International Conference and Exhibition on Molecular Medicine and Diagnostics August 24-26, 2015 West Drayton, London, UK

Biography:

Arkady Mustaev graduated from Novosibirsk State University (Russia). Received his PhD degree from Novosibirsk Institute of Bioorganic Chemistry. Postdoctoral training was at Irkutsk Limnological Institute, Moscow Institute of Molecular Genetics, Columbia University, and Public Health Research Institute of New York City. Presently he is Assistant Professor at PHRI Center, NJMS at Rutgers, the State University of New Jersey. He has published over 90 papers in reputed journals. The main research areas are: catalytic mechanisms of transcription, bacterial and cancer drug development, in vivo detection of human microbial pathogens, bioorganic chemistry and chemistry of natural compounds.

Abstract:

Invasive fungal infections (IFI) are a major threat to human health. In particular, medical advances in the management of cancer patients and hematopoietic stem cell and organ transplantation, in addition to immunocompromising diseases such as AIDS, have increased the population at risk for IFI. Successful treatment of fungal infections relies on unequivocal diagnosis and rapid response. In the case of mould infections due to Aspergillus species, diagnosis represents a significant challenge resulting in a mortality rate of around 85% for patients in Europe and the USA. For IFI detection we suggest the approach based on using high-affinity and high specificity labeled antifungal drugs as diagnostic molecules. As a result the fungal cells become labeled and therefore can be detected. The exceptional diagnostic ability of our compounds relies of their high binding constants to targets that are only present on fungi and are not present in the host. In our preliminary studies we successfully validated this approach by imaging fungal infections in vitro and in vivo in a murine model of candidiasis using fluorescently labeled drugs emitting in near-infrared spectral range, in which body tissues are transparent for excitation and emission light. The power of this approach is not limited to fungal infections, but in fact represents a broader platform useful for detection of other classes of human microbial pathogens.

Biography:

Peter L. Nagy received his MD degree from the University of Pecs, Hungary in 1989. He obtained his PHD at Purdue University in Biochemistry under the mentorship of Dr. Howard Zalkin and his Anatomic and Molecular Genetic Pathology training at Stanford University working on the MLL gene with Michael Cleary and Roger Kornberg. His research is on neurodegenerative disorders like ALS and young adult onset ataxias (AOA2). He built and oversees the clinical next-generation sequencing facility in the Laboratory of Personalized Genomic Medicine at Columbia University Medical Center.

Abstract:

Our Laboratory of Personalized Genomic Medicine (LPGM) at Columbia University Medical Center started to offer clinical whole exome sequencing (WES) in January 2013 and cancer whole exome/transcriptome (CWES) testing a year later. We processed and issued reports on over 500 constitutional cases and about 70 cancer cases. Next-generation sequencing in the clinical practice allows for a critical review of the literature describing the pathogenicity of specific mutations or the disease relatedness of specific genes and also provides an important discovery tool for new disease genes and disease causing mutations. Because of the large volume and complex nature of the data obtained from large panels and whole exome sequencing testing, the management of the data in a transparent, yet powerful analytical framework is key to a successful clinical operation. We have provided diagnosis for constitutional patients and information affecting clinical management for cancer patients in about one third of the cases we analyzed. The full potential for discovery of new disease associated genes and disease causing mutations can only be realized if there is a tight collaborative effort between the clinicians performing the interpretation and structural biologists and analytical chemists and cell biologists who can help predict and verify the effects of variants identified.

Biography:

Marisa Martin-Fernandez is Head of the Functional Biosystems Imaging Group, Central Laser Facility, Science & Technology Facilities Council, Dr Martin-Fernandez received a degree in Physics from the Autonomous University of Madrid, and her PhD in biophysics at the University of Keele. After several postdoctoral research appointments she was appointed Principal Scientist at the Science and Technology Research Council in 2002. She has run a research group since 2003 with a focus on developing novel instrumentation and methods to improve our understanding of cancer at the molecular level and to exploit these instruments to derive models of anti-cancer drug-induced behaviour.

Abstract:

Many new targeted therapies are currently in use, undergoing trials, or being developed as alternatives to conventional chemotherapy. The majority of these treatments are aimed at modifying the action of receptors located in the plasma membrane and involved in cell signalling, as mutations or overexpression of these receptors is linked with the development of a significant number of human cancers. However, only 30-70% of the patients respond positively to any particular type of drug. Moreover, the majority of patients undergoing targeted cancer therapy develop drug resistance, resulting in a relapse. Stratified medicine is an emerging field where the cancer patients are classified based on the presence or absence of underlying mutations to prescribe personalised treatment. We have developed a novel super-resolution microscopy based technology, and used this to show that mutations result in changes in the structure of clinically relevant protein complexes in cells, and that these structural changes can be altered or reversed through the application of targeted drugs. This should allow stratification of the patients based on variations in protein complex structure rather than the underlying mutations. This approach would provide targeted treatment of cancer patients as well as continuing assessment to monitor any development of drug resistance. Also, by providing a direct measurement of the effect of drugs on the structure of receptor complexes, this technique has the potential to rapidly identify effective new therapeutics.

