Linking microtubules to the activation of CDC42 in fission yeast

Cell polarity is an essential property of most cell types and relies on a dynamic cytoskeleton of actin filaments and microtubules. In rod-shaped S. pombe cells microtubules are organized along the length of the cell and transport polarity factors to cell tips to regulate cell polarity. An important cell polarity factor is the protein Tea4, which is responsible for correct cell morphogenesis and bipolar growth. During my research I confirmed the known transport mechanism of Tea4 and I also showed alternative localization and anchoring mechanisms at the cell ends. Tea4 contains a conserved SH3 domain, the function of which was unknown and my results show that the SH3 domain of Tea4 is essential for Tea4 function in vivo. First, cells with tea4SH3 mutations show aberrant cell shapes and monopolar growth patterns similar to tea4A and in addition SH3 domain is important for proper localization of multiple cell polarity proteins. Second, I showed that Tea4 associates with Type 1 Phosphatase Dis2 through both its SH3 domain and an RVxF motif. Tea4 also binds the DYRK kinase Pomi through its SH3 domain. In addition Tea4 is proposed to promote the local dephosphorylation of Pomi by Dis2 to induce the formation of a cortical gradient from cell ends essential for cell size homeostasis. Polarized growth is also controlled by cell tip-localized Cdc42. This Rho- family GTPase is activated by the Guanine Exchange Factors Gef1 and Scd1 and inactivated by the Rho GTPase Activating Protein Rga4. In this study, I investigated the mechanisms of how Tea4 promotes Cdc42 activation. My work suggests that Tea4 promotes the local exclusion of Rga4, which in turn allows the accumulation of active Cdc42, which may result in growth. Exclusion of Rga4 by Tea4 is likely to be mediated by Dis2-dependent dephosphorylation. These results suggest a molecular pathway that links the microtubule- associated factor Tea4 with Cdc42 to promote cell polarization and morphogenesis. - La polarité cellulaire est une propriété essentielle de la plupart des types cellulaires et s'appuie sur une dynamique des cytosquelettes d'actine et de microtubules. Dans les cellules en forme de bâtonnet de S. pombe les microtubules sont alignés selon l'axe longitudinal de la cellule et les facteurs de polarité transportés aux extrémité cellulaires afin de réguler la polarité cellulaire. Un facteur important de polarité cellulaire est la protéine Tea4, qui est responsable de la morphogenèse des cellules et leur croissance bipolaire. Au cours de mes recherches, j'ai confirmé les mécanismes connus de transport de Tea4 et j'ai aussi mis en évidence d'autres mechanismes de localisation et d'ancrage de Tea4 aux extrémités cellulaires. Tea4 contient un domaine SH3 conservé, dont la fonction était inconnue et mes résultats montrent que le domaine SH3 est essentiel pour la fonction de Tea4 in vivo. Tout d'abord, les cellules avec des mutations tea4sm ont des formes aberrantes et leur croissance est monopolaire de manière similaire au mutant tea4A. De plus ce domaine SH3 est important pour la localisation correcte de plusieurs protéines de polarité cellulaire. Deuxièmement, j'ai montré que Tea4 s'associe avec la Phosphatase de Type-1 Dis2 par son domaine SH3 et un motif RVxF. Tea4 se lie également la kinase DYRK Pomi par son domaine SH3. De plus, Tea4 pourrait favoriser la déphosphorylation locale de Pomi par Dis2 afin d'induire la formation d'un gradient cortical de Pomi essentiel pour l'homéostasie de la longueur des cellules. La croissance polarisée est également contrôlée par la protéine Cdc42 localisée