Program Day 1

Abstract:
To characterize the pathobiology of solar lentigos (SLs), analyses by semiquantitative RT-PCR, Western blotting, and immunohistochemistry revealed the upregulated expression of endothelin (EDN)-1/endothelin B receptors (EDNBRs), stem cell factor (SCF)/c-KIT, and tumor necrosis factor (TNF)α in the lesional epidermis, which contrasted with the downregulated expression of interleukin (IL) 1α. These findings strongly support the hypothesis that previous repeated UVB exposure triggers keratinocytes to continuously produce TNFα. TNFα then stimulates the secretion of EDNs and the production of SCF in an autocrine fashion, leading to the continuous melanogenic activation of neighboring melanocytes, which causes SLs. A clinical study of 36 patients with SLs for six months treated with an M. Chamomilla extract with a potent ability to abrogate the EDN1-induced increase in DNA synthesis and melanization of human melanocytes in culture revealed a significant improvement in pigment scores and color differences expressed as L values. Another clinical study using a tyrosinase inhibitor L-ascorbate-2-phosphate 3 Na (ASP) demonstrated that L values of test lotion (6% APS)-treated skin significantly increased in SLs and in non-lesional skin with a significantly higher ΔL value in SLs when compared with non-lesional skin. The sum of these findings strongly suggests that combined topical treatment with EDN signaling blockers and tyrosinase inhibitors is a desirable therapeutic choice for SLs.
Biography:
Dr. Genji Imokawa (Ph.D.-medicine) now is Professor of Utsunomiya University, Center for Bioscience Research and Education as well as Visiting Professor of Chubu University, Research Institute of Biological Functions and of Ohio University, Edison Biotechnology Institute. Board of Directors in Japanese Society for Ceramide Research and Japanese Medical Society for Skin Aging and Council member for Japanese Medical Society for Anti-Aging. His Research Activities: More than　175 original English papers including EMBO Journal, J Clinical Invest, J Cell Sci, Cancer Res, Am J Pathol, FASEB J, J Biol Chem, J Pathol and J Lipid Res; Research Field: Photo-aging/ Fibroblasts, Atopic Dermatitis/Sphingolipid Metabolism, Melanogenesis/Melanocyte Biology, Keratinization/Keratinocyte Biology.

Abstract:
SELEX technique is employed to select aptamers against wide range of targets. The in vitro method of aptamer selection using live cells as the target is referred as CELL-SELEX. The use of aptamers as therapeutic and diagnostic agents is rapidly evolving, selection techniques such as Cell-SELEX could be beneficial in identifying aptamers when the target is in its native conformation and without prior information of the cognate target, thereby bringing the aptamer development one step closer to the clinic. The presentation provides a comprehensive description on the development of aptamers through various cell-SELEX methods. In addition, it pinpoints the advantages and limitations of the cell-SELEX process and its variants. The given information can be valuable for the design and development of futuristic oligonucleotide based diagnostics and therapeutics work.
Biography:
Dr.Harleen Kaur has been in the pharmaceutical industry for almost 8 years and most recently led the analytics and drug product tech transfer projects for two biologics products while working at AstraZeneca, USA. Prior to this, she worked in R&D division of Fujitsu Asia Pte Ltd in Singapore where she worked on aptamer development and played an integral role in identifying and purifying aptamers against different protein targets in collaboration with National University of Singapore, Agency of Science Technology and Research Singapore, and Japanese diagnostic enterprise Sysmex. In her current role, she is leading a team of analytical scientists at Aurobindo Biologics and her responsibilities include the method development, method qualification and method transfer for different biosimilar products. she completed her PhD in chemical and biomolecular engineering department at National University of Singapore.

Abstract:
Multiple sclerosis (MS) is a chronic disorder characterized by multifocal inflammatory infiltrates (T cells, B cells, macrophages) within the central nervous system (CNS) and concomitant degradation of myelin, oligodendrocytes and axons, along with reactive microgliosis. Disease background is thought to include two overlapping processes: polyphasic myelin destruction (inflammatory demyelination) and progressive axonopathy (neurodegeneration) with little capacity for repair. The pathology is generally believed to reflect autoimmune attack upon myelin auto-antigens but the mechanisms resulting in the escalation of the autoimmune response and leading to the damage of white and gray matter in the CNS have not been so far fully clarified.
Lipid antigens are substantial myelin components and they also may constitute potential candidates for autoimmune attack in MS. We have recently explored the seem to be role of bioactive lipids, particularly ceramide, in the pathomechanism of autoimmune demyelination in MS. Specifically, we examined TNF- and IFN- effect, the two Th1 pro-inflammatory cytokines known to be accumulated in MS brain, upon a human oligodendroglioma (HOG) cell line. Our results suggested an exosome-mediated new mechanism of synergistic cytotoxicity of TNF- and IFN-. Ceramide-laden exosomes, when released from stressed or cytokine-targeted oligodendrocytes in vivo, may “broadcast” the cell death signal and promote the immune response that occurs under demyelinating conditions in the CNS. For this reason exosomes offer new molecular insights into MS pathology and perhaps could be used in the future as bioactive markers for the disease activity. On the other hand, it is well known that ceramide play a central role in sphingolipids metabolism which intricate scenario with numerous potential therapeutic targets, e.g. “engineered” exosomes can be used as an efficient vehicles for delivery of therapeutic agents across the blood-brain barrier.
A complex and heterogeneous picture of MS immunopathology may suggest the presence of various immunoregulatory abnormalities in this disease. These may result from disturbed functional interactions of many cellular components of the immune system, especially regulatory T cells. Natural killer T (NKT) cells may perform major regulatory functions in immunity, however their function in MS is not yet fully understood. In our studies, we identified glycosphingolipid (GSL)-reactive CD1-restricted lymphocytes especially those of the NKT and NKR+ phenotype and with T cell regulatory functions. GSL-driven anergy of circulating lymphocytes in MS suggests that the altered immune response in MS is via robust invariant NKT (iNKT) activation with potent cellular and cytokine activities. Diverse GSLs including the endogenous myelin acetylated-galactosylceramides (FMCs) can drive activation critical to controlling CNS inflammation and fostering myelin repair. Rendering iNKT-cells hyporesponsiveness to an endogenous GSL is a novel insight into diseases manifesting aberrant iNKT-cell activation. Furthermore, the state of anergy following stimulation with the auto-antigen FMC-7 may have significant clinical implications, according to the theory of antigen-specific therapy of autoimmune diseases.
An equally important factor in the pathology of MS, apart from (sub)acute demyelination, is progressive axonal and neuronal damage, resulting in accumulating neurological deficit and disability. Earlier reports indicate that calpain has been implicated in MS autoimmune mechanism, including demyelination, axonal damage, loss of neurons and oligodendrocytes and modulation of proteins involved in apoptotic pathways. We hypothesized that this Ca2+ dependent cysteine protease plays a key regulatory role in immune activation of MS pathology and its deactivation (inhibition) causes remission with control of autoimmune inflammation and neurodegeneration. Our studies yielded new findings regarding the mechanism of progressive MS that have implications for potential treatment. Based on two primary culture models  rat and human  we identified calpain as a key neuron injury signal driving the toxic component of reactive microgliosis. Specifically, we determined that calpain, released upon neuron damage, activates microglia to produce reactive oxygen species and nitric oxide that are selectively toxic to neurons. Our findings indicate that damaged neurons themselves are culpable in propagating further neurotoxicity with pro-inflammatory signals to microglia. These studies provide much needed insight into the nature of progressive phase of MS, with emerging putative preventive and therapeutic options. These novel findings (e.g., targeting calpain inhibition) may provide valuable insight into the mechanisms by which Th1 cells elicit neurodegeneration and appear promising in the treatment of progressive types of MS but also other neurodegenerative disorders.
Biography:
Dr. Maria Podbielska had done her Habilitation from Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland in 2019,Ph.D from Institute of Immunology & Experimental Therapy Polish Academy of Sciences, Wroclaw, Poland in 2003,Master of Science & Engineer: Wroclaw University of Technology, Department of Chemistry, Wroclaw, Poland in 1997 and Professional Experience is from Ludwik Hirszfled Institute of
Immunology & Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland and Postdocs are 2012 and 2014-2016 Medical University of South Carolina, Charleston, SC, USA ,2010-2011 Heinrich Heine University, Düsseldorf, Germany,2004-2010 Georgia Regents University, Augusta, GA, USA.
Honors and Awards:
2016 Certificate of the Polish-American Fulbright Commission received at the Ministry of Science and Higher Education in recognition of merits to promote Polish science and culture and to strengthen friendships between the peoples of the Republic of Poland and the United States of America through participation in the program of Fulbright Senior Award 2015-2016.
2015 Fulbright Senior Award nomination by the Polish-U.S. Fulbright Commission approved by J. William Fulbright Foreign Scholarship Board, Washington, DC, USA.
2014 Fellowship award approved by the Kosciuszko Foundation, New York, NY, USA.
2011 Du Pré Grant award approved by the Multiple Sclerosis International Federation, London, United Kingdom.
2007 Wroclaw Medical University Rector’s award for scientific publication, conducted in collaboration between Medical University and IIET, published in 2006 in the journal of the highest IF value (Galactosylation of IgG from rheumatoid arthritis [RA] patients-changes during therapy; Glycoconj. J. 23, 463-471, 2006).
2003 Award for Ph.D. dissertation, Institute of Immunology & Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Professional Memberships:
since 2016 Member of the Fulbright Scholar Alumni Program administered by the Council for International Exchange of Scholars, a division of the Institute of International Education, Washington, DC, USA
since 2015 Member of the Kosciuszko Foundation Research Alumni Program, Warsaw, Poland
since 2012 Member of the Multiple Sclerosis International Federation Research Alumni Program, London, United Kingdom
since 2008 Member, The International Society of Neuroimmunology
Selected Publications:
M. Podbielska, J. O’Keeffe, E. L. Hogan Autoimmunity in multiple sclerosis: role of sphingolipids, invariant NKT cells and other immune elements in control of inflammation and neurodegeneration J. Neurol. Sci. 385, 198-214, 2018.
N. M. Trager, J. T. Butler, J. Harmon, J. Mount, M. Podbielska, A. Haque, N.L. Banik and C.C. Beeson. A Novel Aza-MBP Altered Peptide Ligand for the Treatment of Experimental Autoimmune Encephalomyelitis. Mol. Neurobiol. 55(1), 267-275, 2018.
M. Podbielska, Z.M. Szulc, E. Kurowska, E.L. Hogan, J. Bielawski, A. Bielawska, N.R. Bhat. Cytokine-induced release of ceramide-enriched exosomes as a mediator of cell death signaling in an oligodendroglial cell line. J. Lipid Res. 57(11), 2028-2039, 2016.
M. Podbielska, A. Das, A. W. Smith, A. Chauhan, S. K. Ray, J. Inoue, M. Azuma, K. Nozaki, E.L. Hogan and N.L. Banik. Neuron-Microglia Interaction Induced Bi- directional Cytotoxicity Associated with Calpain Activation. J. Neurochem. 139(3), 440-455, 2016.
J. O’Keeffe, M. Podbielska, E.L. Hogan. Invariant natural killer cells and their ligands: focus on multiple sclerosis. Immunology 145, 468-475, 2015.
M. Podbielska, N.L. Banik, E. Kurowska, E.L. Hogan. Myelin Recovery in Multiple Sclerosis: The Challenge of Remyelination. Brain Sci. 3, 1282-1324, 2013.
E.L. Hogan, M. Podbielska, J. O’Keeffe. Implications of lymphocyte anergy to glycolipids in multiple sclerosis (MS): iNKT cells may mediate the MS infectious trigger. J. Clin. Cell. Immunol. 4, 144, 2013.
C. Gately, M. Podbielska, T. Counihan, M. Hennessy, T. Leahy, A.P. Moran, E. L. Hogan, J. O’Keeffe. Invariant natural killer T-cell anergy of circulating lymphocytes to myelin polyacetylated-β-galactosyl-ceramides in multiple sclerosis. J. Neuroimmunol. 259 (1-2), 1-7, 2013.
M. Podbielska, H. Krotkiewski and E.L. Hogan. Signaling and regulatory functions of bioactive sphingolipids as therapeutic targets in multiple sclerosis. Neurochem. Res. 37, 1154-1169, 2012.
M. Podbielska, S.B. Levery and E.L. Hogan. The structural and functional role of myelin fast-migrating cerebrosides: pathological importance in multiple sclerosis. Clin. Lipidol. 6(2), 159-179, 2011.
M. Podbielska, S. Dasgupta, S.B. Levery, W.W. Tourtellotte, H. Annuk, A.P. Moran, E.L. Hogan. Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid. J. Lipid Res. 51(6), 1394-1406, 2010.
M. Podbielska and E.L. Hogan. Molecular and immunogenic features of myelin lipids: incitants or modulators of multiple sclerosis? Mult. Scler. 15(9), 1011-1029, 2009.

