncoding RNAs regulate gene expression

are currently unknown and these problems are intensely investigated in biomedical

research.

Our interest focuses on a particular family of noncoding RNAs, so-called natural

antisense transcripts. Natural antisense transcripts are long regulatory RNAs that

are transcribed in the opposite direction of protein-coding transcripts and

potentially regulate their expression level. Genome wide studies suggest that

natural antisense transcripts play an important role during sperm development and

are hypothesised to enable the evolution of complex organisms. On the other hand,

natural antisense transcripts offer novel targets to modulate the expression of

protein coding genes using genome editing tools.

Past and present of laser capture microdissection application in

intracardiac nervous system research

Magdalena Chottova Dvorakova Dpt. of Physiology, and Biomedical Center, Faculty of Medicine in Pilsen, Charles

University, Czech Republic

Magdalena.dvorakova@lfp.cuni.cz Laser capture microdissection (LCM) is an excellent method which enables to

prepare pure cell population sample from heterogeneous tissue section or cell

culture. Subsequent application of genomic and proteomic methods allows

determination of gene and protein expression specific for tested cells, which is very

useful tool in basic science. Compared to cultured cells, microdissected cells display

very different genetic profile suggesting importance of analysis of cells from their

natural environment. Additionally, reaction of selected cell types to physiologic

and/or pathophysiologic conditions could be studied with high accuracy.

Nerve cell bodies of intracardiac nervous system are localized mainly within the

atrial wall in the rat. In order to analyze expression of members of different

neuropeptide signaling systems, LCM is very good way how to obtain samples

containing nervous tissue or just nerve cell bodies.

Imaging mass spectrometry and microbial metabolomics on track

of infectious diseases

Vladimir Havlicek PhD, "Institute of Microbiology, Prague", Czech Republic

vlhavlic@biomed.cas.cz

Introduction

Mixed infections represent a diagnostic challenge for any microbiology laboratory.

In this work, high mass resolution spectrometry is introduced as extremely sensitive

tool for early detection of Aspergillus and Pseudomonas infections in rat models.

Microbial siderophores were used as specific disease biomarkers and detected in

urine, serum and tissues of infected animals.

Methods and Results

Using a model of experimental aspergillosis in Lewis rats, the fungal siderophores

ferricrocin (FC) and triacetylfusarinine C (TAFC) were identified as markers of

Aspergillus fumigatus infection. Analogously, bacterial pyoverdine E (PyE) was

quantified in urine, serum and lung tissues in rats infected with Pseudomonas

aeruginosa. Molecular biomarkers were analyzed by matrix-assisted laser

desorption ionization (MALDI) or electrospray ionization (ESI) using a 12T SolariX

Fourier transform ion cyclotron resonance (FTICR) mass spectrometer (MS). Non-

invasive diagnoses were performed with animal urine. MS imaging (MSI)

experiments on tissues and liquid chromatography (LC)-ESI analyses of rat sera

represented the invasive armories.

Results

In experimental aspergillosis, the mean concentrations of TAFC and FC in the

infected rat urine were 0.37 and 0.63 μg/mL, respectively. The limits of detection of

the ferri-forms of TAFC and FC in the rat urine were 0.02 and 0.03 ng/mL,

respectively. As an example, the initial FC signal in urine reflecting the infection

appeared two days post-infection. The MALDI FTICR MSI illustrated the actual

microbial ferricrocin

distribution in the lung tissue and resolved the false-positive results obtained by the

light microscopy and histological staining. In an analogous experiment with

Pseudomonas aeruginosa, PyE was quantified in rat urine by LC-FTICR approach by

application of PyE non-isobaric analogues. Separation of desferri and ferriforms of

siderophores was achieved on biphenyl LC column. In parallel, PyE was visualized by

MALDI-MSI in infected lung and muscle tissues. Lateral distribution of PyE

correlated with bacterial bodies visualized by scanning electron microscopy.

Innovative aspects

• Ferricrocin and triacetylfusarinine C were identified, quantified and visualized as

biomarkers of Aspergilus fumigatus infection with LC-MS and MALDI-MSI approach

respectively.

• Pseudomonas aeruginosa infection in lung tissue was visualized by MALDI mass

spectrometry imaging and scanning electron microscopy

• Proper alignment of various images (mass spectrometric, microscopic) was

accomplished by our in-house software called CycloBranch

Acknowledgement

Ministry of Education, Youth and Sports of the Czech Republic (NPU LO1509) and

Czech science Foundation (16-20229S).

Ambient ionization mass spectrometry in bioanalysis

Lemr, K.,1 Borovcová, L.,1 Fryčák, P.,1 Havlíček, V.2

1Department of Analytical Chemistry-RCPTM, Faculty of Science, Palacky University, 17. listopadu 12, 771 46 Olomouc, Czech Republic

2Laboratory of Molecular Structure Characterization, Institute of Microbiology ASCR, v.v.i., Videnska 1083, 142 20 Prague 4, Czech Republic

Karel.Lemr@upol.cz Since introduction of ambient ionization in 2004 different techniques have been

described, including desorption nanoelectrospray developed in our laboratory. It is

usually said that these techniques require no or minimal sample preparation. More

precisely sampling as liquid extraction, laser ablation or thermal desorption occurs

during process of ionization. Limited sample preparation can cause lower sensitivity

sometimes but can also allow rapid analysis in real time. Combination of ambient

ionization with a portable miniature mass spectrometer allows on-site analysis. In

bioanalysis, many interesting applications can be found in the literature. For

example ambient ionization techniques have been applied to screening of drugs of

abuse in urine or dried blood spot analysis discriminating enantiomers of

pharmaceuticals. Single cell analysis was performed by mid infrared laser ablation

of cell content. Ambient ionization techniques can provide mass spectrometry

images of tissue sections revealing e.g. distribution of lipids in a mouse brain. In vivo

tissue characterization by rapid evaporative ionization mass spectrometry is

another fascinating medical application that might help to surgeons in the future.

The authors gratefully acknowledge the support from ERDF/ESF “Nano4Future"

(project CZ.02.1.01/0.0/0.0/16_019/0000754) and the Ministry of Education, Youth

and Sports of the Czech Republic (project LO1305).

Advanced molecular tools for parallel protein analyses, imaging

and diagnostics

Kamali-Moghaddam M, Manoucheheri E, Gallini R, Azimi A, Wu D Dept. of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala

University, Uppsala, Sweden

masood.kamali@igp.uu.se Despite a large number of protein biomarker candidates presented in the literature,

only a small group of proteins have been demonstrated to be clinically useful.

Identification of reliable biomarkers in the biological samples requires access to

technologies with sufficient specificity and sensitivity to meet the complexity of, for

instance, blood proteomic. In addition, the focus on proteins as biomarker has now

being expanded to other biomolecules such as high molecular weight microvesicles

and exosomes. We have developed a large number of molecular tools such as the

proximity assays using sets of antibodies with conjugated DNA strands for single

and parallel measurements of proteins in cells, tissue sections and body fluids to

improve the detection of proteins, their interactions and modifications, in research

and for routine diagnostics. In these technologies the extreme specificity and

sensitivity of target molecule detection result from the requirement of multiple

recognition events, combined with high efficiency of signal detection due to

amplification of DNA molecules that form in the detection reactions. The multi

recognition of each target molecule also allows parallel analyses of panels of

proteins in minute sample aliquots, while the DNA assisted readout avoids

problems with cross-reactivity upon multiplexing. Here, I discuss the methodologies

and illustrate applications of these technologies for detection of biomolecules, and

screening and validation of protein biomarkers in diseases such as cancer,

neurodegenerative and autoimmune disorders, and the use of multiplex proximity

assays for detection and characterization of high-order protein complexes – such as

microvesicles – as biomarkers.

Personalised Medicine: the Application of Genomics to Health Care

Robert Williamson FRS, Honorary Senior Principal Research Fellow, Murdoch Childrens Research

Institute and University of Melbourne

r.williamson@unimelb.edu.au Advances in genomics, combined with the application of advanced computing

technology and artificial intelligence to population data, leads to a new concept of

medicine, where risk can be assessed before a person becomes sick. This means

that national resources can be used to preserve health rather than treat illness.

This approach not only requires the ethical use of information from genetic and

genomic data from many individuals, but also will shift responsibility for health (at

least in part) from the doctor to the healthy citizen. This will be of particular

importance when attempting to prevent neurodegenerative diseases of the elderly

for which risk can be predicted, such as dementia. Australia, like Cuba, has a

national health care system which is, for the most part, paid for by the government,

but there are still many obstacles that have to be overcome before personalized

medicine can be applied successfully.

Novel Atxn2-CAG100-KnockIn mice as model of Spinocerebellar

Ataxia type 2

Gispert S1, Halbach M1, Sen NE1, Canet-Pons J1, Auburger G

1Experimental Neurology, Goethe University Medical School, 60590 Frankfurt am Main, Germany.

gispert-sanchez@em.uni-frankfurt.de Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative

disease caused by the unstable expansion of a polyglutamine (polyQ) repeat in the

RNA-binding starvation factor Ataxin-2. Conversely, deficiency of Ataxin-2 has

neuroprotective effects for the motor neuron diseases ALS and FTLD and for

Spinocerebellar Ataxia type 1. We generated a novel genetic mouse model of SCA2

via KnockIn of a CAG100 repeat into the murine Atxn2 gene. The repeat is unstable

in somatic cells and expands over successive generations. Body and brain weight

decrease to about 50% before death around 14 months of age. Motor deficits start

with limited grip strength at the age of 7 months, evolve to impair rotarod

performance by 12 months and make spontaneous vertical movements in open

field impossible. The detection of cytosolic inclusion bodies containing the protein

Ataxin-2 reveals the typical neurodegeneration pattern of spinal motor neurons,

inferior olivary nucleus, pontine nucleus and cerebellar Purkinje neurons found in

patients. Neuron loss was not prominent at maximal age, but affection of

myelinated axons and perineuronal nets caused a disconnection of cell contacts in

the central nervous system. Global OMICS at the protein level and at the mRNA

level identified underlying defects in the mitochondrial homeostasis of glucose,

amino acids and fatty acids.

Metabolome and lipid profile of SCA2 brain tissue in Atxn2-

CAG100-KnockIn mice and in a patient

Auburger G1, Meierhofer D2, Sandhoff K3

1 Exp. Neurology, Goethe University Frankfurt am Main;

2 Max Planck Institute for Molecular Genetics, Berlin; 3 Kekulé Institute for Organic Chemistry and Biochemistry, University Bonn,

Germany.

auburger@em.uni-frankfurt.de Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative

disease caused by the unstable expansion of a polyglutamine (polyQ) repeat in the

RNA-binding starvation factor Ataxin-2, which modulates lipid and glucose

breakdown in mitochondria via mTORC1 signaling. Conversely, deficiency of Ataxin-

2 has neuroprotective effects for the motor neuron diseases ALS and FTLD, for

Spinocerebellar Ataxia type 1, and possibly also for Parkinson’s disease.

Having generated a novel genetic mouse model of SCA2 via KnockIn of a CAG100

repeat into the murine Atxn2 gene and having demonstrated that it mimicks the

selective motor deficits, the spatial neurodegeneration pattern and the subcellular

hallmarks known from SCA2 patients, we analyzed the global metabolome profile of

cerebellum and spinal cord.

The findings were consistent between both tissues and revealed prominent down-

and up-regulations of membrane lipids in this mouse model, consistent with the

strong demyelination that was demonstrated upon histological stains. Interestingly,

the data suggest that lipid signals within neuronal excitability are altered even more

than the structural lipids. The analysis of a SCA2 patient brain with thin layer

chromatography also detected dysregulations of the same structural lipids as a

correlate of demyelination. We conducted expression analyses to identify the lipid

homeostasis enzymes that are responsible for these dysregulations.