Biography:

Born in 1940, graduated from the State Medical Institute in Lvov (Ukraina), took postgraduate course and thereafter received a PhD degree in Embryology in 1976. From 1966 till 1987 he was working at the Institute of Experimental Medicine RAMN (Saint-Petersburg) as a scientific collaborator at the Department of embryology and from 1980 in the Laboratory of biochemical genetics. From 1987 till the present time is the Chief of laboratory for prenatal diagnosis of inherited and inborn diseases at the Ott’s Institute of Obstetrics, Gynecology & Reproduction. Mainly interested in genetic and cytogenetic aspects of early human development, gene testing of inherited predisposition to common diseases, personalized predictive medicine, gene therapy. During the period of 1995-2009 he was awarded by A.A.Bayev Prize, Honorary Prizes from Russian Academy of Medical Sciences, I.P.Pavlov Prize, S.N.Davidenkov Prize. V.S.Baranov – is a chief City Expert in Medical Genetics, Chief of Federal Center for prenatal diagnosis of cystic fibrosis, Chief of Federal Medical Genetic Center, WHO expert on human genetics, Member of HUGO and Human Variome Project Consortium. Member of editorial boards of scientific journals “Medical Genetics”, “Prenatal Diagnosis”, “Ecological Genetics”, “Balkan J.Medical Genetics” The author of 29 books (1 in English “Cytogenetics of Mammalian Embryonic Development” Oxford University Press 1987,356pp) and over 400 scientific papers.

Abstract:

Endometriosis (E) is a common multigenetic disorder affecting almost 10% of women of reproductive age. Complex molecular, genetic, immunological analysis and endocrinology tests were applied in the studies of 257 women with E and in 117 women in the control Participation of the genes responsible for steroid hormone activity, their receptors, inflammation, proliferation, cell migration, apoptosis, intercellular adhesion, angiogenesis as well as the genes regulating their activity have been suggested as plausible candidates. A handful of very interesting new candidate genes involved in oncogenesis , metaplasia of endometrium cells and embryonic development of female reproductive system were identified by GWAS technology and also by conventional genetic testing. Genetic polymorphisms and differential expression of the candidate genes regulated by different epigenetic factors were thoroughly studied and substantiated complex epigenetic landscape of E . According to recent hypothesis ( Baranov et al,2015) E could be induced by different combinations of relevant genetic and epigenetic factors with subsequent canalization of pathological process , which soon becomes irreversible and inevitably proceeds to clinical manifestations following “ direct or reverse epigenetic landscapes” routs. Two hypothetical stages of E include: the origin of primary incipient endometrioitic cells (PIEC) resulting as transition products of emdometrial epithelia to mesenchymal cells ( metaplasia), as well as from vestigial embryonic or dormant stem cells (St 1) ; progression of PIEC into E. lesions augmented by numerous genetic and epigenetic factors ( St.2) . Identification PIEC cells and complex molecular genetic analysis of their origin and progression may be fruitful in diagnostic biomarker search and may substantiate further advancement of prediction, prevention and treatment of E .

Biography:

Martin Flück is the Professor for Muscle Plasticity located at the Balgrist Hospital of the University of Zurich. His research centers on the adaptive pathways governing skeletal muscle function with specific focus on an integrative omics approach. He has published over 70 articles in peer reviews journal (H-index>24) and has served as an editorial board member of repute.

Abstract:

Hypoperfusion of skeletal muscle due to resistance to insulin-mediated vasodilation is an early hallmark of a cluster of metabolic diseases that represent a major economic substrate for the medical industry. Absence of an insertion sequence (the I-allele) in the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is associated with reduced aerobic fitness and the development of type 2 diabetes. Our investigations identify out of norm elevations in serum glucose concentration after the metabolic challenge of exhaustive endurance exercise in ACE-DD genotypes that do not carry the ACE I-allele. Explorative assessment of the muscle metabolome and transcriptome exposed that the defect involves a reduced oxidation of glucose and compensatory adjustments in mitochondria-associated pyruvate and amino acid metabolism; all of which corresponded to a reduced muscle capillarisation and elevated serum levels of the ACE product, angiotensin 2. Compared to ACE-II genotypes, ACE-DD genotypes had a lower capacity for oxygen extraction during exhaustive exercise and the subsequent response in mitochondrial biogenesis was blunted. Anti-hypertensive treatment with ACE inhibitor pronouncedly modulated mitochondrial and angiogenic gene expression in exercised muscle. Our observations imply that the monitoring of glucose import and combustion in working muscle exposes the genetic risk of developing metabolic disease.