Abstract:
The current study aims to analyze the length polymorphisms in sequence-tagged-site (STS) sY1291 of the Y chromosome in Vietnamese men of infertile couples. All 322 DNA samples were amplified with the sY1291 primer by the quantitative fluorescent polymerase chain reaction (QF-PCR) assay. DNA sequencing technique was employed to evaluate the accuracy of QF-PCR results. The study showed 273 out of 322 DNA samples had the presence of STS sY1291, accounted for 84.78%. The QF-PCR results showed that there were various lengths in STS sY1291: 507 bp, 512 bp, 523 bp and 527 bp. The most prevalent length in STS sY1291 was 507 bp (87.5%), the others were 512 bp (4.8%), 523 bp (4.8%) and 527 bp (2.9%). We found that the observed length polymorphisms derived from differences in the number of mononucleotide Thymine (T) repeats in its structure. It stretched from 22 T to 39 T. DNA sequencing results identified that the number of mononucleotide T repeats causes these polymorphisms. However, the pair-wise alignment between the obtained and reference sequence was 77%. It can be seen that the length polymorphisms in STS sY1291 observed in QF-PCR results was accurate but it is still difficult to sequence fragments with mononucleotide repeats.
Biography:
Dr. Cao Thi Tai Nguyen, was born in Quy Nhon, Vietnam. She received the B.A. degree in Biology from Quy Nhon University, in 2004, and the M.Sc. and Ph.D. degrees in Biotechnology from Can Tho University, Vietnam, in 2010 and 2019, respectively. She joined Tai Furniture Company, Vietnam, as a secretary and helped ELICs volunteer teachers from 2005 to 2006 at Quy Nhon University. Since March 2006, she has been a lecturer at Department of Biology – Genetics, Can Tho University of Medicine and Pharmacy, Vietnam. My current research interests include molecular biology, cell biology and genetics.

Abstract:
Gram-negative obligate anaerobic bacteria of the human GI-tract-microbiome and their immunogenic secretory products have significant potential to serve as a dynamic, life-long source of extremely potent pro-inflammatory enterotoxigenic compounds highly toxic to the central nervous system (CNS). These microbes and their secreted products: (i) are capable of generating a broad-spectrum of highly neurotoxic, pro-inflammatory and potentially pathogenic molecules; and (ii) these include a highly immunogenic class of amphipathic surface glycolipids known as lipopolysaccharide (LPS). Bacteroides fragilis (B. fragilis), a commensal, Gram negative, non-motile, non-spore forming obligatory anaerobic bacillus, and one of the most abundant bacteria found in the human GI tract, produces a particularly pro-inflammatory and neurotoxic LPS (Bf-LPS). Bf-LPS: (i) is secreted from the B. fragilis outer membrane into the external-medium; (ii) can damage biophysiological barriers via cleavage of zonula adherens cell-cell adhesion proteins, thereby disrupting both the GI-tract barrier and the blood-brain barrier (BBB); (iii) is able to transit GI-tract barriers into the systemic circulation and cross the BBB into the human CNS; and (iv) accumulates within CNS neurons in neurodegenerative disorders such as Alzheimer’s disease (AD). This presentation will provide evidence that the incubation of B. fragilis with aluminum sulfate [Al₂(SO₄)₃] is a potent inducer of Bf-LPS. The results suggest for the first time that the pro-inflammatory properties of aluminum may not only be propagated by aluminum itself, but by a stimulation in the production of microbiome-derived Bf-LPS and other pro-inflammatory pathogenic microbial products normally secreted from human GI-tract-resident microorganisms.

Abstract:
Obtaining sufficient donor islet β-like cells is the key to islet transplantation for type 1 diabetes mellitus. Bone marrow mesenchymal stem cells (BMMSCs) are expected to be ideal sources to obtaining islet β-like cells, however the low differentiation rate is an urgent bottleneck that need to be solved. Our group demonstrate that extracellular vesicles (Evs) derived from insulinoma can differentiate BMMSCs into islet β-like cells, and exosomes (Exos), a core component of Evs, had higher differentiation rate than Evs. In addition, we show that CD97 overexpressed Exos had higher differentiation rate than that of CD97 knockdown Exos. Furthermore, we clarify that CD97 promotes differentiation of mesenchymal stem cells into islet β-like cells through MAPK/Smad/Ngn3 pathway. Taken together, we demonstrate that insulinoma Evs, especially the Exos, were able to differentiate BMMSCs into islet β-like cells, and that CD97 plays a crucial role in the differentiation process.
Biography:
Dr. Chao Li (M.D. Ph.D.) is currently fellow of Department of Surgery,Second Affiliated Hospital of Zhejiang University, School of Medicine. In 2011, he finished his bachelor training of clinical medicine at Tongji Medical College, Huazhong University of Science and Technology. From 2011 to 2016, he received his M.D./Ph.D. education in Zhejiang University, School of Medicine, and undertook a half year visiting scholar training in the Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. His research focuses on diabetes mellitus and malignant tumors of digestive system, specialized in the treatment of diabetes mellitus using extracellular vesicles derived from mesenchymal stem cells, as well as the metastatic mechanism of pancreatic cancer.

Abstract:
Wound healing consists of an organized cascade of biochemical and cellular events that involve tissue repairs and regeneration. Hibiscus sabdariffa (HS) content of polyphenols may participate by its antioxidant and anti-inflammatory properties necessary for wound healing. The purpose of this study is to assess the effect of HS loaded in ointment base applied topically to rats exposed to burning compared to standard Iruxol^® ointment. Methodology: to assess wound healing potency, burn injury model was employed. Rats were divided into four groups, Group I: Normal topically applied with ointment base (Control). Group II: Burned rats were left without any treatment. Group III: Burned rats applied with topical Iruxol^® ointment. Group IV: Burned rats topically applied with prepared HS extract ointment. The groups were treated with respective ointments three times through 24 hours. The wound tissues were collected to detect the oxidative stress and inflammatory effect in tissues as compared to control group. Histological analysis for tissue samples also were being endorsed the results by promoting collagen formation, re-epithelialization and angiogenesis. Results implicate that HS enhances the healing potential of the skin by stimulating the levels of biomarkers required for skin regeneration through its strong antioxidant in HS ointment applied group. In addition, HS suppressed the inflammatory effect induced by burning through its down regulation of TNF-α level. Moreover, it shows that HS topical treatment significantly reduces the hypertrophic scarring by its effect against TGF-β level. Altogether, these results suggest that HS is a valuable bioactive compound to use in wound healing and may be used with Iruxol^® as synergistic product to accelerate wound processing.

Biography:
Dr. Rania Khalil has her experiences in molecular biology in improving the health and protection from diseases. Her papers based on expression of genes which develop new pathways for improving healthcare. She has written these papers after several trials in research, teaching and publishing. The basis is founded on comparing gene expression before and after treatment either with a drug, complementary medicine and or food supplement. This approach has different ways of focusing that may be correlated to genetically or environmentally point of view.

Abstract:
Human activity is a serious cause of huge changes in the environment and a constant reason for the emergence of new stress factors. Thus, to survive and reproduce, organisms must constantly implement a program of adaptation to continuously changing conditions. Presented here research are focused on tracking slow changes occurring in Spodoptera exigua (Lepidoptera: Noctuidae), that were caused by multigenerational exposure to sub- lethal cadmium doses. The insects received food containing cadmium at concentrations of 5, 11, 22 and 44 µg per g of dry mass of a food. The level of DNA stability was monitored by the Comet assay in subsequent generations, up to 36th generation. In the first three generations, the level of DNA damage was high, especially in the groups receiving higher doses of cadmium in the diet. In the fourth generation, a significant reduction in the level of DNA damage was observed, which could indicate that the desired stability of the genome was achieved. Surprisingly, however, in subsequent generations alternating increase and decrease of DNA stability was observed. The observed cycles of changing DNA stability were lasting longer in insects consuming food with a lower Cd content. Thus, a transient reduction in genome stability can be perceived as an opportunity to increase the number of variants which then undergo the selection. This phenomenon occurs faster if the severity of the stress factor is high, but low enough to allow the population to survive.
Biography:
Prof. Maria Augustyniak is working in the Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, Poland. Major scientific interests her are: aging theory, stress theory and the theory of natural selection under anthropogenic pressure; ecotoxicology; assessment of DNA stability under the influence of various environmental stress factors, including nanoparticles. Results of her works are published in prestigious journals, including: Carbon, Journal of Hazardous Materials, Fish & Shellfish Immunology, Chemosphere, Environmental Research, Scientific Reports, Environmental Pollution and many others.

Abstract:
Autophagy is a natural process which in physiological conditions is aimed at the elimination of destroyed or malfunctioning cell parts, organelles or molecules. Also, autophagy gets induced under stressing conditions in response to, for example, infection, starvation or oxidative stress. Cadmium as the metal regarded as highly toxic induces numerous harmful effects and reactions, including DNA damage, molecule function inhibition and oxidative stress, may also induce autophagy either directly, by interaction with molecules or indirectly through generation of free radicals. However, Cd also is known as a factor, the exposure to which may, after several generations, contribute to the selection of animal strains of increased tolerance to this element. In the Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, there is an unique strain of the moth S. exigua, selected to Cd for 170 generations (18 years). The strain exhibits cellular and organismal reactions that after the period of selection, resemble the ones noted for the control strain. Also, we have strains that are intermediate referring to both Cd concentration and time of exposure. Therefore, the aim of this study was to check whether the autophagy markers differs in insects of various Cd exposure history, including also additional acute intoxication. To reach the aim, two complementary methods: ELISA (LC3 protein level) and flow cytometry were used. Autophagy induction appeared to be significant only in the highest intensity of acute exposure.

Biography:
Dr. Agnieszka Babczynska, PhD, DSc in her research work she concentrates on relations between humans, animals and environment. As an enthusiastic ecophysiologist, in her work she apply widely understood biomarkers, from molecular markers to life history parameters, if they are able to throw a new light on the tolerance, adaptation, plasticity or selection processes of animals in response to external, especially anthropogenic factors. As animal models, she
usually uses invertebrates, with spiders and insects as her favorites. Equally eagerly she spends her scientific time in the laboratory and in the field. She is also an academic teacher and, she often organizes and takes part in popularization of researches among children and adults.

Abstract:
It has been noticed since ancient times that colds may cause all kinds of diseases. However, its underlying mechanism has not been fully elucidated so far. Located at the back of the nasal cavities, the epipharynx is a unique tissue that is vulnerable to the effects of upper respiratory tract infections and air pollution. The epipharynx is an immunologically activated site even under normal conditions, and enhanced activation of innate immunity is likely to occur in response to airborne infection. In addition, the epipharynx has abundant distribution of vagal nerve fibers. Chronic epipharyngitis is not a widely understood condition. However, because of its close link with the nervous system and immune systems, it may play an important role as a trigger for the development of autoimmune diseases and neuroendocrine disorders, including chronic fatigue syndrome and other somatic symptoms. Thus, the epipharynx-brain interaction and epipharyngitis related immunity are worth consideration in managing patients with autonomic nervous disorder and patients with autoimmune disease. Given that chronic epipharyngitis and its brain interactions are not fully understood, it is important to focus future research on this condition.
Biography:
Dr. Osamu Hotta, Medical Doctor (Ph.D.-medicine), now he is a Director of Hotta Osamu Clinic, Clinical professor of Tohoku Medical and Pharmaceutical University, Councilor of Japanese Society of Nephrology, and Chairman for Japanese Focal Inflammation related Disease Research Group (JFIR). He is a nephrologist, got Medical Doctor’s degree (Ph.D) at Tohoku University in 1993.