Overall, Ataxin-2 appears to modulate not only the fat reserves in the liver and the

subcutaneous tissue, as previously published, but to have also profound effects on

brain myelin lipids.

Modulation of genes for the combination phycocyanobilin and ifn

beta promises greater expectations for a new therapy for multiple

sclerosis

G Pentón-Rol 1, N Pavón-Fuentes 2, J Marín-Prida 3, M Cervantes-Llanos 1, H Camacho- Rodriguez 1, B Piniella-Matamoros 1, JR Fernandez-Massó 1, MM Teixeira4

1 Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/ 158 y 190,

Cubanacán, Playa, Havana, PO Box 6162, Cuba 2 International Center for Neurological Restoration (CIREN), Ave. 25 e/ 158 y 160,

Playa, Havana, PO Box 11300, Cuba 3 Center for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and

Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, Havana, PO Box 430, Cuba 4 Laboratory of Immunopharmacology, Department of Biochemistry and

Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, Brazil

giselle.penton@cigb.edu.cu Introduction: Multiple sclerosis (MS) is leading causes of neurological disability among adults. We have evaluated the effect of combination Phycocyanobilin (PCB) and IFN beta (PCB/IFNb) on genes modulation related to the events of MS pathogenic mechanism such as: demyelination, immunomodulation and oxidative stress in animal models of MS (EAE). Material and Methods: EAE was induced in C57BL6 mice with MOG peptide. PCB was administered by oral route daily and IFN Beta subcutaneously every second day. Total RNA from brain was extracted and the expression of the genes LINGO1, CXCL12 (demyelinating/remyelinating processes), Tbet, GATA3, RORg, Foxp3 (effector/regulator balance) and Hmox1 and Nfr2 (oxidative stress) were evaluated by Real-time-quantitative-PCR (qPCR). Furthermore, we screened spleens for regulatory T cell subset modulation/induction using flow cytometry Results: There was an effect of combination PCB/IFNb demonstrated by a downregulation of the genes linked to demyelination and an upregulation of genes

involved in remyelination. The ratio CXCL12/LINGO1 was upregulated. The genes for the transcriptional factors GATA3 and RORg were downregulated only by o after the treatment of PCB/IFNb combination; a similar regulation was observed for the Hmox1 gene. Moreover, an induction of regulatory T cells in the spleen of combination treated animals of EAE model was verified by flow cytometry. Conclusion: The genes evaluated are currently the most important within the most novel pathways and targets for MS research and can support the link between Treg and remyelination in MS.

HLA alleles and TNF promotor genes polymorphism among Cuban

patients group with MS and NMO.

Fernández-de-Cossío, ME1*, Cintado, A1*, Nazabal M1, Camacho H1*, Díaz T1, Villarreal A1, Ale M1, Grass D2, Cervantes-Llanos M1, Pavon-Fuentes N2, Benitez JV1,

Cabrera-Gomez JA2, Diaz de la Fe A2, Pentón-Rol G1

1Pharmacogenomics Department. Biomedical Research Division. Center for Genetic Engineering and Biotechnology, 31 entre 158 & 190, Cubanacán, Playa, Cuba.

2International Center of Neurological Restoration. Ave 25 no 15805 entre 158 & 160 Cubanacan Playa, Cuba.

mariaelena.fernandez@cigb.edu.cu Multiple sclerosis (MS) and Neuromyelitis optica (NMO) are inflammatory,

demyelinating, autoimmune diseases of the central nervous system (CNS). These

two disorders have distinctive clinical and immunopathological features and

different treatment. It is known that the MHC class II region produces the strongest

effect on MS genetic susceptibility. However, HLA association studies in NMO

patients are fewer and based on small cohorts. In addition, the polymorphism of the

TNF gene locus located on chromosome 6 (6p21.31) has been involved in the

pathogenesis of various autoimmune diseases. This study has the purpose to

evaluate DRB1*, DQ* alleles and TNF promotor gene polymorphism (SNP pTNF-a) in

a cohort of Cuban MS and NMO patients. Disease–HLA associations were controlled

by population stratification. One hundred MS patients, 20 NMO patients, and 200

unrelated healthy controls (matched by age, gender, and ethnicity) were included.

Ancestry informative markers were used. Disease associated HLA

susceptibility/protection alleles were ascertained by PCR. Statistical analyses were

conducted using STRUCTURE 2.1, ADMIXMAP 3.7, SPSS 16.0 packages. In patients

with both diseases the European contribution was predominant. HLA-DRB1*15,

DRB1*14, DQA1*01, DQB1*06 alleles were associated with MS. A protection effect

was associated for HLA DRB1*01, *07, *10, *1101-1104 alleles respect to MS, and

for HLA-DRB1*10:01, DRB1*11:01-11:04

alleles respect to NMO. Regarding disease association to SNP pTNF-a, a possible

protective role was demonstrated for NMO at SNP position –308G/A (OR = 0.3; p<

0.001), and for MS at SNP positions 238G/A, 308G/A, and 376G/A (OR= 0.4, 0.51,

0.3 respectively; p <0.01).

Assessment of variants in the huge Titin gene - NGS results in 2700

myopathy patients

Bjarne Udd, Professor in Neurology and Neuromuscular Disorders

Tampere Neuromuscular Center, Tampere University and University Hospital, and Folkhälsan Institute of Genetics, Biomedicum, Helsinki, Finland

bjarne.udd@netikka.fi Because of its sheer size, variants in the titin gene (TTN), which is expressed in

skeletal and cardiac muscle and associated to a range of inherited muscle disorders,

are detected frequently in both healthy and affected individuals. Unambiguous

interpretation of molecular findings is almost impossible in many patients with

myopathies or cardiomyopathies. Although the guidelines issued by the American

College of Medical Genetics and Genomics (ACMG) and the Association for

Molecular Pathology (AMP) are an excellent starting point, specific TTN features

may require refinement of the criteria for a correct interpretation.

We systematically re-evaluated the ACMG/AMP criteria for the classification of TTN

missense variants in the context of inherited skeletal muscle disorders. We

collected and re-analyzed TTN genetic findings from 2662 patients with a skeletal

muscle disorder and carried out a systematic analysis of rare TTN variants in publicly

available databases.

Using our dataset we identified clinically irrelevant and relevant variants. Evaluating

these gene variants using established guidelines, we identified pitfalls questioning

their uncritical use in the case of TTN.

Conclusion

Stringent criteria are needed to classify TTN missense variants as disease-related.

We suggest adjustments are made to the guidelines and strongly encourage a closer

cross-field collaboration among all the different specialists working on titin.

IMPLEMENTATION OF GENOMIC MEDICINE TO GUIDE DRUG

SELECTION AND MITIGATE RISKS

J. Kevin Hicks PharmD PhD

Personalized Medicine Specialist Department of Individualized Cancer Management

Moffitt Cancer Center

mailto:James.Hicks@moffitt.org For cancer management, both the germline and somatic genome are important for

guiding drug selection and mitigating risks. This talk highlights the use of germline

and somatic genomic data to guide therapy. An example of germline testing to

guide drug selection and dosage is a quality improvement pilot implemented at

Moffitt Cancer Center where CYP2C19 was utilized to guide voriconazole dosing. In

particular, CYP2C19 rapid metabolizers were recommended to receive a higher dose

of voriconazole to avoid sub-therapeutic plasma concentrations. CYP2C19-guided

voriconazole dosing was compared between pre-intervention (voriconazole 200 mg

twice daily) and post-intervention (voriconazole 300 mg twice daily). Only 46.2% of

CYP2C19 rapid metabolizers receiving voriconazole 200 mg twice daily achieved a

therapeutic concentration, whereas 70.2% of rapid metabolizers receiving

voriconazole 300 mg twice daily achieved the goal trough concentration.

Another example of using genomic information to guide drug selection is

targeted next generation sequencing of tumors (i.e., somatic sequencing). At

Moffitt Cancer Center, over 4,000 patients have had their tumors sequenced to

identify opportunities for targeted therapy. Of interest, novel gene alternations

have been identified. As an example, a lung cancer patient was discovered to have a

ZCCHC8-ROS1 fusion that had not previously been reported in lung cancer.

Crizotinib was used to target the ZCCHC8-ROS1 fusion, with a progression-free

survival of 7 months and total duration of treatment of 15 months. These examples

demonstrate the feasibility of using both germline variations and somatic mutations

to guide drug selection and dosage in cancer patients.

Global analysis of genes expression regulation by the antitumor

peptide CIGB-300 in acute myeloid leukemia cell lines

Vázquez-Blomquist D1, Perera Y3, Miranda J2, Palenzuela D1, Perea S3

1Pharmacogenomic Group/System Biology Department, 2Bioinformatic Department, 3Pharmaceutical Department. Center for Genetic Engineering and Biotechnology

(CIGB), Havana, Cuba

dania.vazquez@cigb.edu.cu CIGB-300 is a peptide-based drug in investigation for oncologic application. It

targets the phosphoaceptor site of CK2 substrates in vitro and in vivo. Biological

effects and mechanism of actions of this peptide has been studied in human cell

lines derived from different type of cancers, through a wide range of experiments

mostly in solid tumor models. CIGB300 has been well tolerated in clinical trials,

including an exploratory protocol in acute leukemia. One of the goals of our

investigation with CIGB-300 is to understand the mechanisms of its action in acute

myeloid leukemia (AML). We performed a global analysis of gene expression

regulation using Affymetrix Clariom S HT technology in two AML-derived cell lines.

HL-60 and OCI-AML3, representing M2 and M4 AML types (~45%), were treated

with 40 M of CIGB-300 for 0.5 and 3 hours. Proper time-matched untreated

controls were included. From gene lists obtained for every group of treatment

(Génome Québec, Canada) we used different bioinformatics approaches to

understand and contrast genes regulation by CIGB-300 in each cell line, and

between cell lines, in two different times. We will analyze the data and propose

some mechanisms and pathways that are used by this antitumoral peptide to exert

its biological effects over the two cell lines. The description of common and

divergent mechanisms to accomplish similar effects with a similar antiproliferative

IC50 will be very valuable for the understanding of the peptide action. Moreover,

this would allow the proposal of clinical relevant biomarkers and the improved

treatment of AML-patients.

Variety of proteoforms in cancer cells

Stanislav Naryzhny

Orekhovich Institute of Biomedical Chemistry of Russian Academy of Sciences, Pogodinskaya 10, Moscow, 119121, Russia

B.P. Konstantinov Petersburg Nuclear Physics Institute, National Research Center "Kurchatov Institute", Orlova roscha, Gatchina, Leningrad region, 188300, Russia

snaryzhny@mail.ru Human proteome is tremendously complex and composed from diverse and

heterogeneous variants of proteins (proteoforms). Recent developments in mass

spectrometry and systematic approaches (technology and methodology) promise to

bring new insights into this complexity. Among biochemical methods, two-

dimensional gel electrophoresis (2DE) is a most powerful protein separation

technique that allows not just separating proteoforms but determining their physic-

chemical parameters (pI and Mw). Using combination of 2DE and mass

spectrometry (ESI LC-MS/MS), we have analyzed several human cancer cell lines

(HepG2, glioblastoma) along with normal cells. This allowed to detecting in a single

proteome ~20000 proteoforms coded by ~ 4000 genes. We also performed an

analysis of the quantitative distribution of different proteoforms in human cells and

found that the dependence of the number of proteoforms on their abundance is

described by Zipf's law: y = ax-1. The 3D-graphs showing distribution of

proteoforms in 2DE map were also generated. We have performed comparative

analysis of these graphs (≥1000 pairs) between normal and cancer cells. High

variability and dynamics of many proteins was revealed. A special attention has

been paid to the proteins that are the potential biomarkers for glioblastoma and

hepatocarcinoma. This can be a key for identification of proteoforms directly

related to cancerogenesis, and such proteoforms could be the potential biomarkers

or targets for therapy.

