Genome-wide transcriptional responses to shade: Linking shade avoidance and auxin

Plants have the ability to use the composition of incident light as a cue to adapt development and growth to their environment. Arabidopsis thaliana as well as many crops are best adapted to sunny habitats. When subjected to shade, these plants exhibit a variety of physiological responses collectively called shade avoidance syndrome (SAS). It includes increased growth of hypocotyl and petioles, decreased growth rate of cotyledons and reduced branching and crop yield. These responses are mainly mediated by phytochrome photoreceptors, which exist either in an active, far-red light (FR) absorbing or an inactive, red light (R) absorbing isoform. In direct sunlight, the R to FR light (R/FR) ratio is high and converts the phytochromes into their physiologically active state. The phytochromes interact with downstream transcription factors such as PHYTOCHROME INTERACTING FACTOR (PIF), which are subsequently degraded. Light filtered through a canopy is strongly depleted in R, which result in a low R/FR ratio and renders the phytochromes inactive. Protein levels of downstream transcription factors are stabilized, which initiates the expression of shade-induced genes such as HFR1, PIL1 or ATHB-2. In my thesis, I investigated transcriptional responses mediated by the SAS in whole Arabidopsis seedlings. Using microarray and chromatin immunoprecipitation data, we identified genome-wide PIF4 and PIF5 dependent shade regulated gene as well as putative direct target genes of PIF5. This revealed evidence for a direct regulatory link between phytochrome signaling and the growth promoting phytohormone auxin (IAA) at the level of biosynthesis, transport and signaling. Subsequently, it was shown, that free-IAA levels are upregulated in response to shade. It is assumed that shade-induced auxin production takes predominantly place in cotyledons of seedlings. This implies, that IAA is subsequently transported basipetally to the hypocotyl and enhances elongation growth. The importance of auxin transport for growth responses has been established by chemical and genetic approaches. To gain a better understanding of spatio-temporal transcriptional regulation of shade-induce auxin, I generated in a second project, an organ specific high throughput data focusing on cotyledon and hypocotyl of young Arabidopsis seedlings. Interestingly, both organs show an opposite growth regulation by shade. I first investigated the spatio-transcriptional regulation of auxin re- sponsive gene, in order to determine how broad gene expression pattern can be explained by the hypothesized movement of auxin from cotyledons to hypocotyls in shade. The analysis suggests, that several genes are indeed regulated according to our prediction and others are regulated in a more complex manner. In addition, analysis of gene families of auxin biosynthetic and transport components, lead to the identification of essential family members for shade-induced growth re- sponses, which were subsequently experimentally confirmed. Finally, the analysis of expression pattern identified several candidate genes, which possibly explain aspects of the opposite growth response of the different organs.

Cancer incidence in Neuchâtel (2003-2007)

REGISTRATION AREA: The Neuchâtel Cancer Registry covers the Frenchspeaking canton of Neuchâtel in western Switzerland, which shares a border with France. The canton is mainly rural, with only two cities (of approximately 35 000 residents each). Almost all residents are Caucasian; 38% are Protestant and 31% are Catholic. Foreign residents (predominantly of Mediterranean origin) account for about 23% of the population. The main occupational sectors in the canton are watch-making and the microtechnical industry (35%), agriculture (4%), and services (61%). REGISTRY STRUCTURE AND METHODS: The bulk of information is provided by the Neuchâtel Institute of Pathology (INAP) through submission of biopsy, cytology, and autopsy reports. Notiĺcation is voluntary for medical institutions. Additional information is abstracted by the registry staff from computerized hospital charts. The registry routinely integrates abstracts of medical records into its database, and performs periodic electronic linkage between the registry database and the centralized cantonal administrative population database (for the purpose of active follow-up). All death certiĺcates are checked annually against the registry ĺles.