Biography:

I have an international professional standing and research expertise to enhance clinical interventions in Barrett\'s oesophagus and oesophageal cancer. I am a member of the BSG/National Clinical Research Institute Upper GI early cancer prevention research subgroup. I am a peer reviewer for the NIHR RFPB programme and a member of the Research Steering Board of Manchester Cancer Research Centre (Cancer Research UK Manchester Institute). These research initiatives have shaped my contribution for the management of GORD, Barrett’s oesophagus and oesophageal cancer. I have published over 45 articles and I am a supervisor for PhD and MD students in the molecular cancer group of the University of Manchester.

Abstract:

Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. Their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several solid tumours. We have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in oesophageal adenocarcinomas and determined their role in oesophageal adenocarcinoma cell function. PEA3 plays an important role in controlling both the proliferation and invasive properties of OE33 oesophageal adenocarcinoma cells. A key target gene is MMP-1. The ERK MAP kinase pathway activates PEA3 subfamily members and also plays a role in these PEA3 controlled events, establishing the ERK-PEA3-MMP-1 axis as important in OE33 cells. PEA3 subfamily members are upregulated in human adenocarcinomas and expression correlates with MMP-1 expression and late stage metastatic disease. Enhanced ERK signaling is also more prevalent in late stage oesophageal adenocarcinomas. This study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas.

Biography:

Abstract:

We analyzed the glycine-rich secreted peptides (GRSPs) of 10 species genomes: Homo sapiens, Dani rerio, Drosophila melanogaster, Caenorhabditis elegans, Caenorhabditis briggsae, Arabidopsis thaliana, Monosiga brevicollis, Saccharomyces cerevisiae, Dictyostelium discoideum, and Guillardia theta. The number of Grsps in each genome was 4, 6, 53, 93, 78, 52, 0, 0, 5 and 0, respectively. Interestingly, there were fewer Grsps in human genome than in D. discoideum genome, despite the greater complexity of humans. The two nematode species C. elegans and C. briggsae possessed the highest abundance of Grsps, of which 98.7% were orthologous. Mapping these Grsps strengthened clustering and illustrated the clear co-linearity between the chromosomes of the two nematodes. In particular, most of Grsps were found on chromosome V: 44 of 93 C. elegans and 41 of 78 C. briggsae. A comparative analysis of orthologous Grsps from other species resulted in the successful annotation of 17 C. elegans Grsps with DAVID and 21 C. elegans and 3 C. briggsae Grsps with Blast2Go. This observation highlighted the nematode-specific expansion of Grsps originating from tandem duplications during ecological adaptation of the two nematodes. The phenomenon goes against the general rule that gene families also experience evolutionary expansion in abundance in increasingly complex species.

Biography:

Jurgen Dittmer has completed his PhD from University Bremen (Germany) and postdoctoral studies from the University of Zürich (Switzerland), the National Institutes of Health (USA) and the University of Tübingen (Germany). He is head of the research laboratory in the Clinic for Gynecology at the University of Halle (Germany) and is currently secretary of the EORTC Pathobiology Group. He has published more than 50 papers in reputed journals and has been serving as an editorial board member of BMC Molecular Biology and BMC Research Notes.

Abstract:

Cancer lesions are complex organ-like tissues that are not only composed of a heterogenous population of cancer cells but also of different types of stromal cells. The tumor stroma is not a bystander, but heavily involved in tumor progression and therapy resistance. Stroma-mediated drug resistance is a new challenge and needs to be considered in therapy decisions. However, we have just begun to understand the mechanisms underlying stroma-mediated drug resistance. The acquisition of such resistance requires the interaction between the tumor cells and the stroma which is supposedly quite complex given the different types of stroma cells and the heterogeneity within the cancer cell population. Hence, the outcome of such interactions in terms of drug resistance may vary depending on the particular cells involved. To address this issue, we are analyzing the effects of different stromal cells on a variety of subtypes of breast cancers and on different subclones residing in a heterogenous breast cancer cell population.

Biography:

Professor Janak Kishore, graduated in medicine in 1978, did M.D. in 1985 and is now Chief of Molecular Virology and Serology Divisions. He was Associate Editor Indian Journal of Virology, member National Academy Medical Sciences, American Society for Virology, Fellow of JICA, Japan. Dr Kishore taught for over 30 yrs and published over 50 papers. His pioneer work on B19 bagged many award owing to publication of three novel clinical associations and possible Oncolytic property of B19. Dr Kishore, served as reviewer for reputed journals, organized conferences, Chaired sessions and frequently invited to speak at international conferences.

