Carotenoids are the precursor of several metabolites with regulatory functions, which include the plant hormones abscisic acid (ABA) and strigolactones (SLs), and signaling molecules, such as β-cyclocitral. These carotenoid-derivatives originate from oxidative breakdown of the double bond resulting in carbonyl cleavage-products designated as apocarotenoids. The cleavage reaction causing apocarotenoid formation is catalyzed frequently by Carotenoid Cleavage Dioxygenases (CCDs). Several lines of evidence indicate the presence of yet unidentified apocarotenoids with regulatory or signaling function. Here, we first characterized the biological functions of the apocarotenoid zaxinone formed by ZAXINONE SYNTHASE (ZAS), a member of an overlooked, widely distributed plant CCD clade. The loss-of-function rice zas mutant contains less zaxinone, exhibiting retarded growth with elevated levels of SLs that determines plant architecture, mediates mycorrhization, and facilitates the germination of root parasitic seeds, such as Striga spp. The zaxinone treatment rescued zas phenotypes, down-regulated SL biosynthesis and release, and enhanced root growth in the wild-type rice seedlings. Next, we performed multi-omics analysis demonstrating zaxinone increased sugar metabolism and induced photosynthesis in a manner that led to phenotypical changes in rice roots. Besides, transcriptome analysis showed that zaxinone upregulated CYTOKININ GLUCOSYLTRANSFERASES expression in roots, which might explain the increase in the apex and meristem length, and in the number of cellular layers. Finally, the investigation of zaxinone biology and the utilization of its application is constrained by its laborious organic synthesis and low abundance in natural sources. Therefore, we developed easy-to-synthesize and highly efficient Mimic of Zaxinone (MiZax), based on the structure-activity-relationship study using a series of apocarotenoids. Activity-based experiments unraveled MiZax3 and MiZax5 were at least as active as zaxinone in rescuing root phenotypes of the zas mutant, promoting root growth in wild-type seedlings, and reducing SL biosynthesis and release. Taken together, zaxinone is a key regulator of rice growth and development, which regulates sugar metabolism, suppresses SL biosynthesis, fine-tunes cytokinins level, and modulates biotic interactions with arbuscular mycorrhizal (AM) fungi. Our work also provides easy-to-synthesize mimics for illuminating zaxinone biology and as a tool to improve crop growth and reduce the infestation by Striga hermonthica, a severe threat to food security worldwide.

京都大学 / 新制・課程博士 / 博士(生命科学) / 甲第24270号 / 生博第484号 / 新制||生||64(附属図書館) / 京都大学大学院生命科学研究科統合生命科学専攻 / (主査)教授 野田 岳志, 教授 原田 浩, 教授 豊島 文子 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM

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Policies intended to pursue climate mitigation through soil carbon sequestration require accurate estimates of soil carbon stocks and projections of how carbon pools will change with future climate. In this study, the process model MIMICS-CN was utilized to explore the potential changes in bulk soil organic carbon (SOC) and protected mineral-associated organic matter (MAOM) with changes in mean annual temperature (MAT) and annual net primary productivity (NPP) for the native range of loblolly pine (Pinus taeda L). A Monte Carlo method was used to calibrate a large ensemble of model parameters using observational data from loblolly pine stands. Spatial projections of carbon pools across the native range of loblolly pine were produced for nine temperature and productivity scenarios representing a range of likely futures. The standard deviation of the mean total SOC pool to a depth of 30 cm was 3.6 kg C m-2 while the standard deviation of potential changes in pool magnitude was 0.96 kg C m-2. Associated with regional climate change projections, increases in MAT caused losses in bulk SOC but did not affect MAOM. Simulated increases in NPP resulted in increased bulk SOC, MAOM and the proportion of SOC that is MAOM (MAOM:SOC) highlighting the importance of productivity in sequestering atmospheric CO2 in general and in protected C pools, specifically. SOC pools did not change consistently across the landscape. Rather, they varied by subregion due to differences in soil texture and changes in forecasted NPP. Soils with clay contents above 18% had the greatest potential to accumulate MAOM and bulk SOC under a realistic future climate scenarios. In regions with low clay content, significant increases in total SOC are driven by the accumulation of C in unprotected SOC sub-pools. With the maximum likely increase in NPP (31.4%), a regionwide increase in total SOC of 29% was projected whereas subregions in which NPP decreases showed no potential to increase soil carbon stocks. We conclude that the management of loblolly pine to increase productivity can increase the amount of SOC and the residence time of bulk SOC over decadal time scales, however regional differences in the proportion of C in MAOM and unprotected pools must be considered when planning silvicultural management. / Master of Science / Managing soil carbon in southeastern U.S. loblolly pine forests creates a sustainable system of producing large quantities of forest products and has the potential to remove carbon dioxide from the atmosphere. Accurate estimates of the amount of carbon in soils at regional scales and projections of changes in soil carbon caused by global change are critical components to successfully determining the effectiveness of this approach to climate change mitigation. In this study, a model of soil carbon designed to describe the range of loblolly pine is utilized to simulate soil carbon changes using three realistic potential increases in temperature and three projections of changing ecosystem productivity to the year 2050. As temperature increases, the total amount of carbon in soils decreases because the rate of decomposition by microbial organisms hastens. However, with increasing productivity, losses of soil carbon due to increased temperatures are mitigated, and, at the highest levels of productivity, soil carbon stocks and the resistance of soil carbon to future losses increase by up to 26 percent. Here, we propose a productivity focused management approach to sequestering carbon in loblolly pine soils and highlight sub regions which may be more vulnerable to soil carbon losses due to environmental factors such as flooding and nutrient limitations.

Doctor of Philosophy / Department of Chemistry / Christer B. Aakeroy / A family of bis-pyridine based pharmaceutical active ingredients were synthesized and co-crystallized with four iodoperfluoroalkanes. Thirteen new crystal structures that are driven by I‧‧‧N(py) halogen bonds, are presented and compared with that of their hydrogen-bonded analogues. Halogen bonded co-crystals exhibit two different structural arrangements, as opposed to layered architectures observed in hydrogen bonded co-crystals. In order to explore the effect of aromatic stacking interactions on hydrogen and halogen bond driven co-crystallization process, we utilized a series of aromatic hydrogen and halogen bond donors in combination with bis-pyridine based pharmaceutical active ingredients. Aromatic stacking between the donor and the acceptor were limited, due to the lack of complementarity between the donor and the acceptor in terms of size, shape and geometry. In that case, homomeric interactions between the single components were translated into the structure of the binary co-crystals. According to our charge calculations, similarly activated hydrogen and iodine atoms possess similar electrostatics. Therefore, we wanted to investigate the interchangeability of hydrogen bonds and halogen bonds by utilizing 2-aminopyrimidine as the backbone for C(sp)-H and C(sp)-I functionalities which makes self-complementary ribbons via NH‧‧‧N synthons. Our results show that the ethynyl proton is capable of acting as a synthon mimic of ethynyl iodine by interchangeable C(sp)-H‧‧‧N hydrogen bonds and C(sp)-I‧‧‧N halogen bonds. We exploited the halogen bonding donor capability of iodo, bromo and chloro ethynyl functionalities towards a series of halide ions. Based on the grinding experiments these donors showed 90%, 70% and 50% success rates towards halides. Among the halides, chlorides exhibited the highest red shift compared to bromides and iodides. We synthesized a series of cavitands functionalized with hydrogen bond donor and acceptor groups and studied their binding preferences towards a series of active ingredients. We have shown that suitably functionalized cavitands can act as carriers of active ingredients and especially, selective binding of aspirin is demonstrated using a two-point binding mode.