Abstract:
The neonatal splice variant of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA1b) is expressed specifically in myotubes and developing skeletal muscle1. This pump has a functional difference from its adult isoform, SERCA1a. The SERCA1a is expressed in myofibres of fast twitch muscle and has more capacity to pump against high vesicular Ca2+ concentration than SERCA1b does2. The only structural variance – the octapeptide tail in SERCA1b instead of the C-terminal glycine of SERCA1a3 – does not seem to explain the functional difference because the C-terminal tail protrudes into the sarcoplasm, not the lumen of the sarcoplasmic reticulum where the concentration of Ca2+ is accumulated4. This paradox hints to a possible regulatory mechanism exerted by micro peptides recently found abundant in developing muscle5. A developmental effect of this possible regulation will be presented.

Abstract:
Knowledge of human leukocyte antigen (HLA) allele frequencies is essential for bone marrow and kidney donor searches. The Romanian Caucasian population is heterogeneous and information on HLA polymorphism has not been well studied. We characterized the HLA genetic profile and allele frequencies of regional populations in Romania. HLA-A, B and DRB1 alleles were examined in 8252 individuals, belonging to the four main regions of Romania. The most common alleles found in the Romanian population are: HLA-A*01, A*02, A*03, A*11, A*24; HLA-B*18, B*35, B*44, B*51 and HLA-DRB1*01, DRB1*03, DRB1*07, DRB1*11, DRB1*13, DRB1*15, DRB1*16. More than half of the alleles are non-homogeneously spread in Romania.These results provide a starting point for future analyses of genetic heterogeneity in Romania.

Biography
Dr. Ileana Constantinescu has started her medical activity as a PhD fellow at the University Hospital of Wales, Cardiff, UK, working on growth factors involved in the pathogenesis of pituitary tumours. Her interest centres arround transplantation immunology, cancer immunology and virology. She has concentrated her efforts on three challenging topics: immunogenetics, new biomarkers, new genes involved in early cancer diagnosis, prognosis, immune system genetics in various diseases. At present she is an Editor-in-chief at Immunogenetics: Open Access Journal and professor of immunology at Carol Davila Medical and Pharmacy University, Bucharest, Romania.

Abstract:
Breast cancer is the most common malignant tumor in females. It represents a complex heterogeneous group of tumors that display significant diversity with respect to histopathological features and therapeutic responses. Many researchers have focused on biomarkers, which will facilitate detection of breast cancer in its early stages, and microRNAs have shown immense potential for this purpose. microRNAs are a family of highly conserved noncoding single˗stranded RNA molecules of 21-25 nucleotides. microRNAs have been shown to have important roles in oncogenesis, invasion, and metastasis via epigenetic post-transcriptional gene regulation. Recent evidence indicates that the expression of miR-181a is altered in breast tumour tissues and in the serum of breast cancer patients. Some studies have demonstrated the involvement of miR-181a in the control of gene expression in breast cancer. The main thrust of this presentation is to explain the potency of miR-181a as a prognostic and/or diagnostic biomarker and to discuss the targeting therapeutics, as well as the associated challenges.
Biography:
Dr. Pierre Hardy, MD, PhD is a clinical scientist, Professor of Pediatrics, Pharmacology and Physiology at the University of Montreal who has extensive experience in translational medicine regarding solid tumors, cancer biology, gene therapy and biotechnologies (application of nanomedicines in cancer therapy). He has published over 150 papers in peer-reviewed journals. Some of his recent publications include Journal of controlled release 298 (2019): 177-185; Experimental Cell Research 386 (2020): 111737.

Abstract
Locally advanced adeno- and squamous cell carcinoma of the esophagous (EAC, ESCC) and oral squamous cell carcinoma (OSCC) result in worse prognosis upon late diagnosis. We aim to identify tumor indicating ncRNAs in serum exosomes of tumor patients for earlier non-invasive diagnosis to contribute to a better outcome.
Differential gene and protein expression comparing tumor and normal tissues identified diagnostic, response predictive and prognostic tumor markers. Transfer to liquid biopsies now seems practicable by exosomes, components of the novel communication system of living cells. In addition to protein expressing genes, non-coding (nc-) RNAs like lnc-, circ-, and mi-RNA have been recognized as regulatory active key components with high impact for cancer development. Exosomal cargo provides an imense potential for creation of diagnostic marker signatures for earlier diagnosis. We profiled exosomal miRNAs, identified 80 exosomal miRNAs differentially concentrated between 12 OSCC tumor patients and 8 healthy blood donors. miRNome analysis was performed by TaqMan miRNA arrays. Six miRNA candidates have been selected for verification by 25 OSCC patients and 22 healthy blood donors. miR-409-3p has been identified as potential diagnostic candidate, p=0.001, fold change 0.203.
As an essiential step to detect tumor-indicative differences in exosomal cargo with better sensitivity 1. we need membrane proteins on the surface of the microvesicles, discriminating tumor cell secreted „oncosomes“ from exosomes originating from normal cells, 2. we aim to separate tumor cell derived „oncosomes“ from normal cells secreted exosomes, present in large abundance in serum of tumor patients.
By whole genome gene expression arrays we detected highly overexpressed membrane proteins as diagnostic signature which will be now examined in „oncosomal“ membranes for transfer to liquid biopsies.
Biography
Dr. Ute Warnecke-Eberz is a molecular- and microbiologist, obtained PhD at the Freie University of Berlin, Germany in 1990. She is a head of lab for antiinfectiva research at Bayer Pharmaceutical Research in Wuppertal, Germany, she develoved screening assays to find antibacterials inhibiting protein-DNA interaction. 1999 establishing the lab for molecular oncology of the General-, Visceral- and Cancer Surgery at University Hospital of Cologne, she started research on diagnostic, response predictive and prognostic tumor markers for esophageal, gastric, oral and lung cancer. Since 2017 Prof. at University Hospital of Cologne focussing on real-time quantification of gene expression, and transfer of tumor marker results to liquid biopsy format. Actually evaluating the diagnostic use
of serum exosomes and exosomal non-coding RNAs.

Abstract:
Mimosa, one of the most species-rich genera in the Leguminosae, exhibits a high diversity of trichomes. These structures are considered crucial to the taxonomy of the genus and are commonly used to delimit infrageneric groups. The last taxonomic revision by Rupert C. Barneby, published in 1991, provided an important reference in the understanding of trichomes in Mimosa, but some terminology still needs to be clarified and standardized. The present study describes the microstructure and anatomy of trichomes in Mimosa and suggests a terminological standardization for these structures in the genus. We examined the trichomes of 62 species and the terms used to classify them were compared with previous taxonomic studies in the genus. We recognize 15 types of trichomes primarily based on the number, arrangement, and secretory activity of cells (uni- versus multicellular, uni- versus multiseriate, simple versus branched, glandular versus non-glandular). We conclude that the type of trichomes, rather than the type of indumentum, should be used for comparative analyses.
Biography:
Prof. Lucas Sa Barreto Jordao is a Biologist, began his academic studies at the Rio de Janeiro Botanical Garden (JBRJ) during its graduation studying taxonomy of the genus Mimosa (Leguminosae). Obtained a master’s degree in Botany at the National Museum of Brazil in 2013 with a dissertation on floristic and taxonomic studies of Mimosa in the state of Rio de Janeiro, Brazil, and a doctorate in Botany at the JBRJ in 2019 with a thesis on phylogenetic studies based on molecular data and a taxonomic revision of four series of the genus. In 2016, he held an exchange where he worked at the New York Botanical Garden on the Reflora Project in which he digitized specimens from Brazilian flora stored at the NY herbarium, while developing part of his doctoral research. In 2019,he completed a post-doctorate at JBRJ exploring the use of many phylogenetic and biogeographic tools. He worked as a biology teacher in elementary and high school for six years. He also worked as a consultant in floristic surveys, forest inventories and botanical identification and, currently, he is a professor of Botany, Forensic Botany and Brazilian Environmental Law in a preparatory course for application processes of government jobs, and in a specialization course (“Post-graduation lato sensu”). Since March 2020, he has worked at National Center for Flora Conservation/JBRJ assessing endangered species. His interest in trichomes arose from the need to understand the morphological diversity of Mimosa.

Abstract:
Indigofera cordifolia Heyne ex Roth. so far is reported only in the Arabian Peninsula from Oman. A recent field expedition in the Farasan Archipelago, Saudi Arabia, Red Sea, resulted in documentation of this species in Dumsuk Island. Morphological examination and molecular identification based on the nuclear ribosomal DNA internal transcribed spacer region of this plant species was investigated in this study. The result show that the internal transcribed spacer had high species-level discrimination efficiency for the identification of Indigofera cordifolia that may provide help in authentic identification and management process of this rare and nationally endangered species.

Abstract:
This case report describes a fetus with compound heterozygosity for Hb G-Hsi-Tsou and beta thalassemia, diagnosed in a healthy pregnancy. To the best of our knowledge, this is the first documented case of compound heterozygosity and the woman is the second known case of heterozygosity for Hb G-Hsi-Tsou. A 34-year-old woman during her first pregnancy underwent routine early pregnancy screening and several tests were performed. All tests were normal, with the exception of hemoglobin electrophoresis, which revealed heterozygosity for Hb G-Hsi-Tsou. Hemoglobin G-Hsi-Tsou constitutes a hemoglobin variant with a structural abnormality of the beta chain, first described in 1972, but since then no other cases have been reported. After finding out that her husband was heterozygous for beta thalassemia, chorionic villus sampling revealed the embryo’s heterozygosity for both Hb G-Hsi-Tsou and beta thalassemia. Due to lack of scientific data, the couple decided to end the pregnancy. It was not possible to determine whether the fetus would present serious deficiencies in hematopoiesis, as Hb G-Hsi-Tsou is a variant which is not yet fully understood. What made this case even more complex was the simultaneous presence of the beta thalassemia allele.
Biography:
Maria Androulaki graduated from the Department of Medicine, University of Patras, Greece, in 2019. She is currently in her first year of Obstetrics and Gynecology residency at General Hospital of Messinia, Kalamata, Greece. During her medical studies, she completed clinical internships at the Department of General Surgery at Zagazig University Hospital in Egypt and at the Department of General Surgery, Antoine-Béclère Hospital in Paris, France. Her main domain of interest is maternal-fetal medicine.

Abstract:
Hepatitis C virus infection is endemic in Egypt with the highest prevalence rate in the world. Without treatment, most acute infections lead to chronic, followed by cirrhosis and hepatocellular carcinoma. Sofosbuvir acts like a nucleos(t)ide analogue that specifically inhibits hepatitis C virus replication. Our study aimed to explore the molecular mechanisms and the possible side effects of the therapeutic dose of sofosbuvir on mitochondrial biogenesis and functions of liver, muscle and ovary tissues of young normal female rats and explore the possible prenatal effect of Sofosbuvir on the embryos of the exposed mother. The study was conducted on female albino rats 2 months old that was classified into 2 groups. Group I (Control group): 20 healthy female rats and Group II (exposed group): 20 female rats that was supplemented with 4 mg/kg of sofosbuvir drug for 3 months. At the end of the treatment period, 10 normal and 10 exposed female rats will be sacrificed and dissected out to obtain blood, ovary, liver and muscles. Pregnancy will be induced in 10 control females and 10 exposed females by mating with healthy male rats overnight. At gestational day 17 (GD 17) pregnant control females and pregnant exposed females will be sacrificed by cervical dislocation. The embryos with their membranes and placentas will be quickly dissected out of the uterine horns. Each embryo will be dissected to obtain the fetal liver, and muscles. The reported toxicity was mediated through suppression of Peroxisome proliferator-activated receptor gamma coactivator- 1alpha (PGC-1α), mitochondria transcription factor A that impair mitochondrial biogenesis that manifested a decline in mitochondrial DNA copy number. Also, sofosbuvir suppresses the expression of DNA polymerase γ and declines the mitochondrial NADH dehydrogenase subunit-5 content that impair the mitochondrial functions. According to our results, the ovarian tissue is the most affected organ followed by the liver and placenta while muscle tissue appears to resist sofosbuvir-induced mitochondrial toxicity. In conclusion, the effects of sofosbuvir on the ovarian mitochondrial biogenesis and functions was found to not just affect the exposed females but unfortunately may have long-lasting consequences by impairing the embryonic development and transfer these mitochondrial abnormalities to next generations.
Biography:
Dr. Rana Hassan Mahmoud Hassan Khafaga, born on 4\11\1989.She completed her graduation, Class of 2012, Alexandria University, Faculty of science, Biochemistry Department,currently she is Assistant lecturer at Biochemistry department at Medical Research Institute (MRI), Alexandria University, Egypt and she is a student in Ph.D degree in MRI Alexandria University since February 2018 and Working on a Project accepted by STDF organization titled by: Short-term and long-term trans-generational side effects of Sofosbuvir: Experimental study on female rats, 2019. She has attended many international conferences and has many awards.

