Дисертації з теми "Biochemical Science"
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Drawert, Brian J. "Spatial Stochastic Simulation of Biochemical Systems." Thesis, University of California, Santa Barbara, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=3559784.
Повний текст джерелаRecent advances in biology have shown that proteins and genes often interact probabilistically. The resulting effects that arise from these stochastic dynamics differ significantly than traditional deterministic formulations, and have biologically significant ramifications. This has led to the development of computational models of the discrete stochastic biochemical pathways found in living organisms. These include spatial stochastic models, where the physical extent of the domain plays an important role; analogous to traditional partial differential equations.
Simulation of spatial stochastic models is a computationally intensive task. We have developed a new algorithm, the Diffusive Finite State Projection (DFSP) method for the efficient and accurate simulation of stochastic spatially inhomogeneous biochemical systems. DFSP makes use of a novel formulation of Finite State Projection (FSP) to simulate diffusion, while reactions are handled by the Stochastic Simulation Algorithm (SSA). Further, we adapt DFSP to three dimensional, unstructured, tetrahedral meshes in inclusion in the mature and widely usable systems biology modeling software URDME, enabling simulation of the complex geometries found in biological systems. Additionally, we extend DFSP with adaptive error control and a highly efficient parallel implementation for the graphics processing units (GPU).
In an effort to understand biological processes that exhibit stochastic dynamics, we have developed a spatial stochastic model of cellular polarization. Specifically we investigate the ability of yeast cells to sense a spatial gradient of mating pheromone and respond by forming a projection in the direction of the mating partner. Our results demonstrates that higher levels of stochastic noise results in increased robustness, giving support to a cellular model where noise and spatial heterogeneity combine to achieve robust biological function. This also highlights the importance of spatial stochastic modeling to reproduce experimental observations.
Barb, Jessica Gaus. "Biochemical, Genetic, and Cytogenetic Studies of Stokesia laevis (Stokes Aster)." NCSU, 2007. http://www.lib.ncsu.edu/theses/available/etd-11302007-145604/.
Повний текст джерелаEdwards, Lorraine Katy. "Biochemical characterization of mammalian high mobility group protein A2." FIU Digital Commons, 2006. http://digitalcommons.fiu.edu/etd/3118.
Повний текст джерелаMistry, Dharmit. "Mechanistic studies of some chemical and biochemical reactions." Thesis, University of Huddersfield, 2014. http://eprints.hud.ac.uk/id/eprint/23444/.
Повний текст джерелаHart, Jaynee E. "Biochemical and genetic approaches to modulate phototropin photoreceptor sensitivity." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30991/.
Повний текст джерелаThis lays the groundwork for extending the increased sensitivity observed in response to pulses in the photocycle mutants to responses other phot1-mediated responses, and for integrating new models of suppression of phot1 activity into our framework for phot1 activation and signaling.
Khartabil, Rana. "User-centered design and evaluation of a dynamic biochemical pathway visualization tool." Thesis, University of Ottawa (Canada), 2005. http://hdl.handle.net/10393/26944.
Повний текст джерелаWoo, Sung Sik Ph D. Massachusetts Institute of Technology. "Fast simulation of stochastic biochemical reaction networks on cytomorphic chips." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/107292.
Повний текст джерелаThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 169-181).