Independencia y educación. Reflexiones en torno al Bicentenario

[spa]El trabajo que presentamos plantea una visión de la educación tras la llamada sublevación de los Pasquines que aparecieron en la ciudad de Santa Fe de Bogotá en 1794. En el artículoanalizamos las propuestas quese ofrecieron por parte de lasautoridades coloniales para hacer frentea los problemasque afectaron al virreinato.Una de las soluciones propuestas para acabar con las opiniones adversas a la corona y al colonialismo pasaba por cambiar los sistemas educativos. Se pretendía volver al sistema anterior a la ilustración y a los nuevos filósofos ya que se temía que en España pasara lo que había sucedido en Francia. La Nueva Filosofía acabó cuestionando los derechos de la monarquía y el descontento social acabó con la vida del monarca y la proclamación de la república. Estas ideas pasaron a las colonias españolas donde algunos ilustrados comenzaban a pensar en repúblicas, poco definidas, cuestionando el orden monárquico. Para evitar el conflicto desde el arzobispado, y la Audiencia se propone acabar con los estudios de la Nueva Filosofía, cerrar las imprentas y la Biblioteca; así mismo, se propone intervenir en el catecismo de la doctrina para introducir preguntas y respuestas que refuercen el papel dela corona y la fidelidad de los súbditos. Este sistema de fidelización de súbditos será empleado posteriormente por las recientes repúblicas para incrementar el patriotismo entre los nuevos ciudadanos.

Bancs de proves per motors de modelisme

Són habituals entre els aeromodelistes les discussions que giren al voltant de la potència dels motors d’explosió i quina hèlix va millor. La manca d’informació tècnica dels motors i de les hèlix fa que aquestes discussions de vegades tinguin una validesa molt limitada, doncs es fonamenten simplement en les sensacions i percepcions subjectives de cadascun dels pilots, sobretot quan es parla de potència. En aquest projecte s’utilitzarà un dinamòmetre inercial, consistent en un volant d’inèrcia el qual s’accelerarà fins assolir les revolucions per minut màximes. La acceleració d’aquest volant mesurat en intervals de temps regulars i conegut el moment d’inèrcia del volant ens permetrà calcular el parell motor i la potència a diferents règims de revolucions per minut. Per altra banda es pretén comparar diferents hèlix muntades en un mateix motor per poder-ne comparar la tracció a diferents revolucions per minut. La tracció es mesurarà utilitzant una cèl·lula de càrrega. Les dades d’ambdós bancs de proves seran recollits i emmagatzemats per un PC amb un software fet a mida per aquest projecte. Una vegada finalitzat cada test es mostraran les dades obtingudes, tant els numèricament com gràficament, permetent a més comparar el resultat de diferents tests, de diferents motors i de diferents hèlix.

Feromones: el paper de l'olor en la comunicació animal

Chemical perception is considered one of the first senses used as a communication system between living organisms. Such communication is based on the emission of signals between a sender and a receiver; if the communication is chemical, these signals are called pheromones. These signals have evolved via natural selection through a mechanism known as ritualization, which converts cues (which are not adapted to communication and which the receiver picks up regardless of the interests of the sender) into signals (information that the sender transmits as an adaptative response to its previously developed perception of the receiver). When communication has evolved between actors (sender and receiver) with common interests, the honesty of the signal is taken for granted, since both want the same thing (i.e., there is no reason to deceive). If the actors have conflicting interests, however, then the possibility of deception seeps into the possible array of adaptations. This can be observed in the case of communicative mimicry. However, in other situations natural selection imposes conditions that screen the possible signals, allowing only those that meet the requirement of honesty to stabilize. These include indices and added-cost signals. The emission of pheromones plays a variety of roles in the life processes of living beings. It facilitates encounters between individuals of the same species and is heavily involved in the mechanisms of recognition of relatives. It also fosters behaviours such as altruism (cooperation between individuals that share a percentage of their genetic inheritance). In many species, including humans, chemical communication works behind the scenes to guide the choice of a sexual partner.

The DYRK-family kinase Pom1 phosphorylates the F-BAR protein Cdc15 to prevent division at cell poles.