Abstract:

Parvovirus B19 (B19), (discovered 1975) listed as newly emerging virus (1981-1987) but could not gain importance due to asymptomatic/self-limiting infections, myriads of clinical afflictions not known to many clinicians, limited diagnostic facilities, unknown disease burden and sinister complications. Hence in-house diagnostic methods of DNA extraction from serum, PCR, nested-PCR, IgM and IgG ELISA were standardised. Seroprevalence of B19 was found to be 39.9% among 1000 blood donors i.e. 60% of Indian population (1.2 billion) at risk of B19. We published fatal cases of B19 induced pure red cell aplasia, thrombocytopenia with hepatitis and hemophagocytic syndrome. B19 infections were unveiled by us in 27.5% arthropathy (n=69), 19.8% recurrent aborters (n=116), 60% high-risk pregnant women (n=60), 17.1% paediatric haematological malignancies (n=35) and 41% beta-thalassemia major (n=90). Novel clinical associations like amegakaryocytic thrombocytopenia ,myositis as a complication of erythema infectiosum and recently non-occlusive ischemic gangrene of stomach and bowel were reported. Our limited work denotes high/alarming situation of B19 infections, hence B19 be looked/recognised and prevented by a licensed B19 vaccine.

Biography:

Laura Hill is a Senior Scientist in the Design and Development department at QIAGEN Manchester, UK. She has significant experience of companion diagnostic development, specialising in primer and multiplex assay design, feasibility studies and novel technologies. She previously worked at Life Technologies on the development and manufacture of primer mixes for DNA testing kits. She has a degree in Genetics from the University of Liverpool

Abstract:

The ModaplexTM system is a fully automated platform that combines a real time PCR module with a capillary electrophoresis detection module. The combination of these two modules allows for a large number of targets to be detected in a single reaction. Multiplexing systems that allow such a broad range of targets to be detected are desirable in companion diagnostic assays; to reduce intrusive procedures to patients, by requiring less sample material, and to reduce laboratory processing time. To investigate how the ModaplexTM system can make use of these benefits, we have undertaken a feasibility study to combine the detection of 42 mutation targets and 2 control targets in a single reaction. Gene panels comprising of 13 KRAS mutation targets and 29 EGFR mutation targets are the focus of this multiplexing challenge. EGFR and KRAS are key molecules in the MAPK cellular signaling pathway. Since mutations in these genes alter cellular functions, determining the mutation status is a key requirement for personalised cancer therapies. The primer designs for the 44-plex assay have initially been tested using synthetic oligonucleotides and will be further challenged with the use of FFPE extracted clinical samples. This feasibility study will demonstrate the multiplexing capabilities of the ModaplexTM system to meet the growing market need for quicker, less intrusive mutation detection.

Biography:

After a degree in Chemistry from Oxford University, UK, Margaret Wheatley completed her PhD in Chemical Engineering at the University of Toronto and postdoctoral studies at MIT, Cambridge MA, USA. She holds the John M. Reid chair of Biomedical Engineering at Drexel University in the School of Biomedical Engineering, Science and Health Systems. She has published more than 100 papers in areas of imaging, drug delivery and spinal cord repair.

Abstract:

Hypoxia in tumors inhibits sensitivity to radiation therapy. We studied the delivery of oxygen to tumors using an ultrasound-sensitive microbubble platform developed at Drexel consisting of a mixed surfactant shell surrounding either oxygen (SE61O2) or nitrogen (SE61N2). Oxygen release kinetics were measured using an Oxy Lite 2000 bare fiber pO2 probe. In vitro ultrasound used a Sonix RP scanner with a PA4-2 probe in power Doppler mode. Samples in 100 ml degassed saline were triggered over 20 minutes (readings obtained every 30s). In vivo proof of concept (two mice with MDA-MB-231 breast tumor xenografts) introduced the probe into the tumor via 21G catheter. Flash-replenishment imaging at the fiber tip was performed using a Vevo 2100 scanner in nonlinear imaging mode at 18 MHz during IV injection of 0.05 ml of agent. Partial oxygen pressures were recorded every 5s until returned to baseline. Release profiles were compared to untriggered SE61O2, and triggered SE61N2. Two ml of SE61O2 triggered with ultrasound elevated oxygen partial pressures of 100 ml of degassed saline 13.8 mmHg more than untriggered bubbles and 20.6 mmHg more than triggered nitrogen-filled bubbles. In vivo controls produced no discernible increase in oxygen partial pressure except for a brief (25s) 5.6 mmHg increase in one animal. Ultrasound triggered SE61O2 resulted in a 30.4 mmHg increase in one tumor, with elevated tumor oxygen levels lasting over 4 minutes, and an increase of 27.4 mmHg, with elevated tumor oxygen levels lasting 1.7 minutes in the second. We conclude that in vivo elevation of tumor oxygenation levels using SE61O2 appears feasible but highly tumor dependent.