The large-scale simulation of biochemical reaction networks in cells is important in pathway discovery in medicine, in analyzing complex cell function in systems biology, and in the design of synthetic biological circuits in living cells. However, cells can undergo many trillions of reactions over just an hour with multi-scale interacting feedback loops that manifest complex dynamics; their pathways exhibit non-modular behavior or loading; they exhibit high levels of stochasticity (noise) that require ex- pensive Gillespie algorithms and random-number generation for accurate simulations; and, they routinely operate with nonlinear statics and dynamics. Hence, such simulations are extremely computationally intensive and have remained an important bottleneck in computational biology over decades. By exploiting common mathematical laws between electronics and chemistry, this thesis demonstrates that digitally programmable analog integrated-circuit 'cytomorphic' chips can efficiently run stochastic simulations of complex molecular reaction networks in cells. In a proof-of-concept demonstration, we show that 0.35 [mu]m BiC- MOS cytomorphic gene and protein chips that interact via molecular data packets with FPGAs (Field Programmable Gate Arrays) to simulate networks involving up to 1,400 biochemical reactions can achieve a 700x speedup over COPASI, an efficient bio- chemical network simulator. They can also achieve a 30,000x speedup over MATLAB. The cytomorphic chips operate over five orders of magnitude of input concentration; they enable low-copy-number stochastic simulations by amplifying analog thermal noise that is consistent with Gillespie simulations; they represent non-modular load- ing effects and complex dynamics; and, they simulate zeroth, first, and second-order linear and nonlinear gene-protein networks with arbitrary parameters and network connectivity that can be flexibly digitally programmed. We demonstrate successful stochastic simulation of a p53 cancer pathway and glycolytic oscillations that are consistent with results obtained from conventional digital computer simulations, which are based on experimental data. We show that unlike conventional digital solutions, an increase in network scale or molecular population size does not compromise the simulation speed and accuracy of our completely parallel cytomorphic system. Thus, commonly used circuit improvements to future chips in our digital-to-analog converters, noise generators, and biasing circuits can enable further orders of magnitude of speedup, estimated to be a million fold for large-scale networks.
by Sung Sik Woo.
Ph. D.
Pérez, Verona Isabel Cristina. "Approaches for the exact reduction of large-scale biochemical models." Thesis, IMT Alti Studi Lucca, 2020. http://e-theses.imtlucca.it/303/1/P%C3%A9rezVerona_phdthesis.pdf.
Повний текст джерелаSantra, Tapesh. "Evolutionarily stable and fragile modules of yeast biochemical network." Thesis, University of Glasgow, 2011. http://theses.gla.ac.uk/2644/.
Повний текст джерелаRoyle, Christopher. "Physiological and biochemical responses to frequent milking in dairy cows." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385209.
Повний текст джерелаIrvine, Darrell J. (Darrell John) 1973. "Spatially controlled presentation of biochemical ligands on biomaterial surfaces using comb polymers." Thesis, Massachusetts Institute of Technology, 2000. http://hdl.handle.net/1721.1/109636.
Повний текст джерелаVita.
Includes bibliographical references (p. 243-257).
by Darrell J. Irvine.
Ph.D.
Widdowson, Philip. "Biochemical and biophysical characterisation of Anopheles gambiae NADPH-cytochrome P450 reductase." Thesis, University of Liverpool, 2010. http://livrepository.liverpool.ac.uk/1496/.
Повний текст джерелаHocking, Damien. "Object-oriented simulation of chemical and biochemical processes /." Title page and contents only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phh6847.pdf.
Повний текст джерелаKlejnot, Marta. "Structural and biochemical insights into members of the kinesin and ubiquitin ligase families." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/5108/.
Повний текст джерелаMayer, Matthias. "A structural and biochemical comparison of wild-type and recombinant propanediol utilising bacterial microcompartments." Thesis, University of Kent, 2016. https://kar.kent.ac.uk/54756/.
Повний текст джерелаLaine, Marjo L. "Functional, biochemical and structural analyses of Plasmodium falciparum pyruvate dehydrogenase complex." Thesis, University of Glasgow, 2014. http://theses.gla.ac.uk/5043/.
Повний текст джерелаBray, James William. "Quantification of training load, neuromuscular fatigue, biochemical and endocrine responses to fast bowling in cricket." Thesis, University of Hull, 2017. http://hydra.hull.ac.uk/resources/hull:16447.
Повний текст джерелаLiu, Weizhi. "Microcapsule internalization by cells in vitro caused by physical and biochemical stimuli." Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8551.
Повний текст джерелаSINGH, SHERJANG. "ELECTROCHEMICAL PROPERTIES OF SiC-C MICROELECTRODE SYSTEM FOR NEURONAL AND BIOCHEMICAL SENSING." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1123783498.
Повний текст джерелаRiaz, Muhammad Qasim. "Influence of Biochemical Environments on Surface Fatigue of Additive Manufactured Ti-6Al-4V." Youngstown State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1485534165584066.
Повний текст джерелаVadrevu, Suryakiran. "Biochemical investigation of phosphodiesterase type IV post-translational modification, cellular localisation and interaction with associated binding proteins." Thesis, University of Glasgow, 2008. http://theses.gla.ac.uk/219/.