Keywords: proteoform, dynamics, abundance, 2DE, proteome, ESI LC-MS/MS

This work was funded by a grant of RSF (Russian Science Foundation) # 14-25-

00132. Mass-spectrometry measurements were performed using the equipment of

“Human Proteome” Core Facilities of the Institute of Biomedical Chemistry (Russia)

which is supported by Ministry of Education and Science of the Russian Federation

(agreement 14.621.21.0017, unique project ID RFMEFI62117X0017).

Nutriepigenomics in Cancer Development

Melina Mitsiogianni 1, Ioannis Anestopoulos 2, Aglaia Pappa 2 and Mihalis Panagiotidis 1*

1 Northumbria University, Department of Applied Sciences, Newcastle Upon Tyne, UK

2 Democritus University of Thrace, Department of Molecular Biology & Genetics, Alexandroupolis, Greece

m.panagiotidis@northumbria.ac.uk With respect to the epigenetic machinery, modifications in DNA methylation

patterns, histone protein modifications and miRNA expression profiling lead to an

altered expression state of several genes involved in various cellular cascades

including cell cycle, cell proliferation, apoptosis, etc. On the other hand, a wide

range of phytochemicals have shown to exert a plurality of anti-cancer effects

including anti-apoptotic, anti-angiogenic, anti-inflammatory, etc. Given that

epigenetic alterations are potentially reversible modifications, there is a growing

interest (over the last few years) on the beneficiary effect of various small molecule

compounds (including phytochemicals) as treatment options for various

malignancies. Such is the case with isothiocyanates (the major biologically active

products found in cruciferous vegetables) capable of mediating an anti-cancer

response. To this end, their chemo-preventive action is mainly attributed to a wide

range of anti-cancer properties, including regulation of the epigenetic machinery.

Current evidence from our group and others strongly supports the role of

isothiocyanates as potent epigenetic modulators capable of interacting with the

epigenome in order to restore the normal epigenetic landscape. The ability of these

compounds together with other phytochemicals (e.g. resveratrol, genistein,

curcumin, EGCG, etc.) has raised the awareness on the concept of the epigenetic

therapy as a therapeutic alternative in cancer treatment.

POSTER SESSION Hicacos II Room BioInfOMICS-01 "Pilot study: Study of utility of depressive symptom screening

through measurement of saliva biomarker" Sang Yeol, Lee, MD, PhD. 1* , Eunsung Lim2, MD, PhD., Won-Myong Bahk3, MD, PhD, Youung Joon Kwon4, MD, PhD, InKi Sohn5,MD,PhD.

BioInfOMICS-02 Decreased Quality of life in Elderly Patients with Subsyndromal Depression Moon-Doo Kim MD, PhD, Young-Joon KwonMD,PhD, Bo-HyunYoonMD,PhD, Won-Myong Bahk

BioInfOMICS-03 Salivary cortisol level in sleep-disordered breathing patients Jong-Hyun Jeong, Inki Sohn, Jeong Seok Seo, Won-Myong Bahk, Kwanghun Lee

BioInfOMICS-04 Antidepressants and Mood Stabilizers: Novel Research Avenues and Clinical Insights for Bipolar Depression Won-Myong Bahk, Young Sup Woo, Kwanghun Lee, Bo-Hyun Yoon, Moon-Doo Kim, Duk-In Jon, Young Joon Kwon, In Hee Shim

BioInfOMICS-05 Associations between immune activation and the current severity of the "with anxious distress" specifier in patients with depressive disorders Won-Myong Bahk, Kwanghun Lee, Bo-Hyun Yoon, Kyung Joon Min, Duk-In Jon, Young Joon Kwon, Eunsung Lim

BioInfOMICS-06 There is a correlation between plasma erythropoietin levels and attention deficit hyperactivity disorder symptoms Se-hoon Shim, Young Joon Kwon, Jong-Hyun Jeong, Kyung Joon Min, Eunsung Lim

BioInfOMICS-07 Plasma glial-derived neurotrophic factor in attention deficit hyperactivity disorder Inki Sohn , Sang-Yeol Lee , Bo-Hyun Yoon , Duk-In Jon, Se-hoon Shim

BioInfOMICS-08 Korean Medication Algorithm for Bipolar Disorder: changes in preferred medications for mania over 16 years Duk-In Jon, MD, Hallym University Sacred Heart Hospital, Korea; Jeong-Seok Seo, MD, Konkuk University Chungju Hospital, Korea; Bo-Hyun Yoon, MD

BioInfOMICS-09 Association Study between Amisulpride Treatment Response and Dopamine D3 Receptor Gene Polymorphisms in schizophrenic patients Kwanghun Lee, Duk-In Jon, Sang-Yeol Lee, Jong-Hyun Jeong, Seo Jeongseok, Jung-gu Lee

BioInfOMICS-10 Effects of LY341495 on the dendritic outgrowth and spine formation in the rat hippocampal neuron under toxic condition Kwanghun Lee, Duk-In Jon, Sang-Yeol Lee, Jong-Hyun Jeong, Jeong Seok Seo, Mi Kyoung Seo , and Jung Goo Lee and Sung Woo Park

BioInfOMICS-11 Association between glycogen synthase kinase-3β gene polymorphisms and attention deficit hyperactivity disorder in Korean children: A preliminary study Jeong Seok Seo, Se-Hoon Shim, Jong-Hyun Jeong, Kyung Joon Min, Moon-Doo Kim

BioInfOMICS-12 A case-control association study of serotonin 1A receptor gene and tryptophan hydroxylase 2 gene in attention deficit hyperactivity disorder Eunsung Lim, Se-Hoon Shim, Sang-Yeol Lee, Kwanghun Lee, Won-Myong Bahk

BioInfOMICS-13 Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD) Young-Joon Kwon*, Se-hoon Shim, Sang-Yeol Lee, Moon-Doo Kim, Jong-Hyun Jeong

BioInfOMICS-14 Liraglutide activates mTORC1 signaling and AMPA receptors in rat hippocampal neurons under toxic conditions Bo-Hyun Yoon, Won-Myong Bahk, Kyung Joon Min, Eunsung Lim, Moon-Doo Kim, Mi Kyoung Seo , and Jung Goo Lee and Sung Woo Park

BioInfOMICS-15 Interaction of TNF-alpha (-308 GA) polymorphism and HLA-

DRB1/DQA1 alleles associated with susceptibility to multiple sclerosis Cintado A, Fernández-de-Cossío ME, Nazabal M, Ale A, Díaz T, Villarreal A, Camacho H, Grass D, Cervantes M, Pavon N, Benitez JV, Cabrera JA, Pentón-Rol G

BioInfOMICS-16 Comparative study of gene expression in the colon of rat biomodel with ulcerative colitis, treated or not with Pellet-EGF Camacho, H; Roca, J; Guillen, IA; Aguilera, A; Palenzuela, DO; Silva, JA; Estrada, R; Gell, O; Berlanga, J and Novoa, LI

BioInfOMICS-17 Expression profile of genes related to apoptosis in the colon of rats with ulcerative colitis treated with EGF Roca, J; Camacho, H; Guillen, IA; Aguilera, A; Palenzuela, DO; Silva, JA; Estrada, R; Gell, O; Delgado, Y; Berlanga, J and Novoa, LI

BioInfOMICS-18 Identification of the reference materials proteins from Saccharomyces cerevisiae by 2DE and Mass Spectrometry Sosa, P; Quiñones, M; Ramos, Y; Besada, V; Aldama, Y; Jiménez, Y; López, R; Rodríguez, C; Izquierdo, M; Costa, L; Alfonso, I; Pujol, V; González, LJ

BioInfOMICS-19 Characterization of low‐abundance species in the active pharmaceutical ingredient of a synthetic peptide CIGB‐300 Espinosa, LA; Garay, H; Perera Y; Sánchez A; Diago D; Perea S; Besada V; Reyes O; González LJ

BioInfOMICS-20 Targeting protein hydrophilic regions by MS via in-solution buffer-free trypsin digestion Espinosa, L. A.; Betancourt, L.; Ramos, Y.; Becquet, M.; Nelson, E.; Sánchez, A.; Marko-Vargas, G.; González, L. J.; Besada, V.

BioInfOMICS-21 In Silico Assessment of Potential Druggable Pockets on the Surface of Nucleophosmin Vieyto-Nuñez, JC; Guirola-Cruz, O; Perera-Negrin,

BioInfOMICS-22 In silico analysis of the interaction between the HLA II receptor associated with Reumetoid Arthritis and altered peptide ligand Fundora, B; Dominguez, MC; Guirola, O

BioInfOMICS-23 Impact of post-translational modifications on signaling pathways in patients with lung cancer Baez S; Palomares S; Guirola O

BioInfOMICS-24 Characterization of the chimeric glycoprotein E2-CD154 produced in the culture supernatant of HEK293 and cho cells Elianet Lorenzo

BioInfOMICS-25 Analysis of post-translational modifications in Acute Myeloid Leukemia and their impact in the discovery of new biomarkers Palomares, S; Guirola, O; Gonzalez, LJ

BioInfOMICS-26 Mass Spectrometric analysis and biological activity of Bm86-pP0: A peptide-conjugated vaccine candidate against ticks Alina Rodríguez-Mallón, Luis Javier González; Pedro E. Encinosa Guzmán, Yamil Bello Soto, Fabiola Almeida; Espinosa, L. A.; Julio Cesar Veyto, Gleysin Cabrera, Satomy Pouza, Samanta Jiménez; Alexei Licea-Navarro; Hilda Garay, Ania Cabrales, Mario Pablo Estrada

BioInfOMICS-27 Assessing the Impact and Cost Effectiveness of Free Comprehensive Health Care and Financial Support in Rural Mexico” Williamson AE, Ponce de Leon L, Macias V and Flores H. Department of Economics, Oxford University; Harvard Medical School, Boston; Partners in Health Mexico, Jaltenango.

POSTER SESSION ABSTRACTS

Pilot study: Study of utility of depressive symptom screening

through measurement of saliva biomarker

Sang Yeol, Lee, MD, PhD. 1* , Eunsung Lim2, MD, PhD., Won-Myong Bahk3, MD, PhD, Youung Joon Kwon4, MD, PhD, InKi Sohn5,MD,PhD.

1 Department of Psychiatry, School of Medicine, Wonkwang University

2 Department of Psychiatry, Shinsegae Hospital, Kimje, Republic of Korea 3Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The

Catholic University of Korea, Seoul, Republic of Korea 4 Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of

Medicine, Soonchunhyang University, Cheonan, Republic of Korea 5 Department of Psychiatry, Keyo Medical Foundation Keyo Hospital,,Uiwang,

Republic of Korea

psysangyeol@hanmail.net

The present study was conducted to assess the effectiveness of salivary biomarker analysis in screening for depressive symptoms. Method . In this study, salivary biomarkers (IL-10, IL-6, TNF-a, and serotonin) collected from 28 patients with depression and 28 normal controls were analyzed by enzyme-linked immunosorbent assay (ELISA). Additionally, demographic data of the participants were collected and their psychological characteristics were assessed using the following scales: Patient Health Questionnaire-9 (PHQ-9) and Center for Epidemiologic Studies Depression Scale (CES-D), to assess depressive symptoms; Generalized Anxiety Disorder-7 (GAD-7), to assess anxiety symptoms; and Perceived Stress Scale-10 (PSS-10) and Global Assessment of Recent Scale (GARS), to assess stress. Differences in the salivary biomarkers of patients with depression and those of the normal control group were analyzed, and correlations between salivary biomarker levels and psychological scale scores were computed.