Biography:

Katrin Beyer has completed her PhD in molecular biology at the Autonomous University of Barcelona and has worked for 20 years in dementia research. Recently, she focused on the molecular characterization and biomarker search for the early and differential diagnosis of dementia with Lewy bodies. She has requested four patents during the past five years, has published more than 35 papers in reputed journals, and has been serving as an editorial board member of repute and peer reviewer for more than 20 biomedical journals.

Abstract:

Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are synucleinopathies and DLB is the most frequent cause of dementia after Alzheimer’s diseases (AD). All three show an important neuropathological overlap and especially DLB is difficult to diagnose. DLB results from complex interactions among different susceptibility genes and environmental risk factors with particular impact for each individual. Although all patients fulfill diagnostic criteria fitting within certain spectrum of symptoms and disease course, the primary cause of DLB may not be the same in all cases. So far, alpha-synuclein pathology caused by alpha-synuclein oligomerization and further aggregation, and cholinergic deficit that is even more pronounced in DLB than in AD brains, have been unequivocally involved in DLB pathogenesis. But even these main pathologic processes reach different degrees of severity in each patient and are accompanied by other pathological events. Similar severity degrees of the various processes define molecular subgroups of DLB, and these are detectable independently each one by its own biomarkers. We have recently described two molecular subgroups of DLB. One of them comprises about 30% of all patients and is characterized by the absence of beta-synuclein in cortical regions. The other constitutes around 10% with cortical butyrylcholinesterase diminution. For both molecular defects we have identified the associated genetic biomarkers useful for the early detection of these patients. Our results also indicate that DLB can develop as primary or secondary synucleinopathy. In the latter, alpha-synuclein pathology would develop after action of primary alterations such as lysosomal dysfunction or transcriptional deregulation.

Biography:

Jeng-Long Hsieh had completed her Master degree from Rutgers University in United States and PhD degree from National Cheng Kung University Medical College in Taiwan. She is a former Dean of College of Medicine and Life Science, Chung Hwa University of Medical Technology, and now a professor in the Department of Nursing. Her research focus on two fields, cancer gene therapy and molecular factors in bone related diseases. She has published 20 papers in reputed journals and has been serving as a reviewer of repute.

Abstract:

De Quervain’s disease, or stenosing tenosynovitis of the first dorsal compartment of the wrist, is a common ailment. How estrogen is involved in this disease is not clear. We previously showed that inflammation was involved in the pathogenesis of de Quervain’s disease. In this study, the expression of estrogen receptor (ER)- is further examined to delineate the possible roles of estrogen in this disease. Postoperative retinaculum samples were collected from 16 patients with de Quervain’s disease. The specimens were histologically graded by collagen structure. They were immunohistochemically evaluated by quantifying the expression of ER-, interleukin (IL)-1, IL-6, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF), and Von Willebrand’s factor (vWF). De Quervain’s disease occurs primarily in women. The female:male ratio in our study was 7:1. ER- was detected in the retinaculum and its expression increased with the grade of the disease and the age of the patient. Moreover, disease severity was related to the inflammatory cytokines IL-1 and IL-6, the inflammatory enzyme COX-2, and the angiogenic factors VEGF and vWF in the tenosynovial tissue. The severity of de Quervain’s disease is associated with increased ER- expression, tissue inflammation, and angiogenesis. ER- might be a useful target for treating de Quervain’s disease.

Biography:

After getting the PhD degree of Pathology and Pathophysiology in Shantou University Medical College (SUMC), China, Dr. Ting Long serves as an associate professor in Department of Physiology at SUMC. He dedicates in diabetes associated male sexual dysfunction studies investigating the mechanism of diabetic erectile dysfunction and sexual behavior disorder. There were several TNF-α related publication recently which suggests that TNF-α is both a significant molecular biomarker and highly potential target in diabetes associated male sexual disorder.

Abstract:

Background: Sexual dysfunction, including decreased libido, sexual behavior disorder and erectile dysfunction (ED), is common in male patients with diabetes mellitus (DM). We previously demonstrated that increased peripheral tumor necrosis factor alpha (TNF-α) expression, associated with inflammation in DM, contributes to ED in the rat corpus cavernosum. However, the role of TNF-α in the central pathophysiology of DM-associated male sexual dysfunction is unknown. In this study, we examined the effects of TNF-α inhibition, i.e. etanercept (ETN) via chronic intra-cerebroventricular (ICV) infusion on nNOS expression in the hypothalamic paraventricular nucleus (PVN) and sexual behavior disorder in male diabetic rats.
Results: Male diabetic rats with ICV aCSF treatment displayed significantly severe sexual disorder accompanied with blunted nNOS expression and activity in the PVN in addition to local upregulated TNF-α and TNFR-1 expression, and increased ROS generation compared with non-diabetic controls. The sexual behavioral parameters were significantly improved in the treated group with ETN. ICV ETN significantly inhibited TNF-α and TNFR-1 expression and reduced ROS generation in the PVN in diabetic rats. In addition, ICV ETN appeared to induce marked increased in nNOS expression in the PVN of diabetic animals compared with ICV aCSF-treated diabetic rats.
Conclusion: Increased TNF-α and TNFR1 expression in the hypothalamic PVN associated with DM contributes to male sexual disorder by centrally inhibiting nNOS expression and activity in the PVN via promoting local ROS generation. Central TNF-α blockade may have beneficial effects on the male sexual disorder in diabetes through improvement of NO pathway within the PVN.

