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第六次国际暨第十五次全国膜生物学学术研讨会

作者： Jichun Yang Department of Physiology and Pathophysiology School of Basic Medical SciencesKey Laboratory of Molecular Cardiovascular Sciences of the Ministry of EducationCenter for Non-coding RNA MedicinePeking University Health Science Center

Mitochondrial dysfunction including decreased ATP production and increased ROS production plays important roles in the pathogenesis of *** the past decade,our research had been focused on determining the roles and mechanisms of ATP production in the regulation of hepatic gluconeogenesis and *** hepatocytes,ATP can be released to function as a signaling molecule by binding to and activating P2 receptor (ATP receptor).ATP activates P2X receptor subtype to increase influx of extracellular calcium,and activates P2Y receptor subtype to increase calcium release from internal calcium storage such as ***,ATP-triggered slight increase in cellular calcium activates CaM to phosphorylate

关键词： ATP-P2 receptor signaling transduction in the regulation of glucose and lipid metabolism

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Methane and Co2 Consumption from a Synthetic Waste Gas by Microbial Communities in Enriched Seawater

SSRN

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SSRN 2024年

作者： Frigaard, Niels-Ulrik Seemann, Stefan E. Marine Biological Section Department of Biology University of Copenhagen Helsingør Denmark Center for non-coding RNA in Technology and Health Department of Veterinary and Animal Sciences University of Copenhagen Frederiksberg Denmark

Methane (CH4) and carbon dioxide (CO2) occur as undesirable waste products in carbon-based fuel productions. Bothgases are major greenhouse gases with CH4 being much more potent than CO2. For this reason, excess CH4 from varioussources is often flared into CO2 rather than releasing the CH4 into the atmosphere, however, some CH4 is still emitteddue to the inefficiency of flare combustion. We have explored how natural microbial communities can be manipulatedinto consuming both CH4 and CO2 from a gas stream and converting the gases into microbial biomass. Natural seawaterwas enriched with inorganic nutrients and injected with a continuous gas stream containing CH4 (4.7% v/v) and CO2(1% v/v) over a period of several days, either in the dark or in the light. Microbial communities established thatcontained methanotrophic bacteria consuming CH4, and cyanobacteria and microalgae consuming CO2. The measureof chemotaxonomic markers revealed that the growth of phototrophs increased greatly only in the light with an earlydominance by cyanobacteria later overtaken by microalgae, and that the growth of methanotrophs increased greatlyonly in the dark. The microbial communities were characterized using near-full-length 16S/18S rrna gene ampliconsequencing with the Nanopore technology. In the incubated cultures, the microbial diversity was drastically lower ascompared to the natural communities. The most abundant microalgae were green algae belonging to Picochlorum,Tetraselmis, Chlamydomonas, and Nannochloris, and the most abundant cyanobacteria were related to Geitlerinemasp. PCC 7105, Symphothece sp. PCC 7002 and Cyanobium sp. PCC 6307 (based on the SILVA reference database).Methylomicrobium and Methylobacter were the most abundant methanotrophs in the dark-incubated cultures, whereasMethylomonas methanica was identified as the single methanotroph with notable abundance under light ***, for optimal CH4 and CO2 consumption it may be necessary to physically separate

关键词： Microalgae

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EDD enhances cell survival and cisplatin resistance and is a therapeutic target for epithelial ovarian cancer

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CARCINOGENESIS 2014年第5期35卷 1100-1109页

作者： Bradley, Amber Zheng, Hui Ziebarth, Angela Sakati, Wayne Branham-O'Connor, Melissa Blumer, Joe B. Liu, Yuying Kistner-Griffin, Emily Rodriguez-Aguayo, Cristian Lopez-Berestein, Gabriel Sood, Anil K. Landen, Charles N., Jr. Eblen, Scott T. Med Univ S Carolina Dept Cell & Mol Pharmacol & Expt Therapeut Charleston SC 29425 USA Univ Alabama Birmingham Dept Obstet & Gynecol Birmingham AL 35233 USA Med Univ S Carolina Dept Med Div Biostat & Epidemiol Charleston SC 29425 USA Med Univ S Carolina Hollings Canc Ctr Charleston SC 29425 USA Univ Texas MD Anderson Canc Ctr Dept Expt Therapeut Houston TX 77230 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77230 USA Univ Texas MD Anderson Canc Ctr Dept Canc Biol Houston TX 77230 USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol & Reprod Med Houston TX 77230 USA