Abstract:
Cadmium toxicity to animals depends on their tolerance mechanisms. The harmful action of this metal takes different forms, starting from blocking of intracellular signalling receptors, through induction of oxidative stress, to genotoxic effects.
Cadmium tolerance developed in an unique strain of the moth Spodoptera exigua selected for over 170 generations in Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice can be based on many mechanisms at both: cellular and molecular level. It cannot be excluded that multigenerational exposure to Cd may lead to the selection of insects that have a wider tolerance to oxidative stress.
Reactive Oxygen Species (ROS) are molecules present in cells undergoing oxidative stress. Oxidative stress level was measured in the hemolymph and midgut cells of the 5th larval stage after 1–6, 12, 18 and 24 generations of differential cadmium exposure in comparison with insects after multigenerational exposure (170 generations) and control strain. The assay used in present studies was to detect the relative percentage of cells that are ROS negative and positive. Thanks that, two populations of cells can be distinguished: live (ROS-) cells and cells exhibiting ROS (ROS+).
The pattern of the cell populations percentage/ratio in both hemolymph and midgut cells depend on the concentration of this metal in the food and the time of Cd exposure.
Biography:
Dr. Monika Tarnawska is working in the Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, Poland. Major scientific interests of her are: ecotoxicology of terrestrial invertebrates, especially crop pests, activity and immunodetection of general stress proteins. Results of her works are published in prestigious journals, including: Fish & Shellfish Immunology, Chemosphere, Ecotoxicology, Ecotoxicology and Environmental Safety, International Journal of Pest Management and others.

Abstract:
Vision is essential for vertebrates including humans. Sustained vision is accomplished by the retinoid metabolism, ‘visual cycle’, where all-trans retinol (atROL) is released from photoreceptors upon light absorption and is incorporated into the adjacent retinal pigment epithelium (RPE). In the process, a receptor of atROL is assumed; however, the entity has been missing for a decade. In my talk, I would like to give a presentation about our recent finding showing that low-density lipoprotein (LDL)-related receptor-5 (Lrp5) protein is a strong candidate for the receptor of atROL in the visual cycle (Takita and Seko, iScience 2020; 23(12): 101762). We generated and analyzed the digenic eyes shut homolog (eys)+/-; lrp5+/- zebrafish, the same form of gene defects emerged from a human case report of a candidate retinitis pigmentosa, the most common genetic disorder in inherited retinal dystrophies. The mutant photoreceptor cell layer (PRCL) was mildly thinner than the wild-type PRCL and global gene expression analysis revealed that the hallmark was remarkable decrease in the expression level of the retinol binding protein 1a (rbp1a) gene. The genetic interaction study using rbp1a-/- and lrp5-/- zebrafish eyes clarified that rbp1a gene played a role downstream of lrp5 gene. Immunohistochemical analysis revealed that Lrp5 protein was colocalized with Rbp1a protein at the microvilli of RPE cells in the outer retina. Furthermore, in vitro binding assay using full-length Rbp1a protein and C-terminal intracellular region of Lrp5 protein revealed that they directly bound each other. Collectively, these results strongly suggest that Lrp5 protein is a potent candidate of the receptor of atROL in the visual cycle. This work also indicates that combination of detection and comprehensive analysis of polygenic inheritance could be a powerful tool to dissect molecular networks such as protein-protein interactions and protein complexes not only in vision but also in other fields of biology and medicine.
Biography:
Dr.Shimpei Takita has primarily worked on vision having interests in identification of key genes important for specialised sensory neurons and their supporting cells (i) to be specialised for detecting external stimuli and (ii) to be finely-organised and well-maintained.

Abstract:
Myopericarditis is a rare consequence of COVID-19 infection. Although extremely rare, COVID-19 can present without pulmonary involvement, and there have been reports of isolated cardiac involvement in one prior case
We report a case of a young African American man presenting with myopericarditis following a recently recovered COVID-19 infection. Complicated by ICU admission requiring vasopressors; with eventual resolution following initiation of aspirin and colchicine for myopericarditis.
Life threatening myopericarditis can occur following resolution of COVID-19 disease. The degree of cardiac involvement correlates poorly to the severity of pulmonary involvement.
Biography:
Dr. Steven Mirabella is an industrious 3rd year Internal Medicine Resident completing training at a busy New York hospital in Long Island. He has extensive clinical experience managing COVID-19 infection. He has given multiple poster presentations at the American College of Physicians (ACP) Scientific meetings; as well as the 15th Annual Medical Society of the State of New York (MSSNY) Resident/ Fellow Poster Symposium in Tarrytown New York. Most recently he was awarded first place along with his colleagues at the 2021 American College of Osteopathic Internists (ACOI) Resident/Fellow Case Presentation Contest in Orlando, Florida, USA. He was enthralled to be able to share his recently published work and experience with such a wide audience.

Abstract:
Iodothyronines are potent regulators of white adipose tissue functions and development. Endogenous 3,3’,5-triiodo-L-thyronine (T3) regulates lipolysis, lipogenesis, thermogenesis, and mitochondrial functions. However, excess of T3 induces heart rhythm abnormalities, muscle wasting, and reduced bone density, so that applying this hormone as a pharmacological compound has been discouraged in obesity and related diseases. 3,5-diiodo-L-thyronine (3,5-T2) seems to act through nuclear thyroid hormone receptors-independent pathways, with mitochondria as a likely cellular target. Specifically, 3,5-T2, when administered to rats receiving a high-fat diet (HFD), increases energy expenditure and prevents HFD-induced adiposity, without inducing alterations of the hypothalamus-pituitary-thyroid axis, and of skeletal muscle and heart mass. In HFD rats, by a combined approach, including large-scale expression profile and functional analyses, we demonstrated that 3,5-T2 has an anti adipogenic/lipogenic potential, in vivo modulating adipose tissue proteome, affecting proteins involved in lipid storage, oxidative stress, and lipogenesis-associated mitochondrial function. All this, combined with the previously described increased oxidative capacity of liver, expands on the notion of the prevention of fat mass-gain by 3,5-T2 and contributes to further explaining the action of this intriguing naturally occurring thyroid hormone metabolite.
Biography:
Dr.Elena Silvestri Born in Benevento, Italy. Associate professor of Physiology, University of Sannio, Benevento, Italy. Research themes: a) peripheral mediators of thyroid hormone action: diiodothyronines; b) mitochondria and cellular thermogenesis; c) thyroid hormones and uncoupling proteins; d) proteomics of metabolically active animal tissues under physio–pathological conditions (thyroid states, obesity, ageing, AD). Editorial activity Reviewer for several international journals. Co-Guest Editor for special issues of Nutrients and Frontiers in Endocrinology. Fellows – Since 2006 she is member of the Italian Physiology Society and since 2013 member of the European Thyroid Association (ETA). Awards – September 2021 – The ETA Max Pierre König Poster Award, in recognition of the best poster in basic thyroidology: Differential deranged liver pathways in genetically determined thyroid dysfunctions: intra- and extrahepatic factors, at the 43rd Annual Meeting of the Association 4th – 7th September 2021 -September 2008 – National Award for young researchers in Physiology (Società Italiana di Fisiologia) -July 2006 – The Italian Proteomic Association, Pisa, Italy. Beckam Coulter Aword in Proteomics (BeCap Beckman) 3,5,3′-Triiodo-L- Thyronine And Rat Liver Mitochondria Phenotype: A Proteomic Approach.

Abstract:
Endometrial regeneration is a dynamic process that is not well understood. The destruction of the endometrium with the formation of intrauterine adhesions is known as Asherman’s syndrome. The lesions range from minor to severe adhesions and their impact on pregnancy is well documented. Operative hysteroscopy is the mainstay of diagnosis and treatment of intrauterine adhesions. Nevertheless, the recurrence rates remain high. It was recorded that low-level laser therapy in low doses has a stimulatory effect on different tissues while the high dose produces a suppressive effect. Organoid is a three-dimensional assembly that displays architectures and functionalities similar to in vivo organs that are being developed from human or animal stem cells or organ-specific progenitors through a self-organization process. Our prospective was to study the effect of Low-Level Laser Therapy (LLLT) on mouse epithelial endometrial organoids regarding cell proliferation and endometrial regeneration as a new modality of treatment. An in vitro clinical trial to generate mouse epithelial organoid model and testing LLLT using He:Ne 632.8 nm device on organoids proliferation, function, and their response to ovarian hormones was performed. Trying endometrial regeneration by culturing organoids with decellularized uterine matrix (DUM) and studying the LLLT effect on the regeneration process. LLLT produced a proliferative effect on the epithelial mouse organoids confirmed by Ki67 and PCNA IHC. The organoids could regenerate the epithelial layer of the endometrium in vitro on DUM and LLLT could help in this process. In conclusion, organoids whether control or bio-stimulated proved a new modality to regenerate the endometrium.
Biography:
Mona Gebril is a Researcher of Obstetrics and Gynecology in Reproductive Health department, National Research Center of Egypt. She obtained her MBBCh from Cairo University School of Medicine, then got Master degree in Obstetrics and Gynecology and PhD in Laser application in Gynecology, Cairo University. She had her Ph.D. Joint Supervision Scholarship from Culture Affairs and Mission Sector, Ministry of Higher Education and Scientific Research in Egypt for three years in Tokyo University Graduate School of Medicine. Her interested in endometrial physiology, receptivity and regeneration. She Succeeded to generate endometrial epithelial organoids mice model for this purpose.

Abstract:
The most common symptoms of primary gastrointestinal (GI) lymphoma are non-specific, such as nausea, vomiting, diarrhea, weight loss, and abdominal pain. The rare acute symptoms include bowel obstruction, intussusception, and perforation. Primary small bowel lymphoma accounts for the smallest proportion of all GI malignancies. We report a case of intestinal lymphoma presenting with bloody stools and anemia. The patient initially underwent both duodenoscopy and colonoscopy with negative findings. Isotopic red blood cell (RBC) scan was then performed due to persistent bleeding along with computed tomography angiography (CTA) because of suspected bleeding in the left abdomen. Successful embolization over the arcade of the sigmoid and left colic arteries was performed. However, the bleeding did not stop, and ischemic colitis was diagnosed by repeat colonoscopy. A coloenteric fistula was finally discovered during emergent laparotomy. This is a rare condition that has not been previously described in Taiwan. Early diagnosis and timely management will decrease morbidity and mortality in the GI lymphoma population.
Biography:
Shih-Wei Chiang, M.D. is visiting staff of Colorectal surgery. He completed his coloproctology residency at the Taichung Veterans General Hospital, Taichung where he served as chief resident during his final year. He is board certified in coloproctology and colorectal surgery. His academic interests include colorectal surgery, colorectal cancer and laparoscopic surgery.