Biography:

Jinwei Du has completed his PhD at the age of 27 years from Peking University and postdoctoral studies from Case Western Reserve University School of Medicine. He is the Vice President of R&D at Shanghai Tissuebank Biotech. He has published more than 20 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Alleles at the D7S820 STR locus have 6–14 different numbers of a four-nucleotide (GATA) repeat motif arranged in tandem. The D7S820 tri-allelic pattern is rare and has not been reported in the Chinese population. In this study we report a three-banded pattern at the D7S820 locus observed in a Chinese family, in which four family members in two generations had tri-allelic D7S820 genotype 10-11-12 and one family member had an abnormal bi-allele genotype 10– 11. All of the four tri-allelic cases had the genotype 10-11-12, probably due to three copies of the D7S820 STR sequence in all cells (Type 2 tri-allelic pattern), and deduced alleles 10–11 were a linked inheritance in this family.

Biography:

Xiaolin Lu has completed her MM at the Capital Institute of Pediatrics in 2007, and became a young researcher at Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics.The main work of her research is about the interaction of genetics and epigenetics in the mechanism of birth defects. Since 2013, she has published about 2 articles on genetic and epigenetic alternations in birth defects as the first author and joint first author.

Abstract:

SHH signaling pathway played an important role in the formation of dorsal ventral neural plate. It has been shown in mice that genes of SHH signaling pathway mutations increased the incidence of NTDs, such as spina bifida and brain anomalies. Moreover, the single nucleotide polymorphisms (SNPs) of several key genes belonging to SHH pathway have been verified to increase the risk of NTDs in our previous studies. GLI2 is a key mediator of the Sonic hedgehog (Shh) signaling pathway and plays an important role in neural tube development during vertebrate embryogenesis; however, the role of gli2 in human folate-related neural tube defects remains unclear. In this study, we compared the methylation status and polymorphisms of gli2 between spina bifida patients and a control group to explore the underlying mechanisms related to folate deficiency in spina bifida. No single nucleotide polymorphism was distributed significantly differently between the two groups, although gli2 methylation levels were significantly increased in spina bifida samples, accompanied by aberrant GLI2 expression. Moreover, a significant negative correlation was found between the folate level of brain tissue and the gli2 methylation status (r=−0.41, P=0.014), while gli2 hypermethylation increased the risk of spina bifida with an odds ratio of 12.45 (95% confidence interval: 2.71–57.22, P=0.001). We also used a cell model to illustrate the effect of gli2 expression and the accessibility of chromatin affected by methylation. High gli2 and gli1 mRNA expression was detected in 5-Aza-treated cells, while gli2 hypermethylation resulted in chromatin inaccessibility and a reduced association with nuclear proteins containing transcriptional factors. More meaningful to the pathway, the effect gene of the Shh pathway, gli1, was found to have less expression along with decreased expression of gli2 in the cell model. Aberrant high methylation resulted in the low expression of gli2 in spina bifida, which was affected by the change in chromatin status and the capacity of transcription factor binding.

Biography:

Lei Shang has completed his PhD at the age of 28 years from Central South University. He is the research worker of Hunan Cancer Hospital in the department of Translational Medicine Research, a premier Cancer Research Institute in Central South Region of China. He has published more than 10 papers in reputed journals.

Abstract:

Necroptosis is an important neuronal death mode in retinal ischemia, but the mechanism still needs clarify. RIP3 is characterized as an N-terminal Serine/Threonine kinase, which participates in cell death signaling. Previous studies indicated RIP3 may participate in neuronal necroptosis, and the activation of caspase-8 could cleave RIP3 to inactive form. In the present study, we explored the effects of RIP3 in retinal necroptosis following elevated hydrostatic pressure (EHP) and discussed the possible role of caspase-8 on regulation of RIP3 activity. Necrosis levels detection were repeated with pretreatment of Nec-1 of 24h to confirm the existence of necroptosis. The expression of RIP3, downstream molecules in the pathway of RIP3-induced necroptosis and necrosis levels of RGC-5 cells were detected by immunoblotting, immunofluorescence and flow cytometry at 6h, 12h or 24h after EHP. Then, RNAi to rip3 was used for further confirming RIP3’s effects on retinal necroptosis. Finally, caspase-8 inhibitor and activity peptide were applied to try to unveil the regulated mechanism of RIP3 activity. The results showed that, RIP3 expression was up-regulated and RIP3 enhance-labeled cells were coexisted with PI-positive cells after injury. PI-positive cells were reduced and ratios of necrosis were decreased after injury when treating with Nec-1and rip3 RNAi. The ROS and PYGL levels in pathway of RIP3-induced necroptosis had been found to be decreased after rip3 knockdown. Caspase-8 inhibitor and activity peptide usage affected ratio of necrosis and levels of ROS or PYGL. Our results indicated RIP3 participated in RGC-5 necroptosis following EHP and caspase-8 may interference RIP3-induced necroptosis. This work was supported by the National Natural Science Foundation of China (No.81070729), and National Key Technologies Research and Development Program of China(No. 2012BAK14B03) .

Biography:

F. Bandarian has completed his MD degree at the age of 27 years from Tehran University of Medical Sciences and completed PhD at Shahid Beheshti University Medicine Sciences in 2013. She is the Research Assistant of Diabetes Research Center at Tehran University of Medical Sciences. She has published more than 30 papers in reputed journals and has been serving as section editor of Journal of Dibetes and Metabolic Disorders.

Abstract:

Metabolic Syndrome (MetS) increases the risk for cardiovascular disease and diabetes. This study aim was to investigate the association between APOA1 polymorphisms and MetS in an Iranian population. Thirty-seven patients with MetS and 94 healthy controls were selected randomly from the population of Tehran Lipid and Glucose Study. Variant was identified by direct sequencing. The mean age of participants in MetS and control groups was 44.76±14.25 and 38.74±15.37, respectively. Frequency of mutant allele in MetS group was 1.35% while its frequency in control group was 13.8%. There was a significant association between rs201148448 and MetS. Also, there was a significant association between rs201148448 and serum triglyceride and HDL concentration as well as BMI and waist circumference (p=0.001). APOA1 variants rs201148448 contribute in MetS phenotype and protect against it in Iranian population. In relation to MetS, variants in other variants of APOA1 gene should be studied in future.

Biography:

Ievgeniia Burlaka is is a Professor in the Department of Pediatrics in National O O Bogomolets Medical University, Ukraine.

Abstract:

Proteinuria not only is a sign of kidney damage, but also is involved in the progression of renal diseases as an independent pathologic factor. Clinically, glomerular proteinuria is the most commonly observed, which relates to structural and functional anomalies in the glomerular filtration barrier. The objective of this project was to study the markers of apoptosis in kidney tissue in children with chronic glomerular diseases. 32 patients aged 5-18 years with an active stage of nephrotic syndrome were included to the study. Immunohistochemical examination of proapoptotic factor Bax, antiapoptotic factor Bcl-xL levels, apoptosis evaluation in kidney biopsy specimens was done. Analysis of the level of proapoptotic factor Bax in kidney slices obtained from children with morphological form focal segmental glomerulosclerosis (FSGS) showed the presence of high levels of Bax in both glomerular and tubular-interstitial segments. However, higher imunosignal was recorded in glomeruli with FSGS I-II st. compared to tubular segment. When complete glomerular sclerosis observed high levels of Bax were observed in the surrounding tubuli and interstitial segment. In kidney tissue from nephrotic patients the presence of a certain level Bcl-xL in both glomeruli, tubuli and interstitium was found. Higher imunosignal was recorded in tubuli, interstitial segment compared to glomeruli with FSGS I-II st. When complete glomerular sclerosis occures relatively high imunosignal of Bcl-xL is localized in the surrounding tubuli, interstitial segment with the almost complete absence in glomeruli. Quantitative analysis of apoptosis levels in kidney sections of patients with nephrotic syndrome and FSGS I-II st. revealed apoptotic index (AI) in glomeruli at level 21,5 ± 0,9%, in the tubuli and interstitial component - 9,12 ± 0,34% (p˂0,01). With FSGS III-IV st. high AI was found in tubuli, interstitial component - 31,22 ± 1,14%, in the glomeruli - 4,15 ± 0,6% (p˂0,001). Thus, progression of glomerulosclerosis as an irreversible kidney damage induced by chronic albuminuria is associated with increased activity of proapoptotic factor Bax and simultaneous reduction of anti-apoptotic factor Bcl-xL. The manner of Bax and Bcl-xL distribution in relation to the stages of FSGS is an indicator of step-dependent manner of glomerular and interstitial injuries development under the influence of proteinuria.