Thesis (MScEng (Mechanical and Mechatronic Engineering))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: The c2 goodness-of-fit (GOF) test was used to determine which standard femoral component would achieve the best geometrical fit for a specific patient. This was done by creating 3D models from computerized tomography scan data through computer segmentation using Materialise MIMICS. The second step was to measure the morphological dimensions of the distal femur whereof twelve were selected and compared to the dimensions of two commercial femoral prosthesis designs. Thirdly, cadaveric femurs were scanned with a 3D desktop scanner to create a database with the dimensions of healthy knees. The 3D model database of the cadaveric femurs included cartilage layer. A cartilage thickness was added to the CT knee dimensions using a self-organizing map (SOM) calculation based on the healthy knee database. The developed method calculated alignment angles with higher accuracy than presently used and determined preoperatively which size to implant. Kinematic simulations of total knee arthroplasty (TKA) knees were compared to normal knee simulations created in LifeMOD. The articulating surface was the only variable changed between the two simulations and the kinematics of different sizes were evaluated. A method was created to scale the femoral component using the standard available sizes. The completed project will be used as foundation for customization of TKA prostheses. / AFRIKAANSE OPSOMMING: Die c2 graad van passing toets metode was gebruik om te bereken watter standaard femorale komponent ’n patiënt die beste geometries pas. Dit was gedoen deur eerstens 3D modelle gemaak vanaf CT skandeer data deur rekenaar segmentasie met Materialise MIMICS. Daarna was morfologiese dimensies gemeet vanaf die distale femur, waarvan twaalf gekies en vergelyk was teen two kommersiële femorale prostesis ontwerpe. Laastens was kadawer femurs geskandeer met ‘n 3D skandeerder om ’n databasis van gesonde knieë te maak. Die 3D modelle van die kadawer bene het die kraakbeen laag bevat. Die kraakbeen dikte was by die CT knie dimensies gevoeg d.m.v. SOM en die gesonde knie databasis. Die nuwe metode bereken die belynings hoeke met hoër akkuraatheid as wat huidiglik gebruik word en bereken voor die operasie watter grote om te gebruik. Kinematiese simulasies van knie prostesis was vergelyk met ’n normale knie simulasies gemaak in LifeMOD. Die artikulêre oppervlakte was die enigste veranderlike tussen die twee simulasies en kinematika van verskillende grotes was ondersoek. ‘n Metode was geskep om die standaard femorale komponent se skaal te verander vir ’n beter passing.

Recently some chemicals has been accused of mimicking the female hormone estrogen. The mode of action is termed estrogen-mimicking, because of the effects that is produced by these chemicals. Playing canary in a coal mine, wildlife was the first to indicate that something was wrong. Reproductive abnormalities such as abnormal sperm, reduced sperm production, cryptorchidism (undescended testes). abnormal hormone levels – particularly high estrogen ratios to that of testosterone. infertility, and genital abnormalities were all evidence that something in the environment was affecting the reproductive status of these animals. Also in humans instances like rising cases of infertility, abnormal sperm conditions and cases of breast cancer raised an increased concern about the potential disruptive effects of these substances on the human existence. After investigations were conducted, it was found that substances which enhance the quality of life like some detergents, agricultural products, additives to plastic, dyestuffs, paint components and pharmaceuticals to name but a few, all caused an abnormal reproductive status as seen in animals. The aims of this study were not to focus on the effect of these substances, but rather to identify estrogen and estrogen - mimics in the South African environment and to evaluate their presence in the water environment qualitatively and quantitatively with the most suitable analytical methods. Estrogen - mimics such as nonylphenol. o'p' and p'p' DDE, o'p' DDD, lindane, atrazine and the PCB's : Arochlor 1254 & Arochlor 1260 were found to contaminate the environment. The drinking water tested of the PWV area indicated that the water was free of these substances, and thus indicated a present safe situation. / Thesis (MSc (Farmaseutika))--PU for CHE, 1998