Повний текст джерелаGeldenhuys, Greta. "Egyptian goose (Alopochen aegyptiacus) : sensory, biochemical and physical meat quality as affected by gender, diet and ageing." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/95871.
Повний текст джерелаENGLISH ABSTRACT: In Southern Africa, the hunting of wildfowl species has increased considerably in the past few years. Crop farmers incur major financial losses due to the feeding activities of Egyptian geese (Alopochen aegyptiacus); consequently a large number of geese are hunted in an attempt to reduce the damage caused. With the current absence of scientific information baseline research investigating the meat quality of this species is essential. The sensory profile of Egyptian goose meat was found to be very distinct in relation to the characteristics of other well-known fowl species. It has very strong game aroma and flavour attributes with a prominent metallic aftertaste. The intense aroma and flavour notes were linked to the substantially higher iron content, as well as the high overall polyunsaturated fatty acid content as revealed by chemical profiling. The trained sensory panel also found the meat to be very tough (high shear force) compared to the other species. To identify the factors which may affect the overall consistency of the meat quality, the influence of three main effects namely; season (grain vs. non-grain diet), gender and portion was investigated. This revealed that season had the largest effect and harvesting periods should therefore be considered. The main issue is the higher intramuscular fat (IMF) content in winter (July), as well as the substantial difference in the fatty acid profiles of the two seasons. The forage vs. grain based diets during certain periods of the year leads to variation in the content of key fatty acids in the meat i.e. oleic acid, linoleic acid and α-linolenic acid. In winter, the meat had a characteristic, prominent game and metallic aroma while the summer (November) profile was governed by “sweet-oily-duck” and beef-like sensory notes. The fatty acid differences also result in variation between the omega 6 to omega 3 ratios of the seasons; the portions from winter are within the recommendations (ratio<5) and those from summer not. Regarding gender, the females had a lower carcass yield but higher IMF content. The female breast portion was also more tender (lower shear force). In attempting to elucidate the toughness of the meat, possible causes have been proposed. The pH decline in the pectoralis muscle occurs quite rapidly and it is possible that the high rigor temperature (>20 °C) may contribute to the increased toughness. Regardless of the proteolytic enzyme activity during the rigor period, the meat is still tough at 36 h post mortem and the proteolytic contribution may be overshadowed by the background toughness, i.e. the connective tissue content and fibre structure. The latter was confirmed when the breast portions were aged for 14 days and no change (decline) in the shear force values was observed even though myofibrillar degradation did occur (during ageing). Given the lack of a decline in the shear force, the aging of Egyptian goose meat as a means of improving the overall toughness cannot be proposed without further research. The study in its entirety provides substantial proof that the commercial utilisation of Egyptian goose meat is feasible.
AFRIKAANSE OPSOMMING: Die jag van wildsvoël spesies in Suider-Afrika het aansienlik toegeneem in die laaste paar jaar. Graanboere lei jaarliks groot finansiële verliese as gevolg van die voedingsgedrag van kolganse (Alopochen aegyptiacus). Gevolglik word ‘n groot hoeveelheid ganse elke jaar geoes om sodoende die skade te verminder. Met die huidige tekort aan wetenskaplike inligting is grondslag navorsing rakende die vleiskwaliteit van hierdie wildsvoël spesie noodsaaklik. Die sensoriese profiel van kolgansvleis is baie uniek in vergelyking met die vleis van ander bekende voël spesies. Dit word gekenmerk deur die sterk wildagtige aroma en geur tesame met ‘n baie prominente metaal nasmaak. Hierdie intense aroma en geur hou verband met ‘n baie hoër yster-inhoud, asook ‘n hoë poli-onversadigde vetsuur profiel soos uitgewys deur die chemiese karakteriserings studie. Die opgeleide sensoriese proepaneel het ook die vleis van hierdie