Abstract:
Leucine-rich repeats (LRRs) occur in tandem and the repeat unit lengths (RULs) in general range from 20 to 29 residues. Seven LRR classes have been recognized. A comprehensive sequence analysis of viral LRRs has been done. Most proteins are from nucleocytoplasmic large dsDNA viruses (NCLDVs). The RULs of several LRR types are one to five residues shorter than those of the known, corresponding LRR types. Surprisingly, the RUL of 19 residues which is the shortest among all LRRs are identified in some LRR types. Unique LRR motifs are also observed. The present findings provide a new perspective on the origin and evolution of LRRs.
Biography:
Dr. Norio Matsushima is Professor Emeritus of Sapporo Medical University. He received his Ph.D. in polymer physics at Hokkaido University in 1976. He joined Sapporo Medical University from 1983. In 1986-1988 he joined the University of Virginia, USA. He studied the structure and evolution of protein tandem repeats including leucine-rich repeats and also developed the HEFIT program for fitting helices. He has published over 100 papers in peer reviewed journals and a book. He is the editorial board member of “Protein and Peptide Letters”.

Abstract:
Small cell lung cancer (SCLC) remains a major challenge in public health because of its frequency, its lethality, and the paucity of convenient models for exploring its pathogenesis and potential therapeutic vulnerabilities. Despite recent research advances, fundamental features of SCLC, especially its initiation and progression, are not fully understood. One of the main obstacles is the development of a feasible and tractable system that allows molecular events to be evaluated for their functional changes towards the hallmarks of neoplasia during lung lineage differentiation.
To understand how and why certain constellations of genetic changes drive carcinogenesis in specialized human cell lineages, we are developing cell culture models based on directed differentiation of human embryonic stem cells (hESCs). In this report, we show for the first time that up to 10 percent of lung progenitor cells derived from hESCs can be induced to form pulmonary neuroendocrine cells (PNECs), the putative normal precursors to SCLCs, by inhibition of NOTCH signaling. In such cultures, reduction of the retinoblastoma (RB) protein, the product of a tumor suppression gene commonly mutated in SCLCs, significantly expanded the number of PNECs. But reduction of TP53 protein, the product of another tumor suppressor gene uniformly mutated in SCLCs, or expression of mutant KRAS or EGFR genes, each of which is commonly found in human lung adenocarcinomas, did not induce or expand PNECs, suggesting a lineage-specific sensitivity to loss of RB function. Subcutaneous injection of PNEC-containing cultures in which expression of both RB and TP53 was blocked produced tumors resembling early stage SCLC in immunodeficient mice. Single-cell RNA profiles of PNECs were heterogeneous; when RB levels are reduced, the profiles show similarities to RNA profiles from early stage SCLC. Taken together, these findings suggest that genetic manipulation of hESC-derived pulmonary cells will enable studies of the initiation, progression, and treatment of this recalcitrant cancer.
Biography:
Dr.Huanhuan Joyce Chen has received her Pharm.D. degree in Pharmaceutical Sciences at Zhejiang University in China, M.S. and Ph.D. degrees in Biomedical Engineering at Cornell University. She will be enrolled as an Assistant Professor in Pritzker School of molecular engineering and the Ben May department for cancer research at The University of Chicago in May 2020, and is currently a postdoctoral fellow with Dr. Harold Varmus at Weill Cornell Medicine. She received a number of awards including NIH Pathway to Independence Award (K99/R00), Arnold O. Beckman Postdoctoral Fellowship, National Cancer Institute Physical Sciences in Oncology Young Investigator award and National Science Foundation Graduate Research Fellowship. She has published more than 19 papers in reputed journals, including Nature Biotechnology, Nature Medicine, Nature Communication, Cell Stem Cell, Journal of Experimental Medicine, Journal of Clinical Investigation, Lab on Chip and eLife. Her research is focused on stem cell technology and tissue engineering for modeling and studying cell biology and genetic diseases.

Abstract:
Biological therapies such as immunotherapy and oncolytic virotherapy are physiological and well tolerated by cancer patients. The combination of cancer vaccines with oncolytic viruses is a powerful concept. Two types of autologous cancer vaccines will be described which are modified by infection with the avian Newcastle disease virus. They instruct the immune system about relevant cancer targets (tumor antigens, TAs) and contain signals for innate immunity activation. Viral molecular patterns such as S’-PPP RNA and hemagglutininneuraminidase (HN) protein initiate early inflammatory defense reactions which contribute to activation of antigen-presenting cells (APCs) and to costimulation of T cells. The concommitant stimulation of TA-specific CD4+ and CD8+ T cells occurs in T-APC clusters. These generate cancer-reactive cytotoxic T lymphocytes (CTLs) and T cell mediated long-term immunological memory. Results from pre-clinical and clinical studies will be presented.
Biography:
Dr. Volker Schirrmacher is a Scientific Director of Tumorimmunology at IOZK, Cologne, Germany. He finished his studies of biochemistry with a PhD in immunology. After 5 years post-doc time in Stockholm, Sweden and London, UK, he became Full Professor and Head of Division of Cellular Immunology at the German Cancer Research Center, Heidelberg, Germany. This position was hold for 32 years until official retirement in 2008. His scientific oevre covers more than 400 peer-reviewed publications and several books. He was awarded the Aronson Price, the Meyenburg Price and the German Cancer Award.

Abstract:
Patients with myopia are at increased risk for the development of glaucoma. The inability to correct for axial length on spectral domain OCT (SD-OCT) imaging translates into a lower signal strength and scan reliability in patients with high myopia. We evaluated the effectiveness of a contact lens to increase the signal strength, assess optic nerve dimensions and nerve fiber layer thickness using SD-OCT in patients with glaucoma or who are glaucoma suspects with high axial myopia.
Methods- A single-center, prospective, interventional study of patients with axial lengths over 25.5 mm with a diagnosis of glaucoma or glaucoma suspect. The optic nerve cube 200 x 200 scan using the Cirrus SD-OCT 400 was taken first without and then repeated after the placement of the contact lens. The primary outcome measure was the change in the average nerve fiber layer thickness before and after use of the contact lens. Secondary outcome measures included the change in cup volume, disc area, and rim area.
Results- Twelve patients were recruited (20 eyes) and the average axial length was 27.06 mm and the average signal strength interval increased by 1.73 (p= 0.001). With the use of a contact lens, the average nerve fiber layer thickness was significantly thicker. None of the changes in the secondary outcome measures were significant: rim area, cup volume, or disc area. Conclusions- Based on our data, the use of a contact lens statistically improved the signal strength and average nerve fiber layer thickness of the SD-OCT scan. The ability to accurately capture the perimeter of the optic disc can be limited in the setting of peripapillary atrophy, which was present in all but two subjects. Future studies with a larger number of subjects and a wider range of axial myopia to discern if contact lens correction has a greater effect on the highest axial lengths are needed.
Biography:
Dr. Meghan K. Berkenstock has become an emerging leader in the field of ocular immunology. She is an Assistant Professor of Ophthalmology at the Wilmer Eye Institute of the Johns Hopkins School of Medicine, her research focuses on quality improvement and identifying and treating ocular side effects of oncologic immunotherapy medications.

Abstract:
Monoclonal antibodies (MAbs) are rapidly growing class of therapeutic molecules in biopharmaceuticals. More than 80 therapeutic antibodies have been approved by the FDA in the last 30 years for different indications ranging from oncology to autoimmune diseases to respiratory diseases and the number is increasing year by year. Most of the current therapeutic antibodies are immunoglobulin G (IgG) with glycosylation constituting around 3% of the total mass of the molecule. Understanding the impact of glycosylation and close monitoring is critical for monoclonal antibodies and fusion proteins development as therapeutic molecule. Different forms of glycan including sialic acid (NANA/NGNA), galactose, mannose and fucose influence safety, efficacy and pharmacodynamics/pharmacokinetic property (PD/PK) of the therapeutic monoclonal antibodies and fusion proteins. This presentation will highlight the influence of different glycan variants on the drug’s behaviour in the body and draw attention to commonly employed analytical techniques to analyse therapeutic molecules and determine and quantify glycan composition, structure and glycosylation site in them.
Biography:
Dr Harleen Kaur has been in the pharmaceutical industry for almost 8 years and most recently led the analytics and drug product tech transfer projects for two biologics products while working at AstraZeneca, USA. Prior to this, she worked in R&D division of Fujitsu Asia Pte Ltd in Singapore where she worked on aptamer development and played an integral role in identifying and purifying aptamers against different protein targets in collaboration with National University of Singapore, Agency of Science Technology and Research Singapore, and Japanese diagnostic enterprise Sysmex. In her current role, she is leading a team of analytical scientists at Aurobindo Biologics and her responsibilities include the method development, method qualification and method transfer for different biosimilar products. she completed her PhD in chemical and biomolecular engineering department at National University of Singapore.

Abstract:
Induction of the Phase 2 enzymes is a major strategy in the chemoprotection against cancer. Inducers belong to nine different chemical classes. In this contribution we found that a measure of the tendency of thirty plant phenylpropenoids and synthetic analogues to release electrons correlates linearly with their potency in inducing the activity of NAD(P)H:quinone reductase (NQO1), a prototypic Phase 2 cancer protective enzyme.  The tendency to release electrons was determined by the energy of the highest occupied molecular orbital (EHOMO), calculated by simple quantum mechanical methods. The correlations observed establish a clear conclusion: the smaller the absolute Energy of the Highest Occupied Molecular Orbital (EHOMO) of an agent, the greater its inducer potency, (i.e., the lower its oxidation potential, the stronger its electron donor property and the greater its inducer potency). The finding of this redox ranking of the inducers demonstrates that it is possible to predictively control the genetic expression of an enzymatic defense against cancer by xenobiotics via one physical parameter, their EHOMO.

Abstract:
Polytene chromosomes are interphase chromosomes consist of homologous chromatids, which are amplified through consecutive cycles of endoreduplication and conjugate together. Polytene chromosomes are formed in the nuclei of cells that require intense synthesis of substances in highly specialized tissues.
Antipodal cells of embryo sac of wheat is an example of plant cells with polytene chromosomes. Antipodal complex is located in the ovule between the nucellus and endosperm. Antipodal cells form a complex consisting of three cell layers – basal, which contacts with the conductive tissues, middle and apical, which contacts with the endosperm. After double fertilization antipodal cells produce substances necessary for the emerging endosperm coenocyte. Antipodal cells belong to the tissues that perform trophic and barrier functions between the maternal organism and the tissues formed after fertilization. So they play key role in development of endosperm and moreover are crucial for formation of endosperm in cultivated cereals, which are food for all the humanity.
The aim of our work was to study the morphology of the nuclei and giant polytene chromosomes of antipodal cells. The work was performed on total specimens of embryo sacs isolated from fixed wheat ovules. We used methods of light microscopy and transmission electron microscopy.
We measured DNA content in the nuclei of the antipodal cells and found that nuclear DNA content varies in the cells of the complex. The basal layer cells contain less DNA than apical layer cells. During the differentiation DNA content of nuclei increases.
Structure of antipodal polytene chromosome differ from structure of animal polytene chromosomes. Animal polytene chromosomes have disks and interdisks as a result of conjugation of chromatids along the entire length of the polytene chromosome. In regions of polytene chromosomes with the intensive synthesis of RNA, decondensation of chromatin occurs and puffs are formed. On the contrary antipodal cells are characterized by giant chromosomes in the form of bundles of threads and conjugation is found only in centromere regions. At the initial stages of the differentiation nuclei of antipodals have approximately the same size and nonsegregated polytene chromosomes. Then the nuclei of middle and apical layer cells increase in size, they have isolated individual chromosomes.
To conclude, the antipodal cells of the embryo sac in cereals are a unique object for solving the fundamental problems of cell biology and a convenient model for studying the structure of the nuclei and the stages of reforming polytene chromosomes during ontogenesis.