We show that the E3 ubiquitin ligase EDD/UBR5 regulates both survival and cisplatin resistance in ovarian cancer cells and is a novel therapeutic target for ovarian *** E3 ubiquitin ligase EDD is overexpressed in recurrent, platinum-resistant ovarian cancers, suggesting a role in tumor survival and/or platinum resistance. EDD knockdown by small interfering rna (sirna) induced apoptosis in A2780ip2, OVCAR5 and ES-2 ovarian cancer cells, correlating with loss of the prosurvival protein myeloid cell leukemia sequence 1 (Mcl-1) through a glycogen synthase kinase 3 beta-independent mechanism. Sirna to EDD or Mcl-1 induced comparable levels of apoptosis in A2780ip2 and ES-2 cells. Stable overexpression of Mcl-1 protected cells from apoptosis following EDD knockdown, accompanied by a loss of endogenous, but not exogenous, Mcl-1 protein, suggesting that EDD regulated Mcl-1 synthesis. Indeed, EDD knockdown induced a 1.87-fold decrease in Mcl-1 messenger rna and EDD transfection enhanced murine Mcl-1 promoter-driven luciferase expression 5-fold. To separate EDD survival and potential cisplatin resistance functions, we generated EDD shrna stable cell lines that could survive initial EDD knockdown and showed that these cells were 4- to 21-fold more sensitive to cisplatin. Moreover, transient EDD overexpression in COS-7 cells was sufficient to promote cisplatin resistance 2.4-fold, dependent upon its E3 ligase activity. In vivo, mouse intraperitoneal ES-2 and A2780ip2 xenograft experiments showed that mice treated with EDD sirna by nanoliposomal delivery [1,2-dioleoyl-sn-glycero-3-phophatidylcholine (DOPC)] and cisplatin had significantly less tumor burden than those treated with control sirna/DOPC alone (ES-2, 77.9% reduction, P = 0.004;A2780ip2, 75.9% reduction, P = 0.042) or control sirna/DOPC with cisplatin in ES-2 (64.4% reduction, P = 0.035), with a trend in A2780ip2 (60.3% reduction, P = 0.168). These results identify EDD as a dual regulator of cell survival and ci

关键词： Animals Antineoplastic Agents/administration & dosage Antineoplastic Agents/pharmacology Apoptosis/drug effects Apoptosis/genetics Cell Line Cell Survival/drug effects Cell Survival/genetics Cisplatin/administration & dosage Cisplatin/pharmacology Disease Models, Animal Drug Resistance, Neoplasm/genetics Female Gene Expression Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Mice Myeloid Cell Leukemia Sequence 1 Protein/genetics Myeloid Cell Leukemia Sequence 1 Protein/metabolism Neoplasms, Glandular and Epithelial/drug therapy Neoplasms, Glandular and Epithelial/genetics Neoplasms, Glandular and Epithelial/metabolism Ovarian Neoplasms/drug therapy Ovarian Neoplasms/genetics Ovarian Neoplasms/metabolism Proteolysis Transcription, Genetic Ubiquitin-Protein Ligases/genetics Xenograft Model Antitumor Assays

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Explainable artificial intelligence reveals novel insight into tumor microenvironment conditions linked with better prognosis in patients with breast cancer

arXiv

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arXiv 2021年

作者： Chakraborty, Debaditya Ivan, Cristina Amero, Paola Khan, Maliha Rodriguez-Aguayo, Cristian Basąǧaoǧlu, Hakan Lopez-Berestein, Gabriel Department of Construction Science University of Texas at San Antonio San AntonioTX United States Department of Experimental Therapeutics University of Texas Md Anderson Cancer Center HoustonTX United States Center for RNA Interference and Non-Coding RNA HoustonTX United States Department of Lymphoma and Myeloma University of Texas Md Anderson Cancer Center HoustonTX United States Evolution Online LLC San AntonioTX United States