voël spesie beskou as baie taai in vergelyking met die vleis van ander spesies. Ten einde te bepaal watter faktore die algehele variasie in vleiskwaliteit sal beïnvloed, is drie hoofeffekte naamlik, seisoen (graan teenoor nie-graan dieet), geslag en porsie ondersoek. Die verskeie studies het uitgewys dat seisoen die grootste invloed het en daarom sal die periodes waarin ganse geoes word in ag geneem moet word. Die hoër intramuskulêre vetinhoud in winter (Julie), asook die aansienlike verskil in die vetsuur profiele van die twee seisoene is die vernaamste verskille. Die weiding (hoofsaaklik gras) teenoor graan diëte wat gevolg word in sekere dele van die jaar lei tot variasie in die inhoud van belangrike vetsure (oliensuur, linoleïensuur en α-linoleensuur) in die vleis. In die winter het die vleis die kenmerkende en prominente wild geur en metaalagtige nasmaak getoon terwyl die profiel in die somer (November) hoofsaaklik bestaan het uit “soet-olierige-eend” en beesvleis geure. Die vetsuur verskille lei ook tot ‘n verskil in die omega-6 tot omega-3 verhouding van die seisoene; in die winter is die porsies binne die aanbevole voedingsvereistes (<5) terwyl die somer porsies nie aan hierdie vereistes voldoen het nie. Rakende die invloed van geslag, het die vroulike voëls ‘n laer karkas massa getoon tesame met ‘n laer intramuskulêre vetinhoud. Die borsie van die vroulike kolganse was ook sagter. In ‘n poging om die taaiheid van kolgansvleis te verklaar, is ‘n paar moontlike oorsake voorgestel. Die na-doodse pH daling in die borsspier vind redelik snel plaas, daarbenewens is dit ook moontlik dat die hoë temperature (>20 °C) waartydens rigor mortis plaasvind, kan bydrae tot die taaiheid. Ongeag die werking van die proteolitiese ensieme tydens die rigor periode was die vleis steeds taai 36 uur na dood, daarom was die proteolitiese bydrae moontlik oorskadu deur die agtergrond-taaiheid, dit wil sê die bindweefsel inhoud en vesel struktuur. Laasgenoemde is bevestig toe die borsspiere verouder is vir ‘n tydperk van 14 dae. Geen verandering (afname) in die instrumentele taaiheid is waargeneem nie, selfs al het miofibrillêre afbraak plaasgevind. Aangesien daar geen afname in instrumentele taaiheid opgemerk is nie kan veroudering van kolgansvleis, met die doel om die taaiheid te verbeter, nie aanbeveel word voor verdere navorsing nie. In geheel voorsien hierdie studie beduidende motivering rakende die moontlike kommersiële aanwending van kolgansvleis.
Young, David. "Spectroscopic, structural, mutational and biochemical characterisation of quinol-dependent nitric oxide reductase of Neisseria meningitidis." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2034441/.
Повний текст джерелаDyer, Scott Douglas. "Evaluation of the efficacy of the stress protein response as a biochemical water quality biomonitoring method." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc798352/.
Повний текст джерелаVandongen, Robert. "[Biochemical and epidemiological basis of hypertension] : published works submitted to the University of Adelaide for the degree of Doctor of Science /." Title page and summary only, 1987. http://web4.library.adelaide.edu.au/theses/09SD/09sdv246.pdf.
Повний текст джерелаBaeza, Rita. "Comparison of technologies to control the physiological, biochemical and nutritional changes of fresh cut fruit." Manhattan, Kan. : Kansas State University, 2007. http://hdl.handle.net/2097/494.
Повний текст джерелаLauer, Nathan T. "Physiological and Biochemical Responses of Bald Cypress to Salt Stress." UNF Digital Commons, 2013. http://digitalcommons.unf.edu/etd/454.
Повний текст джерелаChangsawang, Narin. "The effects of growth conditions on the elemental and biochemical composition of the diatom Thalassiosira weissflogii and the haptophyte Emiliania huxleyi." Thesis, University of Essex, 2015. http://repository.essex.ac.uk/15697/.
Повний текст джерелаAl, Mohamad Zakriya Ali E. "Quantitative assessment of the biochemical composition of equine cartilage using 7T ultra-high field magnetic resonance imaging (MRI) techniques." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/8227/.
Повний текст джерелаMatchett, Ashley A. "Genetic and biochemical analysis of materials from a medieval population from Ynys Mon North Wales." Thesis, University of Central Lancashire, 2011. http://clok.uclan.ac.uk/3880/.