Biography:
Tatiana Doronina is a 2nd year PhD student in Lomonosov Moscow State University, Biology Faculty in Russia at the Department of Cell Biology and Histology. The field of interest is plant cell biology, polytene chromosomes and programmed cell death.
Publications:
•Doronina, T. V., Chaban, I. A., & Lazareva, E. M. 2019) Structural and Functional Features of the Wheat Embryo Sac’s Antipodal Cells during Differentiation. Russian Journal of Developmental Biology, 50(4), 194-208.
•Doronina, T. V., Chaban, I. A., & Lazareva, E. M. 2019. Structural reorganization of nuclei of wheat antipodal cells during programmed cell death. Biopolymers & Cell, 35(3), 206.

Abstract
Background: Type 2 myocardial infarction (MIT2) is characterized by higher mortality rates compared to conventional type 1 infarction according to the European Society of Cardiology (ESC) in 2018. The purpose of this case is to identify appropriate therapeutic measures. A case of an Amyand’s Hernia that produced an MIT2 is described in this work.
Case Report: A 77-year-old male was admitted to our emergency department for acute abdominal pain in the right lower quadrant associated with the presence of an ipsilateral inguinal hernia with signs of peritoneal irritation, while complaining of chest pain. A positive troponin indicated the presence of myocardial infarction. A laparotomy was performed with the finding of an incarcerated right inguinoscrotal hernia that contained the gangrenous and perforated cecal appendix (Amyand hernia type 3). The treatment consisted of surgical correction of the hernia, an appendectomy, antibiotics and support in the intensive care unit with a positive outcome. The diagnosis of Amyand hernia type 3 was established intraoperatively, and by imaging, confirming the presence of an MIT2 according to the criteria of the fourth definition of ECS infarction.
Conclusion: In the surgical environment it is strange to find patients who present with acute abdominal pain and a myocardial infarction at the same time. It is necessary for the consultant to recognize these two entities to make a correct diagnosis and provide timely treatment to reduce any possibility of patient mortality
Biography:
Dr. Silvia Barbosa is a physician at the Fundacion Cardioinfaltil in Bogota Colombia, She is a part of the research group of general surgery and emergency with the aim of improving and promoting the scientific development of her country and society. They are a leading hospital in Latin America and it is through science that they can get more answers every day by sharing knowledge.Her interest is to share the complexity of the human being, how two or more entities can appear in a single patient at the same time that they are different from each other but they are interconnected and our challenge is to define how to solve them all.

Abstract:
Digital pathology is rapidly evolving, transforming qualitative paradigms to quantitative ones, increasing histological examination objectivity. With a compound annual growth rate of the market over 10%, scanning devices with a higher slide capacity, speed and resolution become available. Not of less importance is software, varying from free basic viewers ending with advanced machine learning algorithms promising (semi) automatic diagnosis. To a significant extent, the advantages of computer-assisted image analysis may first be experienced via open-source solutions. The session provides an overview of existing free WSI-oriented solutions and examples of possible applications in teaching, scientific research, and pathologists’ daily practice.
Biography:
Dr. Georgi Dzaparidze, the founder of Estonian Digital Pathology Association. Co-developer of the first digital-pathology department in Estonia. Co-author of digital pathology solutions for medical and medical technician students in Estonia.

Abstract:
Globally, efforts to advance malaria control and prevention have focused on two main areas of research: (1) Finding vaccine candidates to immunize populations and prevent posterior infections, (2) Finding novel and unknown molecules and fields where remain interesting questions unsolved. The intracellular malaria parasite Plasmodium falciparum organization, particular organelles as endoplasmic reticulum and domains of the infected erythrocytes affected by changes and modifications to evading the immune response, are important basic studies. P. falciparum export virulent proteins and built a complex cell modified to transport proteins traversing three concentric membranes or cellular compartments as; plasmatic membrane of the parasite, parasitophorous vacuolar membrane, and plasmatic membrane of infected erythrocyte getting alterations for own benefit and survive. Released merozoites ending the intraerythrocytic cycle after 48 hours of the invaded cell cause symptoms of disease, physiopathology and are highly immunogenic. Our group prepared monoclonal antibodies to study the event that occurs when merozoites egress from their host, this immunogen inoculated to generate the antibodies recognizing proteins localized in the Protein export compartment (PEC). PEC is a domain of the endoplasmic reticulum that could be associated with egress merozoites. However, before studying this event, it is necessary to know the identity of proteins localized in PEC. One of the proteins localized is named Pf68kDa, which is the first resident protein of PEC, identified and is recognized by a monoclonal antibody, mAb7.
We show identification of the 68 kDa antigen of P. falciparum. Recently works identified Pf68 kDa as two proteins by different methodological strategies, and the same mAb7: the first protein identified as a homolog of HSP70/BiP/GRP78, named PfHSP70-2 by affinity chromatography and mass spectrometry, and the second protein identified, Plasmodium WD40 repeat-containing protein-1 (PlasWD40-1) identified from a cDNA expression library screened with Mab7. From the plaques analyzed, two positive clones ultimately were identified. Thus, Mab7 not only recognizes PfHSP70-2 but also recognizes a protein expressed by the cloned DNA fragment (MK618679). Now, We know more about the nature of PEC, and not much about PlasWD40 and Pf68kDa is not precisely known. It is unknown if a common epitope between PfHSP70-2 and PlasWD40-1 is a coincidence or both proteins are interacting or regulating functions to directing activities in the endoplasmic reticulum to exporting proteins to the plasmatic membrane of P. falciparum-infected erythrocytes. The target from these two proteins and common epitope or each one separately, could to proposing new possible therapeutic strategies against malaria.
Biography:
Dr. Gladys Thalia Cortes obtained her Ph.D. in Biotechnology from Science Faculty at Universidad Nacional de Colombia (2020), Master Science degree at Universidad Javeriana (1995), and specialization training in immunochemistry and cellular immunology at National Institute of Health from Tokyo (Japan, 1986). Her primary field is Bacteriologist. Her studies in cell Biology of Plasmodium began with profesor Winograd E. at the Instituto Nacional de Salud (Bogotá), Wiser M., as consultor and co-investigator from Tulane University. She continued searching the cell Biology of Plasmodium at National University of Colombia (2005- ) in collaboration with Biofísica y Biología de membranas, Dr. Camacho M. at Centro Internacional de Física, Public Health Department
at Faculty of Medicine. Her group published recently aspects related to, identification of antigen named Pf68 kDaPlasmodium falciparum resident protein of and specialized domain of the endoplasmic reticulum, or Plasmodium export compartment (PEC), PfHSP70-2 and (2020) and Plasmodium WD40 repeat-containing protein-1 (PlasWD40-1) identified from a cDNA expression library screened with Mab7 (2021), both proteins hypothesized as share a common epitope recognized by a same monoclonal antibody, mAb7 (doctoral thesis, 2019); besides, a study of release merozoites process from its host by photoconversion fluorescent compound to electron microscopy (2011), and characterization of proteins localized to a subcellular compartment associated with an alternate secretory pathway of the malaria parasite (2003). Currently, she is a Ph.D. researcher and professor of the Department of public health Faculty of Medicine at Universidad Nacional de Colombia.

Abstract:
The identification of novel physiological regulators that stimulate energy expenditure through brown adipose tissue (BAT) activity in substrate catalysis is of utmost importance to understand and treat metabolic diseases. Myoglobin (MB), known to store or transport oxygen in heart and skeletal muscles, has recently been found to bind fatty acids with physiological constants in its oxygenated form (i.e., MBO2). Here, we investigated the in vivo effect of MB expression on BAT activity. In particular, we studied mitochondrial function and lipid metabolism as essential determinants of energy expenditure in this tissue. We show in a MB-null (MBko) mouse model that MB expression in BAT impacts on the activity of brown adipocytes in a twofold manner: i) by elevating mitochondrial density plus maximal respiration capacity, and through that, by stimulating BAT oxidative metabolism along with the organelles` uncoupled respiration; and ii) by influencing the free fatty acids pool towards a palmitate-enriched composition and shifting the lipid droplet (LD) equilibrium towards higher counts of smaller droplets. These metabolic changes were accompanied by the up-regulated expression of thermogenesis markers UCP1, CIDEA, CIDEC, PGC1-α and PPAR-α in the BAT of MB wildtype (MBwt) mice. Along with the emergence of the “browning” BAT morphology, MBwt mice exhibited a leaner phenotype when compared to MBko littermates at 20 weeks of age. Our data shed novel insights into MB’s role in linking oxygen and lipid-based thermogenic metabolism. The findings suggest potential new strategies of targeting the MB pathway to treat metabolic disorders related to diminishing energy expenditure.
Biography:
Dr. Thomas A. Gorr: from 1982-1988:Study of Biology, in Philipps-University Marburg, Marburg, Germany; from 1989-1993:PhD thesis in Protein Chemistry at the Max-Planck-Institute for Biochemistry, Martinsried, Germany; in 1994:Dr. rer. nat. (PhD), Ludwig-Maximilians-University, Munich, Germany; from 1994-2004:postdoctoral stay in USA: a) UT Austin TX; b) Harvard Medical School; in 2005-today:Leader of independent hypoxia/metabolism research group; Univ. Zurich; 2014:Habilitation (PD) in Comparative Physiology, Vetsuisse Faculty, University Zurich.

Abstract:
Injuries to the cell membrane of cancer cells, which are caused from invasive behavior, enhanced membrane dynamic and metabolic stress pose lethal threats to cancer cells. However, cancer cells cope by activating their plasma membrane repair system, which depends on mechanisms to remove damaged membrane by excision, internalization by endocytosis or reorganization of actin around the hole to reseal the wound. Proteins belonging to the annexin family are often found highly expressed in various cancer types and are characterized by their Ca2+-dependent binding to anionic phospholipids in the plasma membrane. Annexin family members share the ability to glue adjacent membranes together during wound healing but our recent results show that they play roles that are more specific in membrane repair by regulation of membrane excision, shedding, and induction of membrane curvature in cancer cells. Our findings open a novel avenue to target cancer cells by compromising annexin mediated plasma membrane repair. Here, novel molecular aspects of targeting the membrane repair system in cancer cells by phenothiazines, which alter plasma membrane properties and sensitize to membrane injury by inhibiting annexin-mediated repair will be presented.
Biography:
Dr. Jesper Nylandsted is Group Leader at the Danish Cancer Society Research Center in Copenhagen. His work focuses on alternative death pathways and repair mechanisms in cancer cells and novel approaches to target these processes. Using biophysical methods and live cell imaging, his group has revealed fundamental processes in cell death signalling and plasma membrane repair mechanisms of cancer cells.

Abstract:
Metastatic small cell lung cancer (SCLC) is not curable. While SCLC is initially sensitive to chemotherapy, remissions are short-lived. The relapse is induced by chemotherapy- selected tumor stem cells, which express the AC133 epitope of the CD133 stem cell marker. We studied the effectiveness of AC133-specific CAR T cells post-chemotherapy using human primary SCLC and an orthotopic xenograft mouse model. AC133-specific CAR T cells migrated to SCLC tumor lesions, reduced the tumor burden, and prolonged survival in a humanized orthotopic SCLC model, but were not able to entirely eliminate tumors. We identified CD73 and PD-L1 as immune-escape mechanisms and combined PD-1-inhibition and CD73-inhibition with CAR T cell treatment. This triple-immunotherapy induced cures in 25% of the mice, without signs of graft-versus-host disease or bone marrow failure. AC133+ cancer stem cells and PD-L1+CD73+ myeloid cells were detectable in primary human SCLC tissues, suggesting that patients may benefit from the triple-immunotherapy. We conclude that the combination of AC133-specific CAR T cells, anti-PD-1-antibody and CD73-inhibitor specifically eliminates chemoresistant tumor stem cells, overcomes SCLC-mediated T cell inhibition, and might induce long-term complete remission in an otherwise incurable disease.
Biography:
Dr. Sanaz Taromi current Position: Professor in Faculty Medical and Life Sciences University Furtwangen. Group Leader in Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center – University of Freiburg, Germany. Research: She is molecular biologist; her research is concentrated on the development of novel CAR T cell-based approaches against SCLC. She is conducting preclinical studies on the mechanisms of SCLC metastasis formation, inhibitory tumor microenvironment, and stem cell-based resistance and T cell infiltration of solid tumors.

