Day2

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”

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:
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:
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:
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:
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:
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:
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. 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:
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:
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:
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:
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:
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:
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:
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
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:
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:
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:
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:
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:
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.