Повний текст джерелаChou, Lan-Szu. "Isolation and Biochemical Characterization of Acid- and Bile- Tolerant Strains of Lactobacillus Acidophilus and Bifidobacterium Bifidum." DigitalCommons@USU, 1997. https://digitalcommons.usu.edu/etd/5427.
Повний текст джерелаHalling, Linder Cecilia. "Biochemical and functional properties of mammalian bone alkaline phosphatase isoforms during osteogenesis." Doctoral thesis, Linköpings universitet, Avdelningen för mikrobiologi och molekylär medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-127100.
Повний текст джерелаBolton, Shawna N. "Forensic taphonomy : investigating the post mortem biochemical properties of cartilage and fungal succession as potential forensic tools." Thesis, University of Wolverhampton, 2015. http://hdl.handle.net/2436/579577.
Повний текст джерелаBergendahl, Christina. "Development of competence in biochemical experimental work : Assessment of complex learning at university level." Doctoral thesis, Umeå : Dept. of Chemistry, Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-313.
Повний текст джерелаMartinenko, Evgeny. "Prediction of survival of early stages lung cancer patients based on ER beta cellular expressions and epidemiological data." Master's thesis, University of Central Florida, 2011. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4796.
Повний текст джерелаID: 030646185; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Thesis (M.S.)--University of Central Florida, 2011.; Includes bibliographical references (p. 32-33).
M.S.
Masters
Mathematics
Sciences
Mathematical Science
Ross, Trinette Noel. "Evaluation of bone biochemical markers and inflammatory markers in yearlings fed varying ratios of omega-6 and omega-3 polyunsaturated fatty acids." [College Station, Tex. : Texas A&M University, 2006. http://hdl.handle.net/1969.1/ETD-TAMU-1036.
Повний текст джерелаSchlipf, Daniel M. "BIOMOLECULE LOCALIZATION AND SURFACE ENGINEERING WITHIN SIZE TUNABLE NANOPOROUS SILICA PARTICLES." UKnowledge, 2015. http://uknowledge.uky.edu/cme_etds/44.
Повний текст джерелаGupta, Prachi. "SYNTHESIS AND CHARACTERIZATION OF ANTIOXIDANT CONJUGATED POLY(ΒETA-AMINO ESTER) MICRO/NANOGELS FOR THE SUPPRESSION OF OXIDATIVE STRESS". UKnowledge, 2016. http://uknowledge.uky.edu/cme_etds/58.
Повний текст джерелаLarsson, Birgitta. "Physiological Importance of 1,25(OH)2D3 Membrane-Initiated and Nuclear Actions in Chickens as a Function of Growth, and Maturation in Male and Female Chickens." DigitalCommons@USU, 2002. https://digitalcommons.usu.edu/etd/5500.
Повний текст джерелаJia, Yang. "FORMS OF SUPPLEMENTAL SELENIUM IN VITAMIN-MINERAL MIXES DIFFERENTIALLY AFFECT SEROLOGICAL AND HEPATIC PARAMETERS OF GROWING BEEF STEERS GRAZING ENDOPHYTE-INFECTED TALL FESCUE." UKnowledge, 2019. https://uknowledge.uky.edu/animalsci_etds/97.
Повний текст джерелаAhn-Jarvis, Jennfier H. "Development of a standardized functional soy product for cancer prevention trials:Phase II evaluation of isoflavone bioavailability in men with asymptomatic prostate cancer." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1357255127.
Повний текст джерелаLiu, Yunhao. "Structural and biochemical analysis of HutD from Pseudomonas fluorescens SBW25 : a thesis submitted in fulfilment of the requirements for the degree of Master of Science in Molecular Biosciences at Massey University, Auckland, New Zealand." Massey University, 2009. http://hdl.handle.net/10179/1074.
Повний текст джерелаTao, Jing. "Treatment of sanitary sewer overflow using fixed media bioreactors." Columbus, Ohio : Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1228071779.
Повний текст джерелаAuthimoolam, Sundar Prasanth. "BIOMIMETIC ORAL MUCIN FROM POLYMER MICELLE NETWORKS." UKnowledge, 2015. http://uknowledge.uky.edu/cme_etds/51.
Повний текст джерелаSims, Lynn. "Biochemical Studies of ABCE1." Doctoral diss., University of Central Florida, 2012. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/5501.