Abstract:
Graves’ disease is one of the most common autoimmune diseases affecting Indians, accounting for 50–80% of hyperthyroidism cases. The major morbidities associated with Graves’ disease are universally acknowledged. Thus, preventing metabolic syndrome could lead to a reduction in the country’s disease burden. Objectives: The objectives of this study are to determine the incidence of metabolic syndrome in patients who have achieved clinical and biochemical euthyroid status after treatment, as well as to evaluate the clinical and biochemical parameters that lead to metabolic syndrome in Graves’ disease patients. Materials and methods: This is a prospective observational study of 96 Graves’ disease patients in a tertiary care hospital in rural Kolkata. The study participants were chosen using systemic random sampling. The clinical and biochemical parameters of the participants in the study were evaluated. The paired t tests were used. A P value of 0.05 was regarded as significant. Results: After achieving euthyroid status, 36% of the study population developed metabolic syndrome according to International Diabetes Federation (IDF) criteria.93.5% of those who developed metabolic syndrome had a normal BMI at the time of Graves’ disease diagnosis. Conclusion: Following a healthy lifestyle, which includes healthy eating habits, proper drug compliance, and follow-up, may help to prevent the occurrence of metabolic syndrome. By lowering the risk of developing metabolic syndrome, patients may be able to lead a healthier lifestyle by keeping the disease under control.
Biography:
Dr. Jinesh Sengupta completed his MBBS from Medical College and Hospital, Kolkata passed MD General Medicine from R G Kar Medical College, Kolkata with gold medal. Currently he had posted at Nayagram Super Speciality Hospital as Senior Resident.

Abstract:
RNA binding proteins (RBPs) are highly abundant in eukaryotic cells and govern essential aspects of cellular function through interactions with their mRNA substrates and proteins. These ribonucleoprotein (RNP) complexes may further assemble into membraneless condensates, referred to as RNP granules, to regulate the localization and functions throughout RNA splicing, transcription and stability. The dysregulation of RBPs such as genetic mutations can lead to the formation of pathologic condensates. Dysregulated RNP granules have been linked to neuromuscular degenerative disease, but haven’t been linked to cardiomyopathies. RNA binding motif 20 (RBM20) is one of the RBPs that is primarily expressed in heart muscle tissue. RBM20 is a major splicing regulator of gene TTN, encoding a giant sarcomere protein titin that plays a determinant role of ventricular wall stiffness. Deficiency of RBM20 in animal models resulted in larger titin isoform expression and dilated cardiomyopathy. Recently, our lab reported that RBM20 genetic mutations in arginine/serine (RS) domain led to impaired nuclear retention and transport of RBM20 from the nucleus to the cytoplasm. Re-localization of RBM20 in the cytoplasm promoted RNP granules formation. Our mutation knock-in (KI) mouse model demonstrated severe dilated cardiomyopathy and heart failure. The mice carrying the mutation had about 50% death rate at about 8-week-old. We also observed that differentially expressed and spliced genes were associated with arrhythmia, cardiomyopathy, and sudden death. KI mice showed a reduction of diastolic stiffness and impaired contractility at both the left ventricular chamber and cardiomyocyte levels. Our results indicate that the RBM20 mutation leads to RNP granules causing severe heart failure and early death. This finding confirms the novel concept that RBM20 cardiomyopathy is a RNP granule disease.
Biography:
Dr. Wei Guo received his bachelor’s degree in Biological Science in 1999 and his Ph.D. degree in Molecular and Cellular Biology in 2004 at China Agriculture University. He then moved to University of Wisconsin-Madison for his postdoctoral training from 2005 to 2010. After his postdoc training, he worked as a scientist in Medical School at University of Wisconsin-Madison from 2010 to 2013. He then became a faculty member at Department of Animal Science at University of Wyoming from 2013 to 2019. He currently is a tenure-track faculty member at Department of Animal and Dairy Sciences at University of Wisconsin-Madison. He received several scientific presentation award and Outstanding Young Investigator Award at University of Wyoming in 2018. He has published over 50 peer-reviewed articles and book-chapters. He serves as a journal reviewer for over 30 peer-reviewed journals as well as a grant reviewer in study sections for American Heart Association, NASA Human Research Program, and NIH etc. His research interests is to define the molecular and cellular mechanisms of RNA binding proteins in muscle function and disease through performing rigorous and clinically relevant research. His research is supported by the National Institutes of Health (NIH), the American Heart Association (AHA) and the United States Department of Agriculture (USDA)-NIFA Hatch grant.

Abstract:
About 7 % of men worldwide have problems to conceive, a situation that is related to 20-50 % cases of infertility. Besides, between 30-80 % of this affection has been related with oxidative stress, a factor that is also connected with genetic damage, such as microdeletions or DNA fragmentation. In this context, it is known that cadmium (Cd) produce health alterations related with its capacity to originate oxidative stress, and that beta-caryophyllene (BC) is a bicyclic sesquiterpene with beneficial activities such as genoprotection and antioxidation, mainly studied in somatic cells. Therefore, the aim of the present work was to evaluate the protective capacity of BC on the genotoxicity and sperm quality damage induced by Cd. We used CD1 male mice organized in six groups with 5 individuals each, using the intragastric route for the administration. In the assay corn oil and BC was administered for 11 days. The groups were as follows: one group received corn oil, other received corn oil and at day 5 a single administration of Cd (3 mg/kg), the next group was administered BC (400 mg/kg), and three last groups were administered BC 20, 200, and 400 mg/kg as well as 3 mg/kg of Cd in the day 5. At day 11, sperms, spermatids, and testes were obtained to determine sperm quality, antigenotoxicity (comet assay and micronucleus test), and antioxidant of BC capacity (lipids and proteins). The obtained results showed no damage by BC in the indicated parameters, and protection with all doses of BC against the Cd damage, showing a better effect with the high dose. With such dose, a complete protection on sperm concentration and morphology damage was observed, in sperm motility and viability the protection was higher than 74 %. BC data with the comet assay showed a reduction of 92 % respect to the Cd effect, and in micronuclei the reduction obtained with BC reached 83 %. In sperm lipoperoxidation the protection by BC was complete, and regarding data of testicular lipid and protein oxidation the protection by BC was higher than 85 %. Histological damage was also improved by BC. Therefore, our study demonstrated a strong beneficial effect of BC over the damage induced by Cd, probably mediated by its antioxidant potential.
Biography:
Dr. Beatriz A. Espinosa-Ahedo is a Biochemical Engineer by the Technological Institute of Ecatepec, MsC, and PhD by the National Polytechnic Institute (México). She has experience in the Genetics Department of the General Hospital of México. And also she has twelve years of experience in assisted reproduction in a Laboratory of Andrology. Her Research interest are genetics and reproductive toxicology.

Abstract:
Introduction: Ectodermal dysplasias (ED) are a group of approximately 200 clinical and congenital syndromes characterized by alterations in the development and homeostasis of two or more ectodermal structures. There is one case per one million people and one case per 17000 newborns worldwide. The molecular causes of ED involve many genes and multiple developmental pathways. The genes causing ED act through pathogenetic mechanisms in the EDA/EDAR/EDARADD signalling pathway and regulatory pathways such as NEMO, WNT, TP63, EVC2, among others. The clinical presentation is characterized by hypohidrosis, hypodontia or anodontia, hypotrichosis, dermal alterations, craniofacial and limb malformations, and other clinical manifestations. Objective: The aim of our research was to identify the mutational spectrum in genes involved in the EDA, WNT and p63 signalling pathways associated with clinical alterations in the development of ectodermal structures in Mexican patients diagnosed with ectodermal dysplasia by whole exome sequencing (WES) analysis.Materials and methods: Genomic DNA were extracted from peripheral blood samples of ten mexican patients, with two or more clinical features related to structures of ectodermal origin. Subsequently, bioinformatic analysis of WES was performed, to determine exome sequencing quality, the FastQC software was used, then, the exomes were mapped against the reference genome GRCh38 with the BWA programme, filtered, realigned and the variants were identified and functionally classified in comparison against the database with the GATK and FUNCOTATOR software, finally, those variants were determined using databases such as ClinVar, OMIM, gnomAD, among others. Finally, the results were confirmed by Sanger sequencing.
Results: The bioinformatic analysis of WES supported the clinical diagnosis of Ellis Van Crevel syndrome, Curry-Hall syndrome, Ritscher-Schinzel 1 syndrome, hypohidrotic ectodermal dysplasia, EEC, SHFM4 and epidermolysis bullosa. Four patients required clinical re-evaluation to perform proper genotype-phenotype correlation.
Conclusions: We identified 6 pathogenic variants: three missense mutations in TP63, WASHC5 and EDA genes, two frame shift mutations in EVC2 gene, and one nonsense mutation in EVC2 gene, of which, five mutations are not reported in the databases, and one was previously reported as pathogenic.
Biography:
Dr. Nancy Negrete-Torres1 is a Medical Doctor from the Universidad Nacional Autónoma de México, and MsC from the Instituto Politécnico Nacional (México). She Participated in various local Meetings. Her interest are clinical genetics, molecular biology, and bioinformatics. The present project is being developed for my master’s thesis and in collaboration with the Medical Surgeon Career of the Facultad de Estudios Superiores UNAM and the Escuela Nacional de Ciencias Biologicas IPN with the support of Dr. Glustein Pozo Molina and Dr. Isela Álvarez González, and the Centro Médico Nacional 20 de Noviembre, ISSSTE. She has participated in the Program for the Human Development Through Education and Scientific Research in Medicine.

Abstract:
About 7 % of men worldwide have problems to conceive, a situation that is related to 20-50 % cases of infertility. Besides, between 30-80 % of this affection has been related with oxidative stress, a factor that is also connected with genetic damage, such as microdeletions or DNA fragmentation. In this context, it is known that cadmium (Cd) produce health alterations related with its capacity to originate oxidative stress, and that beta-caryophyllene (BC) is a bicyclic sesquiterpene with beneficial activities such as genoprotection and antioxidation, mainly studied in somatic cells. Therefore, the aim of the present work was to evaluate the protective capacity of BC on the genotoxicity and sperm quality damage induced by Cd.We used CD1 male mice organized in six groups with 5 individuals each, using the intragastric route for the administration. In the assay corn oil and BC was administered for 11 days. The groups were as follows: one group received corn oil, other received corn oil and at day 5 a single administration of Cd (3 mg/kg), the next group was administered BC (400 mg/kg), and three last groups were administered BC 20, 200, and 400 mg/kg as well as 3 mg/kg of Cd in the day 5. At day 11, sperms, spermatids, and testes were obtained to determine sperm quality, antigenotoxicity (comet assay and micronucleus test), and antioxidant of BC capacity (lipids and proteins).The obtained results showed no damage by BC in the indicated parameters, and protection with all doses of BC against the Cd damage, showing a better effect with the high dose. With such dose, a complete protection on sperm concentration and morphology damage was observed, in sperm motility and viability the protection was higher than 74 %. BC data with the comet assay showed a reduction of 92 % respect to the Cd effect, and in micronuclei the reduction obtained with BC reached 83 %. In sperm lipoperoxidation the protection by BC was complete, and regarding data of testicular lipid and protein oxidation the protection by BC was higher than 85 %. Histological damage was also improved by BC. Therefore, our study demonstrated a strong beneficial effect of BC over the damage induced by Cd, probably mediated by its antioxidant potential.
Biography:
Dr. Isela Alvarez-Gonzalez obtained her MsC. and PhD. from the National School of Biological Sciences, National Polytechnic Institute (Mexico). She is a Professor of Genetics and Toxicological Genetics at the Chemico-Biological Postgraduate Program in the indicated institution. She has participated in 59 International Meetings and 69 National Meetings. Author or co-author of 74 scientific articles published in JCR indexed journals. Her main interests are in the fields of mutagenesis, antimutagenesis, and chemoprevention.