Biography:

N’Guessan Kouassi Raymond, is working in Institut Pasteur in Côte d'Ivoire, National Laboratory of Tuberculosis Reference. He also worked as Pneumology Service CHU de Cocody and National Programme against Tuberculosis.

Abstract:

Tuberculosis is explicitly recognized as a major global public health problem. In Côte d'Ivoire, relapse cases represent 66.5% of patients eligible for retreatment according to the National Tuberclosis Control Program. This study objective was to detect multidrug-resistance tuberculosis among relapse cases. Patients were recruited in tuberculosis centres in routine. A standardized questioning was administrated. Two sputum samples were collected and transported at Institut Pasteur. Sputum samples were decontaminated by NALC method. The DNA extraction was realized with 500µl of decontaminated sputum sample with smear-positive. MTBDRplus assay version 2.0 was performed according to the manufacturer’s instruction. An internal quality control program with positive and negative controls was implemented for interpretation of results. In total 146 relapse cases with smear positive were studied. Out of selected patients,130 had received the 2RHZE/4RH regimen and 16, the 2RHZES/1RHZE/5HRE. In group of relapse cases previously treated with 2RHZE/4RH regimen,40 (31.3%, IC95% : [0.23 ; 0.39]) had punctual mutations at codon 526 in rpoB gene. Although, in patients under treated with 2RHZES/1RHZE/5HRE, a mutation in rpoB gene was identified in 12 of 16 sputum samples. Thirteen mutations conferring a resistance to Isoniazid were observed of which 9 in katG gene and 4 in katG and promoter region of inhA gene. The comparison (Chi-square with Yates correction) of resistance rates to Rifampin estimated showed a statistically significant difference.

Biography:

Abstract:

The advancement in hepatitis C virus therapeutics has profoundly enhanced by an improved understanding of viral life cycle in host cells, development of novel direct-acting antivirals and exploring the other emerging treatment paradigms on the horizon. The approvals of first and second-generation direct-acting antivirals highlight the swift pace of progress in the successful development of an expending variety of therapeutic strategies for use in patients with chronic hepatitis C virus infection. Triple and quadruple therapies based on the combination of different direct-acting antivirals with or without pegylated interferon and ribavirin have raised the hopes to improve the current treatment strategies for other difficult-to-treat individuals. All-oral interferon free therapeutic regimens directed against hepatitis C virus infection are shown to be highly effective in the entire spectrum of patient populations, including the previously difficult-to-treat “special” situations. These revolutionary drug strategies now incorporate a cocktail of agents blended to take advantage of synergistic mechanism of action. The development of more efficacious, well tolerated, and cost effective interferons with low frequency of adverse events and short treatment durations are also in the pipeline. An experimental protective vaccine against hepatitis C virus demonstrated promise in preliminary human safety trials, and a larger phase II clinical trials are under consideration to further determine the efficacy of the vaccine. This review article describes the current state of knowledge in hepatitis C virus therapeutics, insights the potential pitfalls of current therapies, and provides a conceptual framework of emerging and investigational treatment strategies directed against hepatitis C virus.

Biography:

David Meridor has completed his Master degree and PhD degree in Chemistry from Bar-Ilan University in Israel, after publishing 4 papers. In the current position as a postocdorate researcher at Ben-Gurion University, he was involved in a project that entails synthesis of humanin derivatives, cell culture as well as in vivo studies in a model of traumatic brain injury.

Abstract:

Humanin is a 24-amino acid peptide known for its anti-apoptotic activity, especially against neuronal cell death caused by Alzheimer insults. Herein, we show a novel function of humanin and its derivatives, namely protection against necrosis, demonstrated both in vitro and in vivo. The synthesis of humanin is difficult due to hydrophobic amino acids that impose aggregation on the resin. Solid-phase peptide synthesis of humanin and its three derivatives, AGA-HNG, HNG and HN17 gave low yields.
In order to avoid aggregation and overcome difficult sequences couplings, we developed efficient synthetic procedures that are based on fragment condensation in solution. Furthermore, native chemical ligation was applied to overcome resin aggregation for synthesis of peptides that contain cysteine.
We found that humanin and its derivatives conferred protection in PC-12 and NSC34 cell lines in which necrosis was induced in glucose free medium by either chemohypoxia or upon staurosporine/oligomycin-A treatment. Moreover, in-vivo protective effect was shown in traumatic brain injury model in mice, where necrosis is the main mode of the neuronal cell death. We show that humanin derivatives antagonize the decrease in ATP levels associated with necrosis and also directly enhance the activity of isolated ATP synthase complex, indicating that humanin derivatives target the mitochondria, regulating ATP levels. The present findings could provide new therapeutic protocols for treatment of brain ischemic states, such as stroke, and traumatic brain injury, conditions for which no efficient drug-based treatment is currently available.