Division site positioning is critical for both symmetric and asymmetric cell divisions. In many organisms, positive and negative signals cooperate to position the contractile actin ring for cytokinesis. In rod-shaped fission yeast Schizosaccharomyces pombe cells, division at midcell is achieved through positive Mid1/anillin-dependent signaling emanating from the central nucleus and negative signals from the dual-specificity tyrosine phosphorylation-regulated kinase family kinase Pom1 at the cell poles. In this study, we show that Pom1 directly phosphorylates the F-BAR protein Cdc15, a central component of the cytokinetic ring. Pom1-dependent phosphorylation blocks Cdc15 binding to paxillin Pxl1 and C2 domain protein Fic1 and enhances Cdc15 dynamics. This promotes ring sliding from cell poles, which prevents septum assembly at the ends of cells with a displaced nucleus or lacking Mid1. Pom1 also slows down ring constriction. These results indicate that a strong negative signal from the Pom1 kinase at cell poles converts Cdc15 to its closed state, destabilizes the actomyosin ring, and thus promotes medial septation.

Validació del mètode analític per la determinació d'aminoàcids i carbohidrats d'un producte farmacèutic per HPLC

Per poder desenvolupar un producte farmacèutic és necessari establir un mètode d’anàlisis que permeti determinar i quantificar totes aquelles substàncies que conté, ja sigui referent als principis actius; a les impureses i productes de degradació, conservants, antioxidants,... Grans entitats com la ICH remarquen la importància de validar els mètodes analítics ja que és la via per demostrar que aquell producte compleix les garanties de qualitat prèviament establertes. Així doncs, l’objectiu d’aquest Treball Final de Grau és poder desenvolupar i validar dos mètodes analítics per a la determinació d’aminoàcids i carbohidrats respectivament, d’un producte farmacèutic per cromatografia líquida (HPLC). Per tal de poder concloure que aquell mètode és adequat per la determinació per la qual ha estat desenvolupat, és necessari obtenir resultats que compleixin els criteris d’acceptació corresponents als paràmetres que han de ser avaluats en una validació analítica. Aquests paràmetres són: la precisió, la selectivitat, l’exactitud i la linealitat i el rang. Els resultats d’aquest projecte han demostrat que els dos mètodes desenvolupats són adequats per a la determinació de tres dels principis actius (aminoàcid 1, aminoàcid 2 i carbohidrat 1) que conté el producte farmacèutic d’ús veterinari analitzat; i poden ser validats ja que compleixen els criteris d’acceptació dels paràmetres avaluats que proposa la ICH. El mètode per la determinació de carbohidrats no és vàlid per el carbohidrat 2, ja que durant el desenvolupament es va detectar que una bona part d’aquest passava a carbohidrat 1 (desplaçament de l’equilibri ceto-enòlic que hi ha entre el carbohidrat 1 i el carbohidrat 2 a pHs alts). És per aquest motiu, que es pot concloure que aquest mètode no és vàlid i es recomana seguir investigant per a poder desenvolupar un mètode analític adient.

Les Sentències catòliques del diví poeta Dant (1545) d’en Jaume Ferrer de Blanes: edició crítica del text