Повний текст джерелаPh.D.
Doctorate
Biology
Sciences
Biomedical Sciences
Djerdjouri, Nour-Eddine. "Hydrogen peroxide delignification in a biomimetic system based on manganese peroxidase." Diss., Available online, Georgia Institute of Technology, 2005, 2003. http://etd.gatech.edu/theses/available/ipstetd-1017/.
Повний текст джерелаThakkar, Jay. "Biochemical Evaluation of Lignin-like Molecules." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/199.
Повний текст джерелаZhou, Jin Chuan. "Biochemical characterisation of KDM2A." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:030faa1d-5d3c-4066-9e9f-a44cd13cf85c.
Повний текст джерелаSoda, Takahiro. "Converging biochemical pathways in psychiatric disorders." Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/73775.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references.
According to the World Health Organization, neuropsychiatric diseases account for approximately one third of years lost to disability. Yet, despite this huge disease burden, there is a lack of new treatments under development: approved treatments all essentially target the same target(s), if the target itself is known. There is now considerable evidence for a common set of heritable risk for psychiatric disorders including schizophrenia, bipolar disorder, as well as autism. Many of these risk alleles affect genes implicated in neuronal development with known roles at an early stage; these genes would have an effect on the individual before the onset of overt symptoms or diagnosis. Furthermore, many of the genes identified are known to participate in established pathways that are relevant for neuronal development and function. It is important then to address the causality between these signaling pathways that are important for neurodevelopment, and the risk of developing neuropsychiatric disorder. The work presented in this thesis represents two projects that aim to work toward this goal. The first project pertains to the mechanisms of transcriptional repression by DISC1 on ATF4-mediated gene transcription. The second project presents some initial steps towards uncovering the role of BCL9 in neuronal development.
by Takahiro Soda.
Ph.D.
Pooler, Amy Melissa. "Regulation of biochemical pathways involved in neurodegeneration." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/31177.
Повний текст джерелаIncludes bibliographical references.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. Although much is known about how AD affects the brain, the cause of this disease remains elusive. Current AD treatments target symptoms of the disease but do not prevent or slow the underlying neurodegeneration. Therefore, research into the biochemical mechanisms of AD is necessary in order to develop a better understanding of how to treat it. Misprocessing of the amyloid precursor protein (APP) in the brains of AD patients leads to accumulation of the amyloidogenic peptide AD. A soluble APP fragment (APPS) is formed when APP is cleaved within the AP region, thereby preventing AP formation. Activation of 5-HT2A or 5-HT2c receptors has been shown to increase APPS secretion in vitro; therefore, we determined whether activation of these receptors might have a similar effect in vivo. We found that a 5-HT2A/2c agonist affected brain APP metabolism in guinea pigs by increasing CSF levels of APPS and, following chronic treatment, by decreasing levels of AP. Our data indicate that activation of brain 5-HT2c receptors may be useful for treating AD by reducing AP production. Traumatic brain injury is a risk factor for AD, although the reason is unknown. To explore this relationship, we examined the effect of the inflammatory mediator PGE2 on production of APP in cultured microglia. We found that PGE2 treatment stimulated APP overexpression and that this effect was likely mediated by the prostaglandin EP2 receptor and the cAMP signaling cascade. Therefore, EP2 receptor antagonists may constitute an additional target for prevention of AD following brain injury.
(cont.) The neuropathology associated with AD includes neuritic dystrophy and degeneration. Therefore, restoration of neuritic growth and repair of phospolipid membranes may be important for treating AD. We found that treatment of NGF- differentiated PC 12 cells with the phospholipid precursor uridine enhanced neurite outgrowth by both enhancing phosphatide biosynthesis and by stimulating a G-protein receptor-coupled signaling pathway. Subsequently, we found that the HMG-CoA reductase inhibitor pravastatin enhanced neurite outgrowth in rat hippocampal neurons, not by affecting cholesterol synthesis, but by inhibition of isoprenoid formation. Stimulation of neurite growth by either uridine or statins may reduce AD risk by averting neuritic dystrophy and degeneration. However, further studies must be conducted to determine whether they are able to affect neuritic processes in vivo.
by Amy Melissa Pooler.
Ph.D.