We investigated the data-driven relationship between features in the tumor microenvironment (TME) and the overall and 5-year survival in triple-negative breast cancer (TNBC) and non-TNBC (NTNBC) patients by using Explainable Artificial Intelligence (XAI) models. We used clinical information from patients with invasive breast carcinoma from The Cancer Genome Atlas and from two studies from the cbioPortal, the PanCanAtlas project and the GDAC Firehose study. In this study, we used a normalized rna sequencing data-driven cohort from 1,015 breast cancer patients, alive or deceased, from the UCSC Xena data set and performed integrated deconvolution with the EPIC method to estimate the percentage of seven different immune and stromal cells from rna sequencing data. Novel insights derived from our XAI model showed that CD4+ T cells and B cells are more critical than other TME features for enhanced prognosis for both TNBC and NTNBC patients. Our XAI model revealed the critical inflection points (i.e., threshold fractions) of CD4+ T cells and B cells above or below which 5-year survival rates improve. Subsequently, we ascertained the conditional probabilities of ≥5-year survival in both TNBC and NTNBC patients under specific conditions inferred from the inflection points. In particular, the XAI models revealed that a B-cell fraction exceeding 0.018 in the TME could ensure 100% 5-year survival for NTNBC patients. The findings from this research could lead to more accurate clinical predictions and enhanced immunotherapies and to the design of innovative strategies to reprogram the TME of breast cancer patients. © 2021, CC BY-NC-SA.

关键词： rna

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Corrigendum to “A phase II evaluation of aflibercept in the treatment of recurrent or persistent endometrial cancer: A Gynecologic Oncology Group study” [Gynecol Oncol 127 (2012) 538–543 ]

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Gynecologic Oncology 2013年第1期130卷 252-253页

作者： Coleman, Robert L. Sill, Michael W. Lankes, Heather A. Fader, Amanda Nickles Finkler, Neil J. Hoffman, James S. Rose, Peter G. Sutton, Gregory P. Drescher, Charles W. McMeekin, D. Scott Hu, Wei Deavers, Michael Godwin, Andrew K. Alpaugh, R. Katherine Sood, Anil K. Dept. of Gynecologic Oncology & Reproductive Medicine University of Texas M.D. Anderson Cancer Center Houston TX 77030 USA Gynecologic Oncology Group Statistical & Data Center Roswell Park Cancer Institute Buffalo NY 14263 USA Gynecologic Oncology/Clinical Trials Dept. Walter Reed National Military Medical Center — Bethesda Bethesda MD 20889 USA Dept. of Obstetrics & Gynecology Division of Gynecologic Oncology Florida Hospital Cancer Institute Orlando FL 32804 USA Dept. of Obstetrics & Gynecology Division of Gynecologic Oncology The Hospital of Central Connecticut New Britain CT 06050 USA Dept. of Obstetrics & Gynecology Division of Gynecologic Oncology Cleveland Clinic Foundation Cleveland OH 44195 USA Dept. of Obstetrics & Gynecology Division of Gynecologic Oncology Saint Vincent's Hospital Indianapolis IN 46260 USA Pacific Gynecologic Specialists PD Seattle WA 98104 USA Dept. of Obstetrics & Gynecology Division of Gynecologic Oncology University of Oklahoma Oklahoma City OK 73190 USA Dept. of Pathology University of Texas M.D. Anderson Cancer Center Houston TX 77030 USA Dept. of Pathology The University of Kansas Medical Center Kansas City KS 66160 USA Protocol Support Laboratory Fox Chase Cancer Center Philadelphia PA 19111 USA Department of Gynecologic Oncology Center for RNA Interference and Non-Coding RNA University of Texas M.D. Anderson Cancer Center Houston TX 77030 USA Department of Reproductive Medicine Center for RNA Interference and Non-Coding RNA University of Texas M.D. Anderson Cancer Center Houston TX 77030 USA Department of Cancer Biology Center for RNA Interference and Non-Coding RNA University of Texas M.D. Anderson Cancer Center Houston TX 77030 USA

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DNA methylation signatures and coagulation factors in the peripheral blood leucocytes of epithelial ovarian cancer

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Carcinogenesis 2017年第8期38卷 797-805页

作者： Li, Lian Zheng, Hong Huang, Yubei Huang, Caiyun Zhang, Shuang Tian, Jing Li, Pei K.Sood, Anil Zhang, Wei Chen, Kexin Department of Epidemiology and Biostatistics Tianjin Medical University Cancer Institute and Hospital Tianjin 300060 China Department of Urologym National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy of Tianjin Tianjin Medical University Cancer Institute and Hospital Tianjin 300060 China Gynecologic Oncology and Reproductive Medicine Center for RNAi and Non-Coding RNA The University of Texas MD Anderson Cancer Center Houston 77030 TX United States Department of Cancer Biology Wake Forest Baptist Comprehensive Cancer Center Winston-Salem 27157 NC United States