Procurador reial i nobiliari, cosmògraf, joier, lapidari, mercader i escriptor, i al capdavall, un ciutadà català honrat, en Ferrer (Vidreres, ~1445 – Blanes, 1529) va marxar de ben jove, primer, a la cort de Nàpols, al servei del rei en Ferran I, i després a la cort de Sicília, al servei de la reina na Joana de Sicília. Acabada aquesta peripècia italiana va tornar a Blanes al servei del vescomte de Cabrera i de Bas fins que va morir a la mateixa vila al 1529. Un seu criat, disset anys més tard, va editar uns papers esparsos que havia trobat a can Ferrer, les (sic) Sentèncias cathòlicas del diví poeta Dant florentí, compilades per lo prudentíssim mossèn Jaume Ferrer de Blanes, incloent-hi tres parts. La primera, Conclusions, és un sumari destinat a mostrar (sic) «Entre totas las cosas necessàries a l’home per aconseguir lo seu fi y beatitut eterna principalment són tres»; la segona, Meditació, és una reflexió a fi d’il•luminar els misteris sobre la passió i mort de Jesucrist a (sic) «lo santíssim loch de Calvari»; la tercera, Letras, és un conjunt de dotze documents, entre cartes i d’altres textos, «fetas a mossèn Jaume Ferrer, respostes e regles per ell ordenades en cosmographia y en art de navegar». En Ferrer, home de grans recursos, fa un recorregut per tots els coneixements que havia acumulat al llarg de la seva vida, de Dant Alighieri a Ptolemeu i del marquès de Santillana a Albert Gran o a Aristòtil, fent servir fragments de la Commedia, dels Proverbios, de la Bíblia i de moltes altres autoritats científiques i filosòfiques, en català, italià, espanyol, llatí i, també, set mots en arameu

Role of human hydroxysteroid (17beta) dehydrogenase type 1 (HSD17B1) in steroid-dependent diseases in females –novel indications for HSD17B1 inhibitors. Phenotypic analysis of transgenic mice overexpressing human HSD17B1.

Hormone-dependent diseases, e.g. cancers, rank high in mortality in the modern world, and thus, there is an urgent need for new drugs to treat these diseases. Although the diseases are clearly hormone-dependent, changes in circulating hormone concentrations do not explain all the pathological processes observed in the diseased tissues. A more inclusive explanation is provided by intracrinology – a regulation of hormone concentrations at the target tissue level. This is mediated by the expression of a pattern of steroid-activating and -inactivating enzymes in steroid target tissues, thus enabling a concentration gradient between the blood circulation and the tissue. Hydroxysteroid (17beta) dehydrogenases (HSD17Bs) form a family of enzymes that catalyze the conversion between low active 17-ketosteroids and highly active 17beta-hydroxysteroids. HSD17B1 converts low active estrogen (E1) to highly active estradiol (E2) with high catalytic efficiency, and altered HSD17B1 expression has been associated with several hormone-dependent diseases, including breast cancer, endometriosis, endometrial hyperplasia and cancer, and ovarian epithelial cancer. Because of its putative role in E2 biosynthesis in ovaries and peripheral target tissues, HSD17B1 is considered to be a promising drug target for estrogen-dependent diseases. A few studies have indicated that the enzyme also has androgenic activity, but they have been ignored. In the present study, transgenic mice overexpressing human HSD17B1 (HSD17B1TG mice) were used to study the effects of the enzyme in vivo. Firstly, the substrate specificity of human HSD17B1 was determined in vivo. The results indicated that human HSD17B1 has significant androgenic activity in female mice in vivo, which resulted in increased fetal testosterone concentration and female disorder of sexual development appearing as masculinized phenotype (increased anogenital distance, lack of nipples, lack of vaginal opening, combination of vagina with urethra, enlarged Wolffian duct remnants in the mesovarium and enlarged female prostate). Fetal androgen exposure has been linked to polycystic ovary syndrome (PCOS) and metabolic syndrome during adulthood in experimental animals and humans, but the genes involved in PCOS are largely unknown. A putative mechanism to accumulate androgens during fetal life by HSD17B1 overexpression was shown in the present study. Furthermore, as a result of prenatal androgen exposure locally in the ovaries, HSD17B1TG females developed ovarian benign serous cystadenomas in adulthood. These benign lesions are precursors of low-grade ovarian serous tumors. Ovarian cancer ranks fifth in mortality of all female cancers in Finland, and most of the ovarian cancers arise from the surface epithelium. The formation of the lesions was prevented by prenatal antiandrogen treatment and by transplanting wild type (WT) ovaries prepubertally into HSD17B1TG females. The results obtained in our non-clinical TG mouse model, together with a literature analysis, suggest that HSD17B1 has a role in ovarian epithelial carcinogenesis, and especially in the development of serous tumors. The role of androgens in