Result Regarding salivary biomarkers, there were between-group differences in IL-6 (t = −2.562, p < 0.05) and IL-10 (t = 3.838, p < 0.001), but not in TNF-a or serotonin. Regarding the correlation between salivary biomarkers and psychological variables, IL-6 was significantly correlated with PHQ-9 (r = 0.241, p < 0.05) and CES-D (r = 0.212, p > 0.05), while IL-10 was significantly correlated with PSS-10 (r = 0.237, p < 0.05), PHQ-9 (r = 0.337, p < 0.01), GAD-7 (r = 0.291, p < 0.05), CES-D (r = 0.327, p < 0.01) and GARS (r = 0.224, p < 0.05). Neither serotonin nor TNF-a showed a significant correlation with any psychological variable. Conclusion These findings show that salivary biomarkers can be used to screen for depressive symptoms, suggesting their applicability in clinical practice and diverse social situations. Key words Depressive symptoms, Biomarker, Saliva, ELISA, Stress

Decreased Quality of life in Elderly Patients with Subsyndromal

Depression

Moon-Doo Kim MD, PhD*1, Young-Joon KwonMD,PhD2, Bo-HyunYoonMD,PhD3, Won-Myong Bahk4

1*Department of Psychiatry, Jeju National University Hospital, Jeju, Korea, 2Department of Psychiatry, Soonchunhyang University Chun-An Hospital,

3Naju National Hospital. 4Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The

Catholic University of Korea, Seoul, Republic of Korea

mdkim0721@gmail.com

Objectives Non-major depression with fewer symptoms than required for a DSM-IV diagnosis of major depressive disorder (MDD) has consistently been found to be associated with functional impairment. In this study, we aim to estimate the quality of life in elderly patients with subsyndromal depression (SSD) compared with non-depressive elderly (NDE). Mehthods The Korean version of Mini International Neuropsychiatric Interview was administered to 194 of outpatients with depression and 108 of normal control group. SSD is defined as having five or more current depressive symptoms with core depressive symptoms (depressive mood or loss of interest or pleasure) during more than half a day and more than seven days over two weeks. Depression was evaluated by the Korean form of Geriatric Depression Scale of a 15-item short version (KGDS-15). Global cognition was assessed by the Korean Version of Revised form of Hasegawa Dementia Scale (K-HDS) and Mini-Mental State Examination in the Korean version of CERAD assessment packet (MMSE-KC). Subjective cognitive impairment was assessed Subjective Memory Complain Questionnaire (SMCQ). Quality of life was evaluated by The Korean Version of Short-Form 36-Item Health Survey (SF-36).

Results The scores of physical component summary (PCS)(F=9.274, p=0.003, ANCOVA) and mental component summary (MCS) (F=53.166, p<0.001, ANCOVA) in the SSD group were lower than those in NDE group with adjustment for age, gender, and education(by SF-36) Conclusion Subjects with SSD, as well as those with MDD, were experienced low quality of life in both physical and mental aspects, compared to NDE group.

Salivary cortisol level in sleep-disordered breathing patients Jong-Hyun Jeong1*, Inki Sohn2, Jeong Seok Seo3, Won-Myong Bahk4, Kwanghun Lee5 1Department of Psychiatry, St. Vincent's Hospital, College of Medicine, The Catholic

University of Korea, Suwon, Korea 2Department of Psychiatry, Keyo Hospital, Keyo Medical Foundation, Uiwang, Korea 3Department of Psychiatry, School of Medicine, Konkuk University, Chungju, Korea 4Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The

Catholic University of Korea, Seoul, Korea 5Department of Psychiatry, College of Medicine, Dongguk University, Gyeongju,

Republic of Korea

anton3@catholic.ac.kr

Objective: Sleep-disordered breathing (SDB) is associated with stress system activation involving the hypothalamic–pituitary–adrenocortical (HPA) axis. The relationships among salivary cortisol, a measure of the HPA axis, and objective parameters of polysomnography (PSG) and subjective sleep symptoms were examined. Methods: Our prospective study enrolled 80 children who had a physical examination, underwent overnight PSG, and completed the Korean version of the modified pediatric Epworth sleepiness scale (KMPESS) and OSA-18 (KOSA-18) questionnaires. Saliva was collected at night before PSG and in the early morning after PSG. Results: Subjects (N = 92) were divided into control (n = 36, apnea–hypopnea index [AHI] < 1) and SDB(n = 56, AHI ≥ 1) groups; the SBD group was subdivided into mild (1 ≤ AHI < 5) and moderate to severe (AHI ≥ 5) groups. Although salivary cortisol before PSG (n-sCor) did not show a significant change with SDB severity, salivary cortisol after PSG (m-sCor) significantly decreased with SDB severity. This decrease resulted in a salivary cortisol ratio (r-sCor) that was significantly different between the control group and the two SDB subgroups. The m-sCor and sub-sCor of the total group as well as the m-sCor, sub-sCor, and r-sCor of the SDB group were negatively related to the oxygen desaturation index (ODI). The m-sCor and r-sCor in the SDB

group also were related to subjective sleep symptoms (quality of life [QOL] by KOSA-18). Conclusions: Among the four salivary cortisol parameters, r-sCor was negatively associated with SDB severity, ODI, and QOL (KOSA-18), which may indicate a chronically stressed HPA axis. These results demonstrate that salivary cortisol may be a useful biomarker of SDB. Keywords: Salivary cortisol, Polysomnography, Stress, Sleep-disordered breathing

Antidepressants and Mood Stabilizers: Novel Research Avenues

and Clinical Insights for Bipolar Depression. Won-Myong Bahk1*, Young Sup Woo1, Kwanghun Lee2, Bo-Hyun Yoon3, Moon-Doo

Kim4, Duk-In Jon5, Young Joon Kwon6, In Hee Shim7

1Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

2Department of Psychiatry, College of Medicine, Dongguk University, Gyeongju, Republic of Korea

3Department of Psychiatry, Naju National Hospital, Naju, Republic of Korea 4Department of Psychiatry, Jeju National University Hospital, Jeju, Republic of Korea

5Department of Psychiatry, Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Republic of Korea

6Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea

7Department of Psychiatry, Cancer Center, Dongnam Institute of Radiological & Medical Sciences, Busan, Republic of Korea

wmbahk@catholic.ac.kr

The concept of the bipolar-spectrum and of mixed features being a bridge between major depressive disorders and bipolar disorders (BDs) has become increasingly important in mood-disorder diagnoses. Under these circumstances, antidepressants (ADs) and mood stabilizers (MSs) should be used with caution in the treatment of major depressive episodes (MDEs) and to obtain long-term stability in BDs. Before treating MDEs, screening tools, specific symptom evaluation and medical history should be used to distinguish between bipolarity and mixed features in patients for whom AD monotherapy may present a risk. In these patients, a combination of ADs plus MSs or atypical antipsychotics is recommended, rather than AD monotherapy. Studies evaluating MSs for bipolar depression suggest that lamotrigine is the most reliable treatment and lithium has modest effects; there is a lack of clear evidence regarding the efficacy of valproate and carbamazepine. Recently, significant progress has been made with respect to the pathophysiology of mood disorders

and the application of potential biomarkers. There is an opportunity to study novel drug mechanisms through the rediscovery of fast-acting drugs such as ketamine. It is anticipated that future research developments will involve the discovery of potential targets for new drugs and their application to personalized treatments.

Associations between immune activation and the current severity

of the "with anxious distress" specifier in patients with depressive

disorders Won-Myong Bahk1*, Kwanghun Lee2, Bo-Hyun Yoon3, Kyung Joon Min4, Duk-In Jon5,

Young Joon Kwon6, Eunsung Lim7

1Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

2Department of Psychiatry, College of Medicine, Dongguk University, Gyeongju, Republic of Korea

3Department of Psychiatry, Naju National Hospital, Naju, Republic of Korea 4Department of Psychiatry, College of Medicine, Chung-Ang University, Seoul,

Republic of Korea 5Department of Psychiatry, Sacred Heart Hospital, College of Medicine, Hallym

University, Anyang, Republic of Korea 6Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of

Medicine, Soonchunhyang University, Cheonan, Republic of Korea 7Department of Psychiatry, Shinsegae Hospital, Kimje, Republic of Korea

Objective : Immune dysregulation may be linked with depressive disorders and in particular anxiety symptoms. This study compared the levels of immune factors, demographic and clinical characteristics of patients with depressive disorders between mild to moderate and moderate–severe to severe anxious distress groups. Methods : This study included 177 patients diagnosed with a depressive disorder who were hospitalized between March 2012 and April 2015. The patients were categorized into mild to moderate and moderate–severe to severe anxious distress groups, based on the Hamilton Depression Rating Scale (HAM-D) scores on the Agitation and Anxiety–Psychic subscales. The charts of the patients were reviewed to evaluate immune factors, including C-reactive protein (CRP) and white blood cell levels, confounding factors, such as smoking, other general medical disorders and

body mass index, and demographic and clinical characteristics, such as age, sex, total HAM-D scores, comorbidities, family history of mood disorders, suicidality, psychotic features and prescription patterns. Results : The moderate–severe to severe group tended to have higher CRP and monocyte levels compared with the mild to moderate group. After adjusting for the HAM-D scores, patients with moderate–severe to severe anxious distress had a significantly greater trend toward significance for suicidality and a higher rate of antipsychotic use. Conclusion : High levels of anxiety symptoms may modulate the inflammatory response and course of illness, affecting treatment planning.

There is a correlation between plasma erythropoietin levels

and attention deficit hyperactivity disorder symptoms

Se-hoon Shim1*, Young Joon Kwon1, Jong-Hyun Jeong2, Kyung Joon Min3, Eunsung Lim4

1 Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of

Medicine, Soonchunhyang University, Cheonan, Republic of Korea 2 Department of Psychiatry, St. Vincent's Hospital, College of Medicine, The Catholic

University of Korea, Suwon, Korea 3 Department of Psychiatry, Chung-Ang University Hospital, College of Medicine,

Chung-Ang University, Seoul, Republic of Korea 4 Department of Psychiatry, Shinsegae Hospital, Kimje, Korea

shshim2k@daum.net

Erythropoietin(EPO) is a circulating hormone that governs the rate of red blood cell production. There are a few animal models associating dopamine dysfunction with behavioral impairments that model ADHD. Epo has trophic effects on dopaminergic neurons. The aim of the present study was to examine the EPO plasma levels and determine whether there was any correlation between plasma EPO levels and clinical characteristics of ADHD. Plasma EPO levels were measured in 78 drug-naïve children with ADHD and 81 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in children and healthy controls. The ADHD group consisted of 64 boys and 14 girls, and the healthy control group consisted of 31 boys and 50 girls. The median plasma EPO levels in ADHD children was 12.9 mIU/mL, whereas it was 12.0 mIU/mL in the healthy controls. This difference was not statistically significant. Participants in the highest tertiles of plasma EPO had a 1.49 times higher risk of ADHD than those in the lowest tertile, and those in the second highest tertile had a 2.39 times higher risk of ADHD than those in the lowest tertile. A logistic regression showed that the plasma EPO levels were not associated with ADHD after adjusting for age and gender. Plasma EPO levels significantly correlated positively with K-ARS scores including hyperactivity – impulsivity and total scores as determined by Spearman’s

correlation test in ADHD children and healthy controls. A linear regression analysis performed adjusting for age and gender also indicated that the significant difference in inattention score comparing participants in the highest with those in the lowest tertile of plasma EPO was 1.70. The significant difference in hyperactivity-impulsivity score comparing participants in the second highest with those in the lowest tertile of plasma EPO was 2.00. The mean total K-ARS scores comparing participants in the highest tertile of plasma EPO levels were 4.2, significantly higher than those in the lowest tertile group. These findings suggest plasma EPO levels in untreated ADHD children did not differ with healthy controls. However, plasma EPO levels had a significant positive correlation with hyperactivity – impulsivity and K-ARS total scores in ADHD children and healthy controls. Further studies are required to determine the source and role of circulating EPO in ADHD.