Solid tumors are increasingly recognized as a systemic disease that is manifested by changes in DNA, rna, proteins and metabolites in the blood. Whereas many studies have reported gene mutation events in the circulation, few studies have focused on epigenetic DNA methylation markers. To identify DNA methylation biomarkers in peripheral blood for ovarian cancer, we performed a two-stage epigenome-wide association study. In the discovery stage, we measured genome wide DNA methylation for 485 000 CpG sites in peripheral blood in 24 epithelial ovarian cancer (EOC) cases and 24 age-matched healthy controls. We selected 96 significantly differentially methylated CpG sites for validation using Illumina's Custom VeraCode methylation assay in 206 EOC cases and 205 controls and 46 CpG sites validated in the independent replication samples. A set of 6 of these 46 CpG sites was found by the receiver operating characteristic analysis to have a prediction accuracy of 77.3% for all EOC (95% confidence interval: 72.9-81.8%). Pathway analysis of the genes associated with the 46 CpG sites revealed an enrichment of immune system process genes, including LYST (cg16962115, FDR = 1.24E-04), CADM1 (cg21933078, FDR = 1.22E-02) and NFATC1 (cg06784563, FDR = 1.46E-02). Furthermore, DNA methylation status in peripheral blood was correlated with platelet parameters/coagulation factor levels. This study discovered a panel of epigenetic liquid biopsy markers closely associated with overall immunologic conditions and platelet parameters/coagulation systems of the patients for detection of all stages and subtypes of EOC. © The Author 2017. Published by Oxford University Press.

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A Retrospective Analysis for Different Routes of Administration in Mice-Percutaneous Retro-Orbital, Jugular Catheter, Tail Vein and Femoral Cut Down Injections

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Journal of Biosciences and Medicines 2020年第9期8卷 131-141页

作者： Priyanka Prathipati Cristian Rodriguez-Aguayo Brian L Walton Anil K. Sood Jamieson Greaver Christopher F. Janssen Gabriel Lopez-Berestein Department of Advanced Cardiopulmonary Therapies and Transplantation Center for Advanced Heart Failure University of Texas Health Science Center at Houston Houston TX USA Department of Experimental Therapeutics University of Texas M.D. Anderson Cancer Center Houston TX USA The Center for RNA Interference and Non-Coding RNA University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Cancer Biology University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Gynecology Oncology & Reproductive Medicine University of Texas M.D. Anderson Cancer Center Houston TX USA Interdisciplinary Research Center for Laboratory Animal Medicine and Care University of Texas Health Science Center at Houston Houston TX USA

Liposomes effectively transport fatty proteins to targeted tissues. Laboratory experiments use multiple methods to administer liposomes, but comparison of these methods is not available. In this retrospective study, we characterized and compared four intravenous administration routes (tail vein, jugular catheter, femoral vein and percutaneous retro-orbital injections) in murine models. ApoE^-/- mice were used to compare administration routes. Results indicate that the jugular catheter route delivered the highest amount of liposomes to tissues due to longer period of injections compared to other routes;however, this route failed to remain patent for 8/10 animals. Delivery via tail vein, femoral vein and percutaneous retro-orbital injections resulted in similar accumulation in the organs. When including technical difficulty and expense, percutaneous retro-orbital injections of liposomes are the most convenient and efficacious approach.

关键词： Femoral Vein Jugular Catheter Liposomes Retro-Orbital Tail Vein

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Discovering and Evaluating Organizational Knowledge from Textual Data: Application to Crisis Management

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SSRN 2023年

作者： Grissa, Dhouha Andonoff, Eric Hanachi, Chihab Center for non-coding RNA in Technology and Health Department of Veterinary and Animal Science University of Copenhagen Frederiksberg C1870 Denmark Université Toulouse - Capitole IRIT 2 rue du Doyen Gabriel Marty Toulouse31042 France

Crisis management effectiveness relies mainly on the quality of the distributed human organization deployed for saving lives, limiting damage and reducing risks. Organizations set up in this context are not always predefined and static;they could evolve and new forms could emerge since actors, such as volunteers or NGO, could join dynamically to collaborate. To improve crisis resolution effectiveness, it is first important to understand, analyze and evaluate such dynamic organizations in order to adjust crisis management plans and ease coordination among actors. Giving a textual experience feedback from past crisis, the objective of this paper is to discover the organizational structure deployed in the considered crisis and then evaluate it according to a set of criteria. For that purpose, we combine in a coherent framework text and association rule mining for pattern discovery and annotation, and multi-agent system models and techniques for formally building and evaluating organizational structures. We present the OSminer algorithm that discovers association rules based on relevant textual patterns and then builds an organizational structure including three main relations between actors: power, control and coordination. A real-life case study, a flood crisis hitting the south west of France, serves as a basis for testing/experimenting our solution. The organizational structure, discovered in this case study, has 24 actors. Its evaluation indicates its efficiency, but shows that it is neither robust nor flexible. Our findings highlight the potential of our approach to discover and evaluate organizational structures from a text recording interactions between stakeholders in a crisis context. © 2023, The Authors. All rights reserved.