Ces travaux de thèse s'inscrivent dans un projet à long terme visant à développer de nouveaux outils nécessaires à l'élucidation de mécanismes biologiques impliquant des interactions de type protéine-protéine mettant en jeu des structures secondaires protéiques de type polyproline II (PPII). En particulier, nous nous sommes intéressés à la conception, synthèse et valorisation de spirolactames originaux capables de mimer une hélice PPII, point de départ dans la recherche de nouvelles molécules d'intérêts thérapeutiques. Cette structure secondaire unique, caractéristique des ligands SH3, joue un rôle essentiel dans certaines activités biologiques telles que les phénomènes de reconnaissance, la transduction de signal, la transcription, la mobilité cellulaire, les réponses immunitaires et se trouve aussi impliquée dans des pathologies majeures telles que le SIDA, la Maladie d'Alzheimer et plusieurs tumeurs cancéreuses. Face à l'importance des structures secondaires PPII dans des cibles d'intérêt thérapeutique, dans les phénomènes de reconnaissance protéine-protéine, et face à l'absence dans la littérature de mimes PPII pertinents, ces travaux se sont attachés à l'élaboration et la valorisation d'outils PPII contraints, stables vis-à-vis de la dégradation protéasique. Ils nous ont tout d'abord permis de développer un accès stéréocontrôlé à une plateforme spiro [4,4] inédite, en nous appuyant sur une réaction de contraction de cycle développée récemment dans notre groupe, le réarrangement transannulaire de lactames activés (TRAL). Les études de dynamique moléculaire, et de dichroïsme circulaire nous ont permis de démontrer que certains des composés spiro synthétisés adoptent une structure "PPII-like", d'autres semblent au contraire se structurer en coude bêta. / This work is part of a long term project with the aim to develop new tools for the elucidation of biological mechanisms involving protein-protein interactions with the participation of the protein secondary structure named polyproline type II (PPII). In particular, we are interested in the design, the synthesis and the development of original spirolactams as first mimics of PPII helix, the starting point in the discovery of new compounds of therapeutic interest. This unique secondary structure, characteristic of SH3 ligands, plays a critical role in various biological activities such as the phenomena of recognition, signal transduction, transcription, cell motility, immune responses and is also involved in major diseases such as AIDS, Alzheimer's disease and several carcinogenic tumors. Regarding the importance of the PPII secondary structures in targets of therapeutic interest and in the phenomena of protein-protein recognition, and observing the absence in the literature relevant PPII mimics, this thesis have focused on the development of constrained PPII tools, stable versus protease degradation. This work first allowed us to develop an stereocontroled access to a novel spiro [4.4] scaffold, relying on a new ring contraction reaction recently developed in our group, namely transannular rearrangement of activated lactams (TRAL) . Studies of molecular dynamics, and circular dichroism have demonstrated that some of the synthesized spiro compounds adopt a "PPII-like" structure, others seems to be structured in beta-turn.

<p>Ostvarene su vi&scaron;efazne stereospecifične sinteze tiazolnih C-nukleozida, novih analoga, odnosno mimetika tiazofurina polazeći iz D-glukoze i D-ksiloze. Ispitana je <em>in vitro </em>citotoksična aktivnost sintetizovanih C-nukleozida prema odabranim humanim tumorskim ćelijskim linijama (K562, HL 60, Jurkat, Raji, PC 3, HT-29, MCF-7, MDA-MB-231, HeLa i Hs 294T) kao i prema ćelijama normalnih fetalnih fibroblasta pluća (MRC-5).</p> / <p>Multiphase stereospecific synthesis of thiazole C-nucleosides, new analogues and mimics of tiazofurin,&nbsp;has been achives starting from D-glucose and D-xylose.&nbsp;<br />We examined the in vitrocytotoxic activity of&nbsp;synthesized C-nucleosides by selected human tumor cell&nbsp;lines (K562, HL 60, Jurkat, Raji, PC 3, HT-29, MCF-7,&nbsp;<br />MDA-MB-231, HeLa and Hs 294T) and the cells of&nbsp;normal fetal lung fibroblasts (MRC-5).</p>