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      • SCIESCOPUSKCI등재

        Invited Review : Caenorhabditis elegans: A Model System for Anti-Cancer Drug Discovery and Therapeutic Target Identification

        ( Robert A Kobet ),( Xiao Ping Pan ),( Bao Hong Zhang ),( Stephen C Pak ),( Adam S Asch ),( Myon Hee Lee ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.5

        The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.

      • SCIESCOPUSKCI등재

        Caenorhabditis elegans: A Model System for Anti-Cancer Drug Discovery and Therapeutic Target Identification

        Kobet, Robert A.,Pan, Xiaoping,Zhang, Baohong,Pak, Stephen C.,Asch, Adam S.,Lee, Myon-Hee The Korean Society of Applied Pharmacology 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.5

        The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.

      • A bodipy based hydroxylamine sensor

        Sedgwick, Adam C.,Chapman, Robert S. L.,Gardiner, Jordan E.,Peacock, Lucy R.,Kim, Gyoungmi,Yoon, Juyoung,Bull, Steven D.,James, Tony D. The Royal Society of Chemistry 2017 Chemical communications Vol.53 No.75

        <P>With this research, we have developed a bodipy based system as the first “turn-on” fluorescence system for the detection hydroxylamine.</P>

      • Different electronic structure of phosphonyl radical adducts of <i>N</i>-heterocyclic carbenes, silylenes and germylenes: EPR spectroscopic study and DFT calculations

        Sheberla, Dennis,Tumanskii, Boris,Tomasik, Adam C.,Mitra, Amitabha,Hill, Nicholas J.,West, Robert,Apeloig, Yitzhak Royal Society of Chemistry 2010 Chemical Science Vol.1 No.2

        <P>Stable <I>N</I>-heterocyclic carbenes and germylenes were allowed to react with a phosphonyl radical, (<I>i</I>-PrO)<SUB>2</SUB>(O)P&z.rad; (<B>7</B>), generated by photolysis of [(<I>i</I>-PrO)<SUB>2</SUB>(O)P]<SUB>2</SUB>Hg. The products were identified by EPR spectroscopy. An unsaturated carbene (<B>1</B>) and germylene (<B>3</B>) react with <B>7</B> at the divalent atom to give unstable radical products (<I>τ</I><SUB>½</SUB> = 0.2 s). A benzo-annulated carbene (<B>4</B>) and a saturated germylene (<B>6</B>) react with <B>7</B> to give more active radicals. An unsaturated (<B>2</B>) and a saturated silylene (<B>5</B>) undergo rapid reaction (in the dark) with [(<I>i</I>-PrO)<SUB>2</SUB>(O)P]<SUB>2</SUB>Hg to yield unusual silyl phosphites. In these cases only secondary radicals were observed. DFT (PBE0/TZVP//B3LYP/6-31+G(d)) calculations of the radical adducts of the different (C, Si, Ge) unsaturated <I>N</I>-heterocyclic divalent species with the phosphonyl radical show that the unpaired electron is delocalized over the five-membered ring; the spin density on the central atoms decreases in the order C, 39% > Si, 14% > Ge, 2%. These trends can be understood in terms of a zwitterionic structure of the radical adducts. The calculations of the radical adducts of <B>4</B>, <B>5</B> and <B>6</B> with <B>7</B> indicate larger spin density on the central atom, 47%, 58% and 42% on C, Si, Ge, respectively.</P> <P>Graphic Abstract</P><P>The geometry, spin density distribution and reactivity of radical adducts of stable <I>N</I>-heterocyclic carbenes, silylenes and germylenes demonstrate a strong dependence on the nature of the heterocycle and on the central atom. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c0sc00143k'> </P>

      • KCI등재

        Tracing the lactate shuttle to the mitochondrial reticulum

        Brooks George A.,Curl Casey C.,Leija Robert G.,Osmond Adam D.,Duong Justin J.,Arevalo Jose A. 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

        Isotope tracer infusion studies employing lactate, glucose, glycerol, and fatty acid isotope tracers were central to the deduction and demonstration of the Lactate Shuttle at the whole-body level. In concert with the ability to perform tissue metabolite concentration measurements, as well as determinations of unidirectional and net metabolite exchanges by means of arterial–venous difference (a-v) and blood flow measurements across tissue beds including skeletal muscle, the heart and the brain, lactate shuttling within organs and tissues was made evident. From an extensive body of work on men and women, resting or exercising, before or after endurance training, at sea level or high altitude, we now know that Organ–Organ, Cell–Cell, and Intracellular Lactate Shuttles operate continuously. By means of lactate shuttling, fuel-energy substrates can be exchanged between producer (driver) cells, such as those in skeletal muscle, and consumer (recipient) cells, such as those in the brain, heart, muscle, liver and kidneys. Within tissues, lactate can be exchanged between white and red fibers within a muscle bed and between astrocytes and neurons in the brain. Within cells, lactate can be exchanged between the cytosol and mitochondria and between the cytosol and peroxisomes. Lactate shuttling between driver and recipient cells depends on concentration gradients created by the mitochondrial respiratory apparatus in recipient cells for oxidative disposal of lactate.

      • KCI등재

        Health Effects of Underground Workspaces cohort: study design and baseline characteristics

        Gerard Dunleavy,Thirunavukkarasu Sathish,Nuraini Nazeha,Michael Soljak,Nanthini Visvalingam,Ram Bajpai,Hui Shan Yap,Adam C. Roberts,Thuan Quoc Thach,André Comiran Tonon,Chee Kiong Soh,Georgios Christo 한국역학회 2019 Epidemiology and Health Vol.41 No.-

        The development of underground workspaces is a strategic effort towards healthy urban growth in cities with ever-increasing land scarcity. Despite the growth in underground workspaces, there is limited information regarding the impact of this environment on workers’ health. The Health Effects of Underground Workspaces (HEUW) study is a cohort study that was set up to examine the health effects of working in underground workspaces. In this paper, we describe the rationale for the study, study design, data collection, and baseline characteristics of participants. The HEUW study recruited 464 participants at baseline, of whom 424 (91.4%) were followed-up at 3 months and 334 (72.0%) at 12 months from baseline. We used standardized and validated questionnaires to collect information on socio-demographic and lifestyle characteristics, medical history, family history of chronic diseases, sleep quality, health-related quality of life, chronotype, psychological distress, occupational factors, and comfort levels with indoor environmental quality parameters. Clinical and anthropometric parameters including blood pressure, spirometry, height, weight, and waist and hip circumference were also measured. Biochemical tests of participants’ blood and urine samples were conducted to measure levels of glucose, lipids, and melatonin. We also conducted objective measurements of individuals’ workplace environment, assessing air quality, light intensity, temperature, thermal comfort, and bacterial and fungal counts. The findings this study will help to identify modifiable lifestyle and environmental parameters that are negatively affecting workers’ health. The findings may be used to guide the development of more health-promoting workspaces that attempt to negate any potential deleterious health effects from working in underground workspaces.

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