aux extrémités cellulaires. Cette GTPase de la famille de Rho GTPase est activée par les facteurs échange de guanine Gef1 et Scd1 et inactivée par la protéine "Rho GTPase activating" Rga4. Dans cette étude, j'ai étudié les mécanismes d' activation de Cdc42 par Tea4. Mes résultats suggèrent que Tea4 favorise l'exclusion locale de Rga4, ce qui permet l'accumulation de Cdc42 active, nécessaire à la croissance. L' exclusion de Rga4 par Tea4 est vraisemblablement médiée par une déphosphorylation Dis2- dépendente. Ces résultats suggèrent une voie moléculaire qui lie le facteur associé aux microtubules Tea4 à Cdc42 pour promouvoir la polarisation cellulaire et la morphogenèse. - Cell polarity is important for several essential biological functions such as generation of distinct cell fates during development and function of differentiated cells. Defective cell polarity has been related to uncontrolled cell division and subsequently to cancer initiation. Cell polarity depends on a functional cytoskeleton that consists of actin filaments and microtubules, which maintains cell shape, helps cellular motion, enables intracellular protein transport and plays a vital role in cell division. A component of cytoskeleton is microtubules that regulate cell polarization in diverse cell types. During my research, I worked with Schizosaccharomyces pombe, also named fission yeast, a powerful unicellular model organism that allows combination of genetic, biochemical and microscopic analysis for the proper study of cell polarity. Microtubule-associated protein Tea4 is transported to cell tips where it is thought to organize polarized growth. I showed that Tea4 and its evolutionarily conserved SH3 domain play an important role for maintenance of fission yeast cells shape and growth. Furthermore, Tea4 is responsible for the proper localization of multiple polarity proteins and acts as a mediator to control the local activity of an essential polarity regulator called Cdc42. Thus, my results provide a better understanding of the molecular mechanisms that regulate cell polarity. - La polarité cellulaire est importante pour plusieurs fonctions biologiques essentielles telles que la différenciation cellulaires au cours du développement et de la fonction de cellules différenciées. Les défauts de la polarité cellulaire ont été liés à des divisions cellulaires incontrôlées et à l'initiation de tumeur. La polarité cellulaire dépend d'un cytosquelette fonctionnel, qui maintient la forme des cellules, aide à la migration cellulaire, permet le transport intracellulaire des protéines et joue un rôle essentiel dans la division cellulaire. Un composant du cytosquelette est constitué de microtubules qui régissent la polarisation cellulaire dans divers types cellulaires. Au cours de mes recherches, j'ai travaillé avec Schizosaccharomyces pombe, appelé également levure fissipare, un modèle unicellulare puissant qui permet la combinaison de différentes d'approches expérimentales: génétiques, biochimiques et microscopiques pour l'étude de la polarité cellulaire. La protéine Tea4 associée aux microtubules est transportée aux extrémités cellulaires où elle organise la croissance polarisée. J'ai montré que Tea4 et son domaine conservé SH3 jouent un rôle important pour le maintien de la forme des cellules de levure et leur croissance. De plus, Tea4 est responsable de la localisation correcte de multiples facteurs de polarité et agit comme un médiateur pour contrôler l'activité locale d'un régulateur de polarité essentiel appelé Cdc42. Ainsi, mes résultats permettent de mieux comprendre les mécanismes moléculaires qui régulent la polarité cellulaire.