Abstract:
Background: Malaria is a major public health threat in tropical and subtropical countries. Rapid diagnostic in resource-limited settings remains a major obstacle to eliminate malaria, especially with the emergence of Plasmodium knowlesi. The present study aims to develop a method for rapid diagnosis of human malaria using loop-mediated isothermal amplification (LAMP) coupled with lateral flow (LF). To simplify the sample preparation process, a paper-based nucleic acid extraction method was utilized in this study. The entire procedure from sample preparation to diagnosis takes approximately 1 hour and 15 minutes to complete, LAMP-LF assay exhibited high sensitivity, as the detection limit was 5 parasite/uL for all five Plasmodium species. Clinical sensitivity was 94.73% using 57 malaria samples and specificity was 100% using 42 healthy samples. Combined with a simple nucleic acid extraction step, this optimized LAMP-LF method can be potentially developed as point-of-care diagnostic tool in future.
Biography:
Dr. Yee Ling Lau is at present the Head of the Department of Parasitology, Faculty of Medicine at University of Malaya (UM). Her scientific career has been dedicated to the study of protozoan parasites, including Plasmodium knowlesi and Toxoplasma gondii, the causative agents of malaria and toxoplasmosis, respectively. These parasitic diseases exact enormous social and economic burdens. Her research interest mainly focuses on using molecular methods for the detection and characterization of these parasites infecting humans and animals. She has collaborated with local and international researchers, leading to publication of more than 180 ISI journals, with total citations index of 2598 and H-index of 27. Since 2009, 13 Masters and 17 PhDs have completed their studies with success under her guidance. Currently, they are 4 Masters and 8 PhDs under her supervision. Currently, she is the editor-in-chief for the Journal of Health and Translational Medicine (JUMMEC) for University of Malaya, editor of Asia Pacific Journal of Molecular Biology & Biotechnology and associate editor of BMC Infectious Diseases. She has been an active member of the Malaysian Society of Parasitology and Tropical Medicine (MSPTM). She was a council member of the MSPTM in year 2018-2019. She is also active in the Malaysian Society for Biochemistry and Molecular Biology (MSBMB). She was the Honorary Secretary of the MSBMB in 2017-2019 and the current President. She has been awarded University of Malaya Excellent Service Award three times in 2011, 2013 and 2015. She was awarded MSPTM Nadchadtram Medal in 2014. She has also been awarded a few times for her innovation in research including the Grand Prize in National Exclusive Innovation Challenge Award 2018.

Abstract:
Natural products and their derivatives have long been recognized as a valuable source of therapeutic agents and they constitute a significant portion of currently approved drugs. Some of the challenges in the field of natural product research include early detection of ingredients of interest and dereplication of already known compounds in plant extracts. In an attempt to overcome these obstacles, we employ mass spectrometry-based molecular networking techniques for rapid identification of known metabolites and detection of related structures by organizing MS/MS spectra based on chemical similarity. The LC-MS/MS spectra of the plant fractions are acquired on a high-resolution Q-TOF instrument and analyzed using Global Natural Products Social Molecular Networking (GNPS) web-based platform. The molecular networks are visualized in Cytoscape software. In our lab, several plants were subjected to this analysis. In particular, molecular networking of Uvaria rufa (Annonaceae), revealed the presence of acetogenins and polyoxygenated cyclohexene derivatives. Compounds of the acetogenin class are known for their strong cytotoxic activity and have been proposed as anticancer drug leads. Current research efforts are focused on isolation and structure elucidation of new compounds, followed by bioactivity testing, with the goal of finding novel bioactive lead structures.
Biography:
Dr. Aleksandra Gurgul is a PhD candidate in the Pharmacognosy program at the University of Illinois at Chicago, USA. She received her Bachelor and Master’s Degrees in Biology at Jagiellonian University in Poland. Her current research in Prof. Chun-Tao Che’s Lab focuses on the isolation and structure elucidation of phytochemicals using state-of-the-art chromatographic and spectroscopic techniques, as well as biological evaluation of natural products.

Abstract:
In eukaryotic cells, transcription and translation processes are physically separated by the nuclear envelope (NE). Newly transcribed mRNAs must be exported to the cytoplasm for protein synthesis, while some proteins require to be imported into the nucleus to fulfill their nuclear functions. This nucleocytoplasmic transport (NCT) across the NE is tightly regulated and is critical for maintaining cellular homeostasis. Its dysregulation leads to aging and many neurological diseases, including amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and Alzheimer’s disease (AD). To decipher the pathophysiological mechanisms underlying NCT-impaired neurological diseases, the examination of NCT activities at the single cell level is critical. Recently, we reported the techniques for measuring the nuclear transport of both mRNA and protein cargos. Fluorescent In Situ Hybridization (FISH) coupled with oligodT probes were used to measure the distribution of Poly(A) RNAs (mRNA). A dual reporter (GFP-NES and RFP-NLS) was used to examine the protein nuclear transport. The approaches together with imaging analysis enable us to systematically quantify the NCT activities in cultured neurons. We modele movement disorder dystonia using patient-derived motor neurons (MNs), which have been generated via direct conversion from patient fibroblasts and the differentiation of induced pluripotent stem cells (iPSCs). We first reported the disease dependent cellular deficits of dystonia in patient-derived neurons, including deformed nucleus, mislocalized proteins, and impaired nucleocytoplasmic transport, providing another example of the impairment of NCT in neurological diseases. Our study also demonstrates the high value of patient-derived neurons in modeling neurological diseases.
Note: The techniques for the nucleocytoplasmic transport measurement and the generation of patientderived neurons can be found in our recent publications (PMID: 35300000, 34746870, 34536661,
34380890, 33468570, 33510083, 32783653, 32317929).
Biography:
Dr. Baojin Ding received his bachelor’s degree in Medicine (MD equivalent) and master’s degree in Clinical Laboratory in China. After he received PhD in Biochemistry and Molecular Biology from Louisiana State University (LSU), he did postdoctoral training in Neuroscience at the UMass Medical School and worked as a research faculty in the UT Southwestern Medical Center. In 2018, he obtained as a  Assistant Professor (tenure-track) at the University of Louisiana at Lafayette and then relocated to Louisiana State University Health Sciences Center at Shreveport. The research at his  laboratory is
focusing on Molecular and Cellular Neuroscience and Neurological Diseases, and currently funded by NIH and DoD.

Abstract:
Background: With advent of Hyperthermic Intraperitoneal chemotherapy, the 5-yr survival improved significantly in advanced ovarian cancer. HIPEC might have role in ovarian tumor-microenvironment. Methodology: We included 30 patients with FIGO stage III to IV A advanced Epithelial ovarian cancer. We have seen the expression of FOXp3, RORɣ, Interleukin-10 and IL-17 in tumor and PBMC before and after HIPEC in and compared the changes of expression through FCM and RT-PCR.
Results: There was highest expression of FOXp3 mRNA in recurrent group followed by upfront and interval. There was statistically significant decrease in FOXp3 at four weeks in three subgroups. There was an increase in ROR-ɣ in 4 weeks in upfront and interval groups. Conclusions: HIPEC might have some role on ovarian tumor microenvironment, as we found in the expression of FOXp3 and Th17, thereby increasing the survival.
Biography:
Dr M D Ray, MS, FRCS, FACS, PhD, an eminent onco-surgeon in premier institute, AIIMS, Delhi, India. He is a teacher, guide of MCh, Surgical Oncology superspeciality and PhD in clinico Molecular Oncology. He is an eminent Indian author in his profession as well as in literature. He published more than 110 papers ,11 Medical books and 21 books in literature. He believes ‘Humanity is the best religion.

Abstract:
Background & Aims: Maternal liver exhibits robust adaptations to pregnancy to accommodate the metabolic needs of developing and growing placenta and fetus by largely unknown mechanisms. We found that achaete-scute homolog-like 1 (Ascl1), a gene encoding a basic helix-loop-helix transcription factor essential for neuronal development, is highly activated in maternal hepatocytes during the second half of gestation in mice. Methods: To investigate whether and how Ascl1 plays a pregnancy-dependent role, we deleted the Ascl1 gene specifically in maternal hepatocytes from mid-gestation until term. Results: As a result, we identified multiple Ascl1-dependent phenotypes. Maternal livers lacking Ascl1 exhibited aberrant hepatocyte structure, increased hepatocyte proliferation, enlarged hepatocyte size, reduced albumin production, and elevated release of liver enzymes, indicating maternal liver dysfunction. Simultaneously, maternal pancreas and spleen and the placenta displayed marked overgrowth; and the maternal ceca microbiome showed alterations in relative abundance of several bacterial subpopulations. Moreover, litters born from maternal hepatic Ascl1-deficient dams experienced abnormal postnatal growth after weaning, implying an adverse pregnancy outcome. Mechanistically, we found that maternal hepatocytes deficient for Ascl1 exhibited robust activation of insulin-like growth factor 2 expression, which may contribute to the Ascl1-dependent phenotypes widespread in maternal and uteroplacental compartments. Conclusions: In summary, we demonstrate that maternal liver, via activating Ascl1 expression, modulates the adaptations of maternal organs and the growth of the placenta to maintain a healthy pregnancy. Our studies reveal Ascl1 as a novel and critical regulator of the physiology of pregnancy.
Biography:
Dr. Guoli Dai is an Associate Professor in the Department of Biology, School of Science, Center for Developmental and Regenerative Biology, in Indiana University-Purdue University Indianapolis (IUPUI). His research interest focuses on molecular and cellular mechanisms controlling liver growth and regeneration.

Abstract:
Ovulation, which is induced by the ovulatory luteinizing hormone (LH) surge in vertebrates, is a dynamic process that results in a discharge of one or more fertilizable oocytes from the ovarian follicle into the ovarian cavity or into the abdominal cavity. Follicle rupture is a core event of the ovulatory process and has been the subject of intensive investigation. Prostaglandins are well known to be central regulators of vertebrate ovulation. Studies addressing the role of prostaglandins in mammalian ovulation have established that they are involved in the processes of oocyte maturation and cumulus oocyte complex expansion. In contrast, despite the first indication of the role of prostaglandins in teleost ovulation appearing 40 years ago, the mechanistic background of their role has long been unknown. However, studies conducted on the teleost medaka over the past decade have provided valuable information. Emerging evidence indicates a critical role of prostaglandin E2 and its receptor subtype Ptger4b in the process of follicle rupture. In addition, our studies have revealed that activation of the melatonin/melatonin receptor system in the ovulating follicle is required for the prostaglandin E2-mediated follicle rupture process. In this talk, we summarize studies addressing the role of prostaglandins in teleost ovulation and describe recent advances. To help understand differences from and similarities to ovulation in mammalian species, the findings on the roles of prostaglandins in mammalian ovulation are discussed in parallel.
Biography:
Dr. Takayuki Takahashi, Ph.D., Emeritus Professor of Hokkaido University, Japan In 1979 Ph.D. in Zoology (Hokkaido University) from 1980-1986 Research Associate, Protein Studies Lab at Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA from 1987-1993 he is an Assistant Professor, Faculty of Science, University of Tokyo, Japan from 1993-2016 he is an Professor, Faculty of Science, Hokkaido University, Japan from 2016-2019 he is a
Research Professor, Hokkaido University, Japan.His research activities are in the field of reproductive biology of vertebrates including fish. In particular, his laboratory has been closely associated with ovulation studies using a teleost medaka by cellular and molecular biological approaches. His final goal is to get insights into the evolutional aspect of ovulation in the animal kingdom. Achievements: They were the first to report that, using the teleost medaka, (i) MMPs and plasminogen activator/plasmin are involved in follicle rupture during ovulation (PNAS, 2005; Biol. Reprod., 2012, 2015). In addition, they studies showed that (ii) many ovulation-related-genes are induced by the surge of LH at ovulation (PLoS ONE, 2013; Biol. Reprod., 2014; MCE, 2017), (iii) activation of the prostaglandin E2 and the receptor system is required for follicle rupture (MCE, 2011, 2012, 2017; Biol. Reprod., 2016), and (iv) follicle rupture during ovulation is the process which proceeds under precise endocrine control (MCE, 2017; Reproduction, 2019; cells, 2019).
Award
In 2010, Prize from the Zoological Society of Japan
“Discovery of ovulatory proteases and elucidation of follicle rupture mechanism in teleost medaka”