关键词： Association rules

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Fatty Acid Binding Protein-4 Silencing Attenuates Atherosclerosis Progression by Affecting Macrophage Apoptosis and Autophagy

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Journal of Biosciences and Medicines 2019年第7期7卷 99-109页

作者： Siqin Zhaorigetu Priyanka Prathipati Cristian Rodriguez-Aguayo Brian L. Walton Anil K. Sood Gabriel Berestein-Lopez Department of Pediatric Surgery Center for Advanced Heart Failure University of Texas Health Science Center at Houston Houston TX USA Department of Advanced Cardiopulmonary Therapies and Transplantation Center for Advanced Heart Failure University of Texas Health Science Center at Houston Houston TX USA Department of Experimental Therapeutics The University of Texas M.D. Anderson Cancer Center Houston TX USA The Center for RNA Interference and Non-Coding RNA The University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Cancer Biology The University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Gynecology Oncology & Reproductive Medicine The University of Texas M.D. Anderson Cancer Center Houston TX USA

Background: Atherosclerosis, which is the principal cause of heart attacks and strokes, is the leading cause of death in the United States. Various biological processes such as apoptosis and autophagy are involved in almost every stage of atherosclerosis, which could lead to plaque instability causing stroke and death. Fatty Acid Binding Protein 4 (FABP4) is an adipokine released by macrophages and is involved in multiple disease conditions including stroke. However, the association of FABP4 with macrophage apoptosis and autophagy in atherosclerosis has not been elucidated. We hypothesize that silencing FABP4 protein could be a novel therapeutic approach to attenuate macrophage apoptosis and autophagy thereby minimizing plaque instability in atherosclerosis. Methods: RAW264 mouse macrophage cells were transfected with sirna control liposome quantum dots (QD), siFABP4 liposome QD at the concentration of 150 μg/ml total lipids, or TNF-α at 100 ng/ml. Western blot and reverse phase protein array (RPPA) analysis were completed. Results: Inhibiting the translation of FABP4 blocked the apoptotic pathway as evidenced from the increased expression of anti-apoptotic BCL-xL and BCL-2 along with reduced expression of BAX and activated Caspase 3 levels. Beclin-1 and LC3-II levels were also reduced with knocking down FABP4 indicating the attenuation of autophagy. Conclusion: Targeting FABP4 protects against macrophage processes associated with the progression of atherosclerosis.

关键词： Atherosclerosis Apoptosis Liposomes Macrophages FABP4

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Structure analysis of FAAP24 reveals single-stranded DNA-binding activity and domain functions in DNA damage response

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细胞研究（英文版） 2013年第10期23卷 1215-1228页

作者： Yucai Wang Xiao Han Fangming Wu Justin W Leung Megan G Lowery Huong Do Junjie Chen Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA Laboratory of Non-coding RNA Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China High Magnetic Field Laboratory Chinese Academy of Sciences Hefei Anhui 230031 China Department of Molecular Carcinogenesis The University of Texas MD Anderson Cancer Center Smithville TX 78957 USA

The FANCM/FAAP24 heterodimer has distinct functions in protecting cells from complex DNA lesions such as interstrand crosslinks. These functions rely on the biochemical activity of FANCM/FAAP24 to recognize and bind to damaged DNA or stalled replication forks. However, the DNA-binding activity of this complex was not clearly defined. We investigated how FAAP24 contributes to the DNA-interacting functions of the FANCM/FAAP24 complex by acquiring the N-terminal and C-terminal solution structures of human FAAP24. Modeling of the FAAP24 structure indicates that FAAP24 may possess a high affinity toward single-stranded DNA (ssDNA). Testing of various FAAP24 mutations in vitro and in vivo validated this prediction derived from structural analyses. We found that the DNA-binding and FANCM-interacting functions of FAAP24, although both require the C-terminal (HhH)₂ domain, can be distinguished by segregation-of-function mutations. These results demonstrate dual roles of FAAP24 in DNA damage response against crosslinking lesions, one through the formation of FANCM/FAAP24 heterodimer and the other via its ssDNA-binding activity required in optimized checkpoint activation.

关键词： FAAP24 FANCM DNA binding DNA damage response

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