Consumer Advisory Bulletin, Credit Cards vs. Nailing Down Home Repair Rip-Offs & Disputes, April 2011

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Consumer Advisory Bulletin, ID Theft: Prevent & Protect, May 2011

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Utilization of Boron (10B) derived from fertilizer by sugar cane

The response to B in agricultural systems of sugar cane is still an unexplored issue; B application has however recently been widely publicized and used with a certain degree of frequency. The use of 10B-labeled fertilizers may further contribute to clarify this practice. With the objective of evaluating sugar cane use of B (10B) derived from fertilizer (boric acid), an experiment was conducted under field conditions in the 2005/2006 growing season. The experiment consisted of the installation of microplots (2 x 1.5 m) where 4 kg ha-1 B (boric acid with 85.95 % in 10B atoms) dissolved in water was applied 90 days after planting (May 2005). The solution was applied to the soil on both sides of the plant row at a distance of 20 cm. After harvest (June 2006) the B content and 10B abundance in % atoms in all parts of the sugar cane plants (stalks, dry leaves, tips and roots) were determined. Results showed that the total B accumulated was 471 g ha-1 in the entire plant (35 % in the stalks, 22 % in the dry leaves, 9 % in the tips and 34 % in the roots). The sugar cane plants used on average 14 % of the total accumulated B in the above-ground part (44 g ha-1) and 11 % in the roots (19 g ha-1), totaling 13 % in the entire plant (63 g ha-1). The recovery of 10B-fertilizer by sugar cane plants was low, around 2 % of the total applied amount.

Consumer Advisory Bulletin, Door-to-Door Sales: Your Right to Cancel, June 2011

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Consumer Advisory Bulletin, Be Wary of Online Payday Loans, July 2011

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Orchid growth and nutrition in response to mineral and organic fertilizers

Orchid fertilization is fundamental for a satisfactory plant growth and development for commercial orchid production as well as in collections. Mineral and/or organic sources can be used for fertilization. The objective of this study was to evaluate the effect of the use of organic and/or mineral fertilizers on the nutrition and growth of orchid (Laelia purpurata 'werkhanserii' x L. lobata 'Jeni') seedlings in greenhouse. The following fertilizers were tested: an NPK fertilizer + micronutrients; a Ca source in the form of calcium nitrate; two organic fertilizers, one prepared with a mixture of bone meal, castor meal and ash, and a similar commercial fertilizer. The organic fertilizers were distributed on the surface of the pots every two months and the minerals were applied weekly to the substrate in 25 mL aliquots of a solution containing 1 g L-1 of the respective fertilizer. The plant response to the application of mineral together with organic fertilizer was better, with higher dry matter production than by the isolated application of each fertilizer (organic or mineral). The treatments with calcium nitrate + NPK fertilizer did not differ significantly from the use of NPK fertilizer, probably due to the S deficiency detected in a mineral analysis of the tissues. Commercial organic fertilizer had a very elevated B level, leading to toxicity symptoms, reduced growth and necrotized tips of the older leaves in all fertilized treatments.

Consumer Advisory Bulletin, How to Avoid Buying a Salvage, Damaged or Flood Vehicle, August 2011

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Consumer Advisory Bulletin, Some Guidance on Giving Avoiding charity fraud, October 2011

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Consumer Advisory Bulletin, Identity Theft & Medical Identity Theft Target Older Iowans, January 2012

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Anomalous roughening of Hele-Shaw flows with quenched disorder

The kinetic roughening of a stable oil-air interface moving in a Hele-Shaw cell that contains a quenched columnar disorder (tracks) has been studied. A capillary effect is responsible for the dynamic evolution of the resulting rough interface, which exhibits anomalous scaling. The three independent exponents needed to characterize the anomalous scaling are determined experimentally. The anomalous scaling is explained in terms of the initial acceleration and subsequent deceleration of the interface tips in the tracks coupled by mass conservation. A phenomenological model that reproduces the measured global and local exponents is introduced.

Consumer Advisory Bulletin, Beware of A Foreclosure Rescue Scams, February 2012

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Consumer Advisory Bulletin, Don’t Let a Contractor “Put the Fix in” on YOUR Home Repairs & Improvements!, April 2012

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Consumer Advisory Bulletin, A Lesson in For-Profit Colleges, May 2012

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Iowa Energy Savings Guide Saving Energy Saves You Money, 2003

This guide describes things you can do around your home to reduce your utility bills and save you money. It offers some easy, practical steps that you can take to save energy and reduce the cost of heating and cooling your home. There are also tips on ways to reduce your electric and water usage. In addition, energy related health and safety information is also included. So, take a few minutes to read this guide and save it so you can refer to it in the future.