Plasma glial-derived neurotrophic factor in attention deficit

hyperactivity disorder

Inki Sohn 1*, Sang-Yeol Lee 2, Bo-Hyun Yoon3 , Duk-In Jon4, Se-hoon Shim5

1 Department of Psychiatry, Keyo Hospital, Uiwang city , Republic of Korea 2 Department of psychiatry, Wonkwang university schook of medicine, Iksan,

Republic of Korea 3 Department of Psychiatry, Naju National Hospital, Naju, Republic of Korea

4 Department of Psychiatry, Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Republic of Korea

5 Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea

fiveway@daum.net

Recent evidence suggests that neurotrophic growth factor systems, including brain-derived neurotrophic factor, might be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Glial cell line-derived neurotrophic factor (GDNF) is from the transforming growth factor-β family and is abundantly expressed in the central nervous system, where it plays a role in the development and function of hippocampal cells. To date, no association studies have been done between ADHD and GDNF. Thus, here we investigate the hypothesis that there are differences in plasma GDNF levels between children with ADHD and healthy controls. Methods: Plasma GDNF levels were measured in 86 drug-naïve children with ADHD and 128 healthy children. The severity of ADHD symptoms was determined by scores on the Korean ADHD Rating Scale (K-ARS) in patients and healthy controls. Results: The median plasma GDNF levels in ADHD patients was 74.0 (IQR: 23.4–280.1) pg/ml versus 24.6 (IQR: 14.5–87.3) pg/ml in healthy controls; thus the median plasma GDNF levels in ADHD patients were significantly higher than in healthy controls (Mann–Whitney U-test, P < 0.01). Plasma GDNF levels were correlated positively with K-ARS subscale scores (inattention, hyperactivity–impulsivity and total), determined by Spearman's correlation test in ADHD patients

and healthy controls (r = 0.371, P < 0.01; r = 0.331, P < 0.01; and r= 0.379, P < 0.01, respectively). Conclusions: These findings suggest increased plasma GDNF levels in untreated ADHD patients. In addition, plasma GDNF levels had a significant positive correlation with inattention, hyperactivity–impulsivity and K-ARS total scores in ADHD patients and healthy controls. Further studies are required to determine the source and role of circulating GDNF in ADHD.

Korean Medication Algorithm for Bipolar Disorder: changes in

preferred medications for mania over 16 years

Duk-In Jon, MD, Hallym University Sacred Heart Hospital, Korea; Jeong-Seok Seo, MD, Konkuk University Chungju Hospital, Korea; Bo-Hyun Yoon, MD

Naju National Hospital, Korea; Kyung Joon Min, MD, Chung-Ang University Hospital, Korea; Won-Myong Bahk, MD, Yeouido St. Mary Hospital, The Catholic University of

Seoul , Korea

jazzphilic@gmail.com

Introduction: Many treatment guidelines for bipolar disorders have been introduced to assist clinical decision. Majority of these guidelines are based on evidences from clinical trials. The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed to adopt and maintain an expert-consensus paradigm which was more practical and specific to the atmosphere in Korea. In this research, preferred medication strategies for acute mania over four consecutively published KMAP-BP guidelines (2002, 2006, 2010, 2014, and 2018) were investigated. Methods: The KMAP-BP questionnaire using a nine-point scale had covered some specific clinical situations divided into subsections with many treatment options. A written survey asked about the appropriateness of various treatment strategies and treatment agents commonly used by clinicians as the first-line. Results: The most preferred initial treatment strategy for all subtypes of mania was a combination of mood stabilizer (MS) and atypical antipsychotic (AAP) in every edition. In contrast to MS monotherapy, the preference of combination therapy has been increased over time. Among MSs, lithium and valproic acid are almost equally preferred except in the mixed subtype where valproic acid is the most recommended MS. Carbamazepine was the first-line MS only in the first edition. Olanzapine, quetiapine, and aripiprazole were the preferred AAP for acute manic episode in later editions. This change might depend on the recent research results and safety profile. In cases of unsatisfactory response to the first-line medications, we recommended switching or adding another first-line agent. In KMAP-BP 2018, MS (more preferred as treatment of choice) or AAP monotherapy was first-line medication.

Discussion: The Korean experts have been increasingly convinced of the effectiveness of a combination therapy for acute manic episode. There have been evident preference changes: increased for AAP and decreased for carbamazepine.

Association Study between Amisulpride Treatment Response

and Dopamine D3 Receptor Gene Polymorphisms in

schizophrenic patients Kwanghun Lee*, Duk-In Jon, Sang-Yeol Lee, Jong-Hyun Jeong, Seo Jeongseok, Jung-

gu Lee

Department of Psychiatry, College of Medicine, Dongguk University, Gyeongju, Republic of Korea

Department of Psychiatry, Sacred Heart Hospital, College of Medicine, Hallym University, Anyang, Republic of Korea

Department of Psychiatry, Wonkwang University Hospital, College of Medicine, Iksan, Republic of Korea

Department of Psychiatry, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea

Department of Psychiatry, Konkuk university Hospital, College of Medicine, Chungju, Republic of Korea

Department of Psychiatry, Haeundae Paik Hospital, College of Medicine, Inje University, Busan, Republic of Korea

nostre6@msn.com

Objectives The aim of this study is to evaluate the association between rs6280 and rs905568 genetic polymorphism of DRD3 gene and the treatment response of amisulpride. Methods After six weeks treatment of amisulpride, 125 schizophrenia patients were interviewed based on the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression-Severity (CGI-S). The genotyping for rs6280 and rs905568 was performed using TaqMan single nucleotide polymorphism (SNP) genotyping assay. Results There was no significant difference in the frequency of genotype and allele of rs6280 between the responders and non-re¬sponders based on the total, positive, and general score of PANSS and CGI-S score. However, there was a significant association between this SNP and treatment response in the negative

score of PANSS (χ2 = 5.23, p = 0.022). There was no significant association between rs905568 and the response in positive, negative, general, and total PANSS score and CGI-S score. Conclusions This is the first positive association study between DRD3 gene and the treatment response of negative symptoms to amis¬ulpride in Korean schizophrenia patients. A larger scale research on more SNP of the DRD3 gene will make a progress in the study of pharmacogenetics on the treatment response of the amisulpride.

Key Words Treatment response ㆍAmisulpride ㆍDRD3 gene ㆍPolymorphisms

rs6280.

Effects of LY341495 on the dendritic outgrowth and spine

formation in the rat hippocampal neuron under toxic

condition KwangHun Lee1, Duk-In Jon2, Sang-Yeol Lee3, Jong-Hyun Jeong4, Jeong Seok Seo5, Mi

Kyoung Seo 6, and Jung Goo Lee 6,7,8 and Sung Woo Park 6,7,9*

1Department of Psychiatry, College of Medicine, Dongguk University, Gyeongju, Korea.

2Department of Psychiatry, Sacred Heart Hospital, Hallym University, Anyang, Korea. 3Department of Psychiatry, College of Medicine, Wonkwang University, Iksan,

Korea. 4Department of Psychiatry, College of Medicine, The Catholic University of Korea,

Seoul, Korea. 5Department of Psychiatry, School of Medicine, Konkuk University, Chungju, Korea.

6Paik Institute for Clinical Research, Inje University, Busan, Korea. 7Department of Health Science and Technology, Graduate School, Inje University,

Korea 8Department of Psychiatry, Inje University Haeundae Paik Hospital, Busan, Korea.

9Department of Convergence Biomedical Science, College of Medicine, Inje University, Busan, Korea.

swpark@inje.ac.kr

Purpose: Ketamine is correlated with increased synaptogenesis via activation of AMPA receptors and mTOR signaling. Studies in ketamine support its rapid-acting antidepressant properties. A mGlu2/3 antagonist, LY341495, has been proposed to exert an antidepressant effect via mechanisms similar to ketamine. The purpose of this study was to investigate the effects of LY341495 and ketamine on neuroplasticity dexamethasone-induced neurotoxicity in hippocampal cultures, and related intracellular mechanisms.

Methods: Ketamine (50-100 μM) and LY341495 (1-100 μM) were administered independently in primary hippocampal cells under both a control and a dexamethasone - induced toxic condition (500 μM for 5 days). Changes to dendritic length and spine density were evaluated. Results: Exposure to dexamethasone led to significant reductions in hippocampal spine density and total dendritic length. Treatment with ketamine and LY341495 significantly attenuated these aforementioned reductions after dexamethasone exposure. These positive effects were potentiated in dexamethasone condition rather than in the control condition. Pretreatment of primary hippocampal cells in the dexamethasone condition with NBQX (an AMPA receptor antagonist) and rapamycin (a selective mTOR inhibitor) significantly blocked positive effects of LY341495 and ketamine on total dendritic length and spine density. Conclusions: Our results indicate positive effects of LY341495 and ketamine on neuroplasticity which may be dependent on the activation of AMPA receptors and mTOR signaling. These results provide evidence to support antidepressant properties of LY341495 via a mechanism similar to that seen in ketamine. Key words: mGlu2/3 antagonist, ketamine, AMPA receptors, mTOR signaling, neuroplasticity, hippocampus

Association between glycogen synthase kinase-3β gene

polymorphisms and attention deficit hyperactivity disorder in

Korean children: A preliminary study Jeong Seok Seo1, Se-Hoon Shim2*, Jong-Hyun Jeong3, Kyung Joon Min4*, Moon-Doo

1Department of Psychiatry, School of Medicine, Konkuk University, Chung-ju, Republic of Korea

2Department of Psychiatry, Jeju National University Hospital, Jeju, Republic of Korea 3Department of Psychiatry, College of Medicine, The Catholic University of Korea,

Seoul, Korea 4Department of Psychiatry, Jeju National University Hospital, Jeju, Republic of Korea 5Department of Psychiatry, College of Medicine, Chung-Ang University, Seou,Korea

kjoonmin@gmail.com

Glycogen synthase kinase (GSK)-3β plays a key role in the phosphorylation and regulation of metabolic enzymes and many transcription factors. Recent studies have suggested the involvement of GSK-3β in the pathogenesis and treatment target of DA-associated neuropsychiatric disorders, which has led to consider GSK-beta as one of the candidate genes for those disorders. GSK-3β genes are likely to be involved in mechanisms underlying attention deficit hyperactivity disorder (ADHD). We investigated the association between −1727A/T and −50T/C SNPs of GSK-3β gene with ADHD. All ADHD subjects completed a comprehensive and standardized diagnostic test and psychological evaluation battery, including the parents' Korean version of the ADHD Rating Scale-IV (ARS). The genotype and allele frequencies of 103 ADHD patients and 173 normal controls were analyzed for −1727A/T and −50T/C SNPs of GSK-3β gene. There were statistically significant differences in the genotype distributions of the −1727A/T SNP of GSK-3β gene between the ADHD group and the control group. The frequency of the genotype AT was significantly higher in the ADHD patients.

Concerning the haplotype, there was a significant difference in the A–C haplotype frequency between the two samples. However, no differences in either the genotype distribution or in allele frequencies of−50C/T were observed between the two samples. In the parents version of K-ARS of all subjects, ANCOVA revealed that two subscales and the total score were significantly higher in the subjects with AT+TT genotypes than those with AA genotype after adjusting for age and gender. The odds ratio for the ADHD patients was 1.79, comparing the AT genotype group with the AA genotype group. Therefore, genotype AT is associated with a higher risk of ADHD. Our results suggest that the −1727A/T SNP of GSK-3β gene may affect susceptibility in ADHD. Further investigation with a larger number of subjects is needed to validate this finding.

A case-control association study of serotonin 1A receptor

gene and tryptophan hydroxylase 2 gene in attention deficit

hyperactivity disorder.

Eunsung Lim1, Se-Hoon Shim2, Sang-Yeol Lee3, Kwanghun Lee4, Won-Myong Bahk5

1Department of Psychiatry, Shinsegae Hospital, Kimje, Korea, 2Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of

Medicine, Soonchunhyang University, Cheonan, Republic of Korea 3Department of psychiatry, Wonkwang university school of medicine, Iksan,

Republic of Korea 4Department of Psychiatry, College of Medicine, Dongguk University, Gyeongju,

Republic of Korea 5Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine, The

Catholic University of Korea, Seoul, Republic of Korea

calvaria0416@hanmail.net

Serotonergic system-related genes are likely to be involved in mechanisms underlying attention deficit hyperactivity disorder (ADHD). We investigated the association of serotonin the 1A receptor C-1019G single nucleotide polymorphism (HTR1A C-1019G SNP) and tryptophan hydroxylase 2 gene –703G/T (TPH2 –703G/T) SNP with ADHD. All of the ADHD subjects completed a comprehensive and standardized diagnostic and psychological evaluation battery including the parents' Korean version of the ADHD Rating Scale-IV (ARS). The genotype and allele frequencies of 78 ADHD patients and 107 normal controls were analyzed for 5-HTR1A C-1019G and TPH2 –703G/T. There were statistically significant differences in the genotype distributions and allele frequencies of HTR1A C-1019G between the ADHD group and the control group. The homozygous allele C frequency was significantly higher in ADHD patients than in controls. However, no differences in either genotype distribution or in allele frequencies of TPH2 –703G/T were observed between the ADHD patients and the controls. In the ADHD patients, ANCOVA revealed that there were no significant

differences in the subscales and total score between the ADHD probands with the CC genotype and those with the CG and GG genotypes in ARS and the Continuous Performance Test (CPT) when adjusting for age and gender. The odds ratio comparing the CC genotype group with the CG genotype group and the C allele with G was 2.12 and 1.79 respectively. Therefore, genotype CC was associated with higher risk of ADHD. Our results suggest that the HTR1A C-1019G SNP may affect susceptibility to ADHD. Further investigation with a larger number of subjects is needed in order to confirm this finding.

Increased levels of plasma brain-derived neurotrophic factor

(BDNF) in children with attention deficit-hyperactivity

disorder (ADHD)

Young-Joon Kwon1*, Se-hoon Shim1, Sang-Yeol Lee2, Moon-Doo Kim3, Jong-Hyun Jeong4

1 Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of

Medicine, Soonchunhyang University, Cheonan, Republic of Korea 2 Department of psychiatry, Wonkwang university schook of medicine, Iksan,

Republic of Korea 4 Department of Psychiatry, Shinsegae Hospital, Kimje, Korea 3 Department of Psychiatry, Jeju National University Hospital, Jeju, Republic of

Korea 4 Department of Psychiatry, St. Vincent's Hospital, College of Medicine, The Catholic

University of Korea, Suwon, Korea

alienist1@naver.com

Recent reports have suggested a pathophysiological role of brain-derived neurotrophic factor (BDNF) in attention deficit-hyperactivity disorder (ADHD). We evaluated the plasma levels of BDNF in patients with ADHD. Plasma BDNF levels were measured in 41 drug naive ADHD patients and 107 normal controls. The severity of ADHD symptoms was determined by patient scores on the ADHD rating scale (ARS) and the computerized ADHD diagnostic system (ADS). ANCOVA with age and gender as covariates showed that the mean plasma BDNF levels were significantly higher in ADHD patients than in normal controls. There were also significant differences in plasma BDNF levels of ADHD patients and those of normal controls for males and females. We also found a significant correlation between plasma BDNF levels and omission errors in ADS outcome-variable T-scores. Our study suggests that there is an increase of plasma BDNF levels in untreated ADHD patients, and that plasma BDNF levels had a significant positive correlation with the severity of inattention symptoms. Further studies are required to elucidate the source and role of circulating BDNF in ADHD.

Liraglutide activates mTORC1 signaling and AMPA receptors

in rat hippocampal neurons under toxic conditions

Bo-Hyun Yoon1, Won-Myong Bahk2, Kyung Joon Min3, Eunsung Lim4 , Moon-Doo Kim5, Mi Kyoung Seo 6, and Jung Goo Lee 6,7,8 and Sung Woo Park 6,7,9*

1Department of Psychiatry, Naju National Hospital, Naju, Korea.

2Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul, Korea.

3Department of Psychiatry, College of Medicine, Chung-Ang University, Seoul, Korea.

4Department of Psychiatry, Shinsegae Hospital, Kimje, Korea. 5Department of Psychiatry, Jeju National University Hospital, Jeju, Korea.

6Paik Institute for Clinical Research, Inje University, Busan, Korea. 7Department of Health Science and Technology, Graduate School, Inje University,

Korea 8Department of Psychiatry, Inje University Haeundae Paik Hospital, Busan, Korea.

9Department of Convergence Biomedical Science, College of Medicine, Inje University, Busan, Korea.

swpark@inje.ac.kr

Purpose: The aim of the present study was to determine whether treatment with liraglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, would alter mammalian target of rapamycin complex 1 (mTORC1) signaling and/or α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor activity under dexamethasone-induced toxic conditions. Methods: Western blot analyses were performed to assess changes in mTORC1-mediated proteins, brain-derived neurotrophic factor (BDNF), and various synaptic proteins (PSD-95, synapsin I, and GluA1) in rat hippocampal cultures under toxic conditions induced by dexamethasone, which causes hippocampal cell death. Hippocampal dendritic outgrowth and spine formation were measured using immunostaining procedures.

Results: Dexamethasone significantly decreased the phosphorylation levels of mTORC1 as well as its downstream proteins. However, treatment with liraglutide prevented these reductions and significantly increased BDNF expression. The increase in BDNF expression was completely blocked by rapamycin and 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX). Liraglutide also recovered dexamethasone-induced decreases in the total length of hippocampal dendrites and reductions in spine density in a concentration-dependent manner. However, the positive effects of liraglutide on neural plasticity were abolished by the blockade of mTORC1 signaling and AMPA receptors. Furthermore, liraglutide significantly increased the expression levels of PSD-95, synapsin I, and GluA1, whereas rapamycin and NBQX blocked these effects. Conclusions: The present study demonstrated that liraglutide activated mTORC1 signaling and AMPA receptor activity as well as increased dendritic outgrowth, spine density, and synaptic proteins under toxic conditions in rat primary hippocampal neurons. These findings suggest that GLP-1 receptor (GLP-1R) activation by liraglutide may affect neuroplasticity through mTORC1 and AMPA receptors. Key words: mTORC1, AMPA receptor, GLP-1 receptor, liraglutide, neuroplasticity, toxic condition

Interaction of TNF-alpha (-308 GA) polymorphism and HLA-

DRB1/DQA1 alleles associated with susceptibility to multiple

sclerosis.

Cintado A, Fernández-de-Cossío ME1, Nazabal M1, Ale A1, Díaz T1, Villarreal A1, Camacho H 1, Grass D2, Cervantes M1, Pavon N2, Benitez JV1, Cabrera JA2, Pentón-

Rol G1.

1Pharmacogenomics Department. Biomedical Research Division. Center for Genetic Engineering and Biotechnology, 31 entre 158 & 190, Cubanacán, Playa, Cuba.

2International Center of Neurological Restoration. Ave 25 no 15805 entre 158 & 160 Cubanacan Playa.

alberto.cintado@cigb.edu.cu

Multiple sclerosis (MS) is considered a chronic autoimmune disease, characterized by demyelination and inflammation of the central nervous system. It is a typical complex disease determined both by genetic and environmental risk factors. Polymorphisms in TNF-alpha (pTNF-a) promoter region and HLA DQ/DR alleles were implicated in MS risk in several association studies. In the present study, we analyzed haplotype associations between pTNF-a and HLA DQA/DRB alleles and susceptibility to MS on Cuban patients. 100 patients and 200 unrelated controls participated in the study. pTNF-a genotypes were determined by Taqman assay method. HLA DQ/DR alleles were genotyping by PCR amplification, using sequence-specific primers (PCR-SSP). Allele and haplotype frequencies were estimated by means of expectation maximization algorithm. Statistic associations were calculated using the Chi-square test. Odd ratios (OR) with 95% confidence intervals (95%) were calculated using Fisher's method. HLA-DRB1*1501 allele was more frequent among patients (OR=2.84, P=0.001). TNF-α -308 A allele and A/A genotype had higher frequency among MS patients than control subjects (G vs A: OR=2.0, P<0.05). Moreover, we observed that pTNFa -308 in combination with pTNFa -237, HLA DRB1*1501 and HLA DQA1* 0102 increased susceptibility to MS (p<0.05 OR=4.1). Our results have shown that the combination between HLA-DRB1/DQA1 allele with

TNF-α -308 G/A, -237 G/A polymorphism are associated with the susceptibility of multiple sclerosis in Cuban population.

Comparative study of gene expression in the colon of rat biomodel

with ulcerative colitis, treated or not with Pellet-EGF.

Camacho, H13; Roca, J13; Guillen, IA13; Aguilera, A2; Palenzuela, DO1; Silva, JA1; Estrada, R1; Gell, O1; Berlanga, J1 and Novoa, LI1

1Biomedical Research Division. Center for Genetic Engineering and Biotechnology.

La Habana. Cuba 2Development Division. Center for Genetic Engineering and Biotechnology. La

Habana. Cuba 3These authors equally contributed to these results.

hamlet.camacho@cigb.edu.cu

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease, causing inflammation and ulcers in intestinal epithelium. The diagnosis of the disease and the possible prediction of the development of colon cancer from prolonged illness are still unclear. We use an animal model of colitis based on the use of dextran sodium sulfate (DSS) to evaluate the effect of the application of EGF-Pellet in the expression of genes involved in inflammation, oxidative stress and restoration of the intestinal epithelium. Materials and methods: The gene expression analysis was conducted with distal colon biopsies of male Wistar rats. Total RNA extraction was performed using the QIAcube platform. Quality control of RNA was performed with the Nanodrop and Bioanalyzer. The RNA was employed in quantitative real time polymerase chain reaction (qPCR) to measure the differential expression of 44 genes. Results: When comparing the results of expression obtained in the study with the model treated with EGF with untreated animals, an opposite regulation of genes involved in the processes of inflammation, oxidative stress, formation of the epithelial barrier and map kinases and the b catenin pathways was observed. A positive effect of treatment with Pellet-EGF was observed by decreased expression of pro-inflammatory cytokines and oxidative stress related genes. Furthermore, an increase of expression of genes involved in proliferation and restoring of the intestinal epithelium was observed. Conclusions: In general, treatment with EGF

pellets induced differential gene expression that may promote inhibition of inflammation, oxidative stress and damage to epithelial tissue.

Expression profile of genes related to apoptosis in the colon of rats

with ulcerative colitis treated with EGF

Roca, J13; Camacho, H13; Guillen, IA1; Aguilera, A2; Palenzuela, DO1; Silva, JA1; Estrada, R1; Gell, O1; Delgado, Y1; Berlanga, J1 and Novoa, LI1

1Biomedical Research Division. Center for Genetic Engineering and Biotechnology.

La Habana. Cuba 2Development Division. Center for Genetic Engineering and Biotechnology. La

Habana. Cuba 3These authors equally contributed to these results.

juan.roca@cigb.edu.cu

Introduction: The integrity of the intestinal epithelium results from a balance between the formation of new cells and the death of senescent cells. The deregulation of cell death pathways in intestinal epithelial cells may be involved in the pathogenesis of inflammatory bowel disease. A large number of apoptotic bodies have been observed in biopsies taken from patients suffering from Ulcerative Colitis (UC). A large number of apoptotic bodies have been observed in biopsies taken from patients suffering from UC. We use an animal model of colitis based on the use of dextran sodium sulfate (DSS) to evaluate the effect of the application of EGF-Pellet in the expression of 22 genes involved in apoptosis. Materials and methods: The gene expression analysis was conducted with distal colon biopsies of male Wistar rats. Total RNA extraction was performed using the QIAcube platform. Quality control of RNA was performed with the Nanodrop and Bioanalyzer. The RNA was employed in quantitative real time polymerase chain reaction (qPCR) to measure the differential expression. Results: More than 50% of the genes analyzed showed statistically significant changes in their expression. Of these, two anti-apoptotic genes increased their expression, while the genes that decreased their expression were pro-apoptotic genes and genes related to the TNFα signal transmission pathway. Conclusions: In the animal model of UC, treatment with EGF-pellets induced a differential gene expression that may lead to a decrease in apoptosis, which would favor the integrity of the intestinal epithelium.

Identification of the reference materials proteins from

Saccharomyces cerevisiae by 2DE and Mass Spectrometry

Sosa, P1; Quiñones, M1; Ramos, Y1; Besada, V1; Aldama, Y2; Jiménez, Y2; López, R2; Rodríguez, C2; Izquierdo, M2; Costa, L2; Alfonso, I3; Pujol, V3; González, LJ1

1 Proteomics Group, Systems Biology Department, Center for Genetic Engineering

and Biotechnology, Havana, Cuba. 2Quality Control Department, Center for Genetic Engineering and Biotechnology,

Havana, Cuba. 3 Production Department, Center for Genetic Engineering and Biotechnology,

Havana, Cuba.

mauricio.quinones@cigb.edu.cu patricia.sosa@cigb.edu.cu

In the biotechnology industry, regulatory agencies demand the characterization of contaminant proteins in biopharmaceutical products. Consequently, the generation of reference materials (RM) that contain the potential contaminant proteins is a key issue. These materials are obtained by performing negative fermentations of the host strain in the absence of the recombinant protein gen. Saccharomyces cerevisiae is one of the expression systems frequently used to obtain recombinant products. Here, we characterize the secretome of this microorganism using 2D gel electrophoresis (2DE) and mass spectrometry. The RM is composed of 6 main proteins, which represent more than 90% of the total protein content. We found that 94% of the detected proteins focus in pI range from 4 to 7. We identified 52 protein by LC-MS/MS of which 35 % are expressed in the cytoplasm. Using PEAKS and MASCOT search engines, we identified 35 proteins in common. Thioredoxin-1, Thioredoxin-2, Ubiquitin-60S ribosomal protein L40 and Heat shock protein SSA1 were detected by 2DE and mass spectrometry. Keywords: 2DE, reference standard, mass spectrometry

Characterization of low‐abundance species in the active

pharmaceutical ingredient of a synthetic peptide CIGB‐300 Espinosa, LA1; Garay, H2; Perera Y3; Sánchez A1; Diago D2; Perea S3; Besada V1; Reyes

O2; González LJ1

1Mass Spectrometry Laboratory, Department of Proteomics 2Peptide Synthesis Laboratory, Physics and Chemistry Department

3Molecular Oncology Laboratory, Pharmaceutical Department. Biomedical Research Center for Genetic Engineering and Biotechnology

luis.espinosa@cigb.edu.cu

CIGB‐300 is a first‐in‐class synthetic peptide‐based drug of 25 amino acids currently undergoing clinical trials in cancer patients. It contains an amidated disulfide cyclic undecapeptide fused to the TAT cell‐penetrating peptide through a ‐Ala spacer. Despite the clinical development, the characterization of impurities present in the active pharmaceutical ingredient has not been reported earlier. In the decision tree of ICHQ3A(R2) guidelines, the daily doses intake, abundance and identity of the impurities are pivotal nodes that define actions to be taken (reporting, identification, and qualification). For this, purity was first assessed by RP-HPLC (>97%) and low‐abundance impurities (≤0.27%) were collected and identified by mass spectrometry. Most of the impurities were generated during peptide synthesis, the spontaneous air oxidation of the reduced peptide and the lyophilization step. The most abundant impurity, with no biological activity, was the full‐length peptide containing Met17 transformed into a sulfoxide residue. Interestingly, parallel and antiparallel dimers of CIGB‐300 linked by two intermolecular disulfide bonds exhibited a higher anti-proliferative activity than the CIGB‐300 monomer. Likewise, very low abundance trimers and tetramers of CIGB‐300 linked by disulfide bonds (≤0.01%) were also detected. Here we describe for the first time the presence of active dimeric species whose feasibility as novel CIGB‐300 derived entities merits further investigation.

Targeting protein hydrophilic regions by MS via in-solution buffer-

free trypsin digestion Espinosa, L. A.1; Betancourt, L.2; Ramos, Y.1; Becquet, M.3; Nelson, E.4; Sánchez, A.2;

Marko-Vargas, G.2; González, L. J.1; Besada, V.1

1Mass 1Mass Spectrometry Laboratory, Department of Proteomics, Biomedical Research, Center for Genetic Engineering and Biotechnology

2Div. Clinical Protein Science & Imaging, Dept. of Clinical Sciences (Lund) and Department of Biomedical Engineering, Lund University, Lund, Sweden

. 3Pharmaceutics, Biomedical Research; 4Division for Technological Development, Center for Genetic Engineering and Biotechnology

luis.espinosa@cigb.edu.cu

A desalting step using reversed phase chromatography is a common practice previous mass spectrometry analysis of proteolytic digests despite that this is responsible for the non-detection of hydrophilic peptides. The detection of this kind of peptides is also important for full proteins sequence coverage, analysis of PTMs and quality control in recombinant proteins according to ICHQ6B guidelines. The procedure described here, named as in-solution buffer-free digestion (BFD), simplifies the sample processing and circumvents the above mentioned limitations by allowing direct ESI-MS analysis of tryptic hydrophilic peptides. Two DNA recombinant proteins such as HBcAg (Hepatitis B core Antigen) and fusion VEGF (Vascular Endothelial Growth Factor) were analyzed with the proposed in-solution BFD which resulted in the detection of extremely hydrophilic di-, tri- and tetra-peptides, C-terminal His-tag peptide, as well as disulfide-containing peptides which are hardly seen in mass spectrometric analysis using an standard digestion that includes a C18-desalting step. The procedure was also tested with success in the analysis of hydrophilic tetra- and hexa-peptides of RNase B (Ribonuclease B) carrying an N-glycosylation site occupied with “high-mannose” N-glycan chains. The in-solution BFD constitutes a simple and straightforward approach to analyze hydrophilic proteolytic peptides which are elusive to the detection by conventional mass spectrometric analysis.

In Silico Assessment of Potential Druggable Pockets on the Surface

of Nucleophosmin

Vieyto-Nuñez JC1, Guirola-Cruz O1, Perera-Negrin Y2

1.Bioinformatics group, Department of System Biology, Biomedical Research, Center for Genetic Engineering and Biotechnology

2Molecular Oncology Laboratory, Pharmaceutical Department, Biomedical Research, Center for Genetic Engineering and Biotechnology

jcvieyto@biocomp.cigb.edu.cu

Nucleophosmin (also known as NPM1, B23, No38, and Numatrin) is a multifunctional protein mainly localized at cellular nucleolus. NPM1 is highly important in ribosome maturation and export, centrosome duplication, cell cycle progression, histone assembly and response to a variety of stress stimulus. B23 is also frequently overexpressed in solid tumors and, in many cases, its overexpression correlates with mitotic index and metastatization. Therefore it is considered as a promising target for the treatment of both hematologic and solid malignancies. The physiologic structure of NPM1 is a pentameric ring with an N-terminal oligomerization domain taking part of a natural equilibrium between the pentameric structure and the monomer. The present work analyzed monomers molecular surface to predict druggability and maximal binding affinity sites on the protein; which ultimately may guide the development of NPM1 oligomerization inhibitors. Viable structural models of monomer peptide from NPM1 pentamer were obtained from the first steps using techniques of classical molecular dynamics (MD). Subsequently, the molecular surface area of a target protein was explored through Druggability suite (DruGUI) methodology, which was implemented by default variant and a modified one. Our results, as a quantitative estimate of binding sites and affinities for potential drug acting, suggest two important binding sites on the monomer molecular surface. The proposed methodology can contribute to assessing the druggability of protein targets and identifying allosteric or novel sites for drug binding; also allows designing a small molecule-like inhibitor.

In silico analysis of the interaction between the HLA II receptor

associated with Reumetoid Arthritis and altered peptide ligand.

Fundora, B1 Dominguez, M2 Guirola, O1

2Proteomics group, Department of System Biology, Biomedical Research, Center for Genetic Engineering and Biotechnology

brenda.fundora@cigb.edu.cu

Rheumatoid arthritis (RA) is a chronic, progressive and autoimmune disease that affects approximately 1% of the adult population worldwide. It is characterized by persistent inflammation of the synovial membrane; usually observe in peripheral joints, leading to cartilage destruction, bone erosion and joint deformity. Nowadays, the development of therapeutic variants that specifically eliminate pathogenic T cells, without causing a generalized immunosuppression, constitutes a challenge for the treatment of this disease. Therefore, the induction of peripheral tolerance through the use of autoantigens involved in the pathogenesis of RA constitutes an alternative for this purpose. The Hsp60 protein is one of this autoantigens In the Center for Genetic Engineering and Biotechnology have been designed the CIGB-814 peptide. It is an altered peptide ligands (APLs) using like model Hsp60 protein. It is known that for the activation of T cells these peptides must be presented to the T cell receptors (TCR) by the major histocompatibility complex (HLA in humans). For that, it is very important to known how the formation of the peptide-HLA complex at molecular level occurs.In this research, a theoretical study of the interaction between the HLA II molecules associated with AR and the CIGB-814 peptide has been carried out. The interaction of this receptor with the peptide analog derived from Hsp60 is also studied. The method that has been used is the molecular docking with the Rosetta program. This study allows obtaining a vision for the future design of new peptide candidates with immunogenic properties for this and other autoimmune diseases.

Impact of post-translational modifications on signaling pathways in

patients with lung cancer

Baez S1; Palomares S1; Guirola O1.

saiyet.baez@cigb.edu.cu

Lung cancer is one of the most common at present and the leading cause of death worldwide. The different post-translational modifications form a complex regulatory program that is fundamental for the normal development of the organism. Often the deregulation of these events is implicated in the development of numerous diseases, specifically in cancer. There is evidence to suggest that these abnormalities contribute to the development of lung cancer. Therefore, it is important to elucidate the regulatory mechanisms and the molecules involved. These molecules can serve as diagnostic, prognostic and predictive biomarkers for this disease. In the work, we described the main post-translational modifications for patients with lung cancer, the metabolic pathways, the molecular functions and the biological processes involved in these changes are analyzed. These modifications allow increase the migratory and invasive potential of the tumor cells. Besides it plays an important role in the tumor progression. Post-translational modifications also contribute to cell-cell contact and to the epithelial-mesenchymal transition in cancer cells.

Analysis of post-translational modifications in Acute Myeloid

Leukemia and their impact in the discovery of new biomarkers.

Palomares, S1; Guirola, O1; Gonzalez, LJ2

1Bioinformatics group, Department of System Biology, Biomedical Research, Center for Genetic Engineering and Biotechnology

2 Head of Department of System Biology, Biomedical Research, Center for Genetic Engineering and Biotechnology

sucel.palomares@cigb.edu.cu

Acute Myeloid Leukemia (AML) is a heterogeneous and aggressive malignant diseases of the hematopoietic system, with a high rates of relapse. In this context, a biomarker or biomarker panel will be useful in the diagnosis, prognosis, treatment selection and prediction of a resistant phenotype. A tumor biomarker is often describe as a molecule that can be measured and evaluated as an indicator of cancerous processes, with a certain degree of specificity. Lately, it has being reported the use of a pattern of post-translational mutations in a tumoral system, which better predictive results that the protein expression level. In this work we summarize the principal molecules described as potentials biomarkers associated with AML and their biological pathways and process, making a special emphasis in those presenting post-translational mutations. These modified proteins or their pattern of post-translational mutations could also lead us in the future to upstream or downstream targets or biomarkers in a molecular pathway relevant for this diseases.

Assessing the Impact and Cost Effectiveness of Free Comprehensive

Health Care and Financial Support in Rural Mexico”

Williamson AE, Ponce de Leon L, Macias V and Flores H.

Department of Economics, Oxford University; Harvard Medical School, Boston; Partners in Health Mexico, Jaltenango

There are now many sites where health interventions are promoted by philanthropic medical groups in economically disadvantaged places. Although the health benefits are obvious and can be quantified, it is more difficult to determine whether there are persistent economic benefits to the communities in which the health interventions occur. We will offer an analysis of whether economic benefits can be demonstrated for one such project in Mexico.

PARTICIPANTS LIST Adelaida Villareal Barrios

adelaida.villareal@cigb.edu.cu

Center for Genetic Engineering and Biotechnology, CIGB

Alberto Cintado Benitez

alberto.cintado@cigb.edu.cu

Amanda Beatriz Colarte Gonzalez

amanda.colarte@cigb.edu.cu

Andreas Werner

andreas.werner@newcastle.ac.uk

Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon

Tyne, United Kingdom

Bahk Won Myong

Chair of Department of Psychiatry, Yeouido St. Mary’s Hospital, College of Medicine,

The Catholic University of Korea, Seoul, Republic of Korea. Advisor and Past

President of Korean Society for Affective Disorders

Beatriz Mancheco Teruel

beatriz@infomed.sld.cu

National Center of Medical Genetics, Havana

Bjarne Udd

bjarne.udd@netikka.fi

Tampere Neuromuscular Center Helsinki University

Brenda de la Caridad Fundora

brenda.fundora@cigb.edu.cu

Caridad Sucel Palomares

sucel.palomares@cigb.edu.cu

Chottova Dvorakova M

Magdalena.dvorakova@lfp.cuni.cz

Dpt. of Physiology, and Biomedical Center, Faculty of Medicine in Pilsen, Charles

University

Dania Marcia Vazquez Blomquist

dania.vazquez@cigb.edu.cu

Daniel Octavio Palenzuela Gardon

daniel.palenzuela@cigb.edu.cu

Duk In Jon

jazzphilic@gmail.com

Professor Department of Psychiatry Hallym University Sacred Heart Hospital

Du Toit Loots, PhD

Dutoit.Loots@nwu.ac.za

Human Metabolomics, North-West University

Elianet Lorenzo

elianet.lorenzo@cigb.edu.cu

Eunsung Lim

calvaria0416@hanmail.net

Department of Psychiatry, Shinsegae Hospital, Kimje

Georg Auburger

auburger@em.uni-frankfurt.de

Exp. Neurology, Goethe University Frankfurt am Main

Gerardo E. Guillén

gerardo.guillen@cigb.edu.cu

Director of Biomedical Research at Center for Genetic Engineering and

Biotechnology, CIGB

Giselle Pentón-Rol

giselle.penton@cigb.edu.cu

Gleysin Cabrera

gleysin.cabrera@cigb.edu.cu

Hanlet Camacho Rodriguez

hanlet.camacho@cigb.edu.cu

James Kevin Hicks

James.Hicks@moffitt.org

Personalized Medicine Specialist, Department of Individualized Cancer

Management, Moffitt Cancer Center, Florida

Jeong Seok Seo

sjs52632@hanmail.net

Professor of Department of Psychiatry, Konkuk University hospital, Chung-Ju

Jong Hyun Jeong

anton3@catholic.ac.kr

Professor Department of Psychiatry St. Vincent's Hospital College of Medicine, The

Catholic University of Korea

Juan Roca Campaña

juan.roca@cigb.edu.cu

Julio Cesar Vieyto

julio.vieyto@cigb.edu.cu

Karel Lemr

Karel.Lemr@upol.cz

"Dept. of Analytical Chemistry – RCPTM Palacky University 17. listopadu 12, 771 46

Olomouc, Czech Republic

Karel Asael Barberena Morales

karel.asael@eti.biocubafarma.cu

Kewal K. Jain

jain@pharmabiotech.ch

Jain PharmaBiotech

Kwanghun Lee

nostre6@msn.com

Chair of Department of Psychiatry, Dongguk university hospital, Gyeongju, Republic

of Korea. President of Korean Society of Biological therapies in psychiatry

Laura de la Caridad Bakos Ruiz

laura.bakos@cigb.edu.cu

Lidia Inés Novoa Pérez

lidia.ines@cigb.edu.cu

Luis Almaguer Mederos

lalmaguermederos@gmail.com

Center for Research and Rehabilitation of Hereditary Ataxias. Holguin

Luis Ariel Espinosa

luis.espinoza@cigb.edu.cu

Luis Javier González

luis.javier@cigb.edu.cu

Luis Velázquez Pérez, PhD

luis.velazquez@infomed.sld.cu

Senior Academic of the Cuban Academy of Sciences President of the Cuban

Academy of Sciences

María Elena Fernández de Cossio

mariaelena.fernandez@cigb.edu.cu

Marisol Urrea

marisol.urrea@cigb.edu.cu

Masood Kamali Moghaddam

masood.kamali@igp.uu.se

Department of Immunology, Genetics and Pathology.Uppsala University.

Mauricio Quiñones

mauricio.quinones@cigb.edu.cu

Mayte Ale Martinez

mayte.ale@cigb.edu.cu

Mihalis I. Panagiotidis

m.panagiotidis@northumbria.ac.uk

Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria

University, Newcastle

Min Kyung Joon

kjoonmin@gmail.com

Professor / Chairman, Department of Psychiatry, Medical College, Chung-Ang

University. Director, Department of Psychiatry, Chung-Ang University Hospital

Moon Doo Kim

mdkim0721@gmail.com

Professor Department of Psychiatry, School of Medicine Jeju National University

Osmany Guirola

osmany.guirola@cigb.edu.cu

Patricia Sosa

patricia.sosa@cigb.edu.cu

Lee Sangyeol

psysangyeol@hanmail.net

Psychiatrist-in-Chief Wonkwang University School of Medicine, Iksan

Robert Williamson

r.williamson@unimelb.edu.au

Scientific Director, Yulgilbar Alzheimer¹s Research Program, Ex-Secretary for

Science Policy, Australian Academy of Science, Faculty of Medicine, University of

Melbourne

Satomy Pousa

satomy.pousa@cigb.edu.cu

Sayet de la Caridad Llovio

saiyet.baez@cigb.edu.cu

Sehoon Shim

shshim2k@daum.net

Chair of Department of Psychiatry, Soonchunhyang university hospital, College of

Medicine, Soonchunhyang University of Korea, Cheonan

Sergio Ponce Domínguez

Sohn Inki

fiveway@daum.net

Department of Psychiatry, Keyo Hospital, Uiwang city

Stanislav N.Naryzhny

snaryzhny@mail.ru

Petersburg Nuclear Physics Institute NRC "Kurchatov Institute", Leningrad district,

Gatchina

Susmita Datta

susmita.datta@ufl.edu

Professor, Co-Director of Biostatistics and Epidemiology Research Design (CTSI);

Tenured Professor and Preeminent Hire Department of Biostatistics; College of

Public Health & Health Professions and College of Medicine University of Florida

Suzana Gispert Sanchez

gispert-sanchez@em.uni-frankfurt.de

Experimental Neurology, Goethe University Medical School, Frankfurt

Tamara Diaz Argudin

tamara.diaz@cigb.edu.cu

Yanelda García

yaneldag@cim.sld.cu

Center of Molecular Immunology, Havana, Cuba

Yassel Ramos

yassel.ramos@cigb.edu.cu

Yoon Bo Hyun

yoonbh@chollian.net

Director, Department of Psychiatry, Naju National Hospital, Naju

Young Joon Kwon

alienist1@naver.com

Department of Psychiatry, Soonchunhyang University Cheonan Hospital, College of

Medicine, Soonchunhyang University, Cheonan

Vladimir Havlicek, PhD

vlhavlic@biomed.cas.cz

Institute of Microbiology Prague

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8th International Symposium on OMICS and...

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Cell Membrane. Hydrophilic Hydrophobic Hydrophilic.

Hydrophilic Versus Hydrophobic Microstructure Stictionee247b/sp14/... · Hydrophilic Versus Hydrophobic •Hydrophilic: ªA surface that invites wetting by water ªGet stiction ªOccurs

Omics Integration

Why Hydrophilic Coatings? · 2020. 10. 2. · synthetically. Once a hydrophilic surface is exposed to water or moisture, the hydrophilic surface grabs the water molecules and holds

Evaluation of Hydrophilic Properties of ...

Preparative Scale Chromatography of a Hydrophilic Peptide using … · 2014-09-04 · 1 Preparative Scale Chromatography of a Hydrophilic Peptide Using Hydrophilic Interaction Chromatography

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HPLC Column for Hydrophilic Interaction …...Comparison with C18 Columns HPLC Column for Hydrophilic Interaction COSMOSIL HILIC ・Triazole bonded stationary phase ・Enhanced hydrophilic

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New Hydrophilic Materials for SPE

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OMICS Group - OMICS Publishing Group · OMICS Group OMICS Group International through its Open Access Initiative is committed to make genuine and reliable contributions to the scientific

Hydrophilic Blended Additive - MDPI

Quantitative estimation of the hydrophilic- hydrophobic ... · Quantitative estimation of the hydrophilic- hydrophobic balance of ... culating the hydrophilic-hydrophobic balance

THE HYDROPHILIC, PROTEASE-SENSITIVE TERMINAL …

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Non Woven Hydrophilic

Hydrophobic Hydrophilic

Hydrophilic Waterstop — Bentonite-free

About OMICS Group OMICS Group International is an ... · About OMICS Group OMICS Group International is an amalgamation of Open Access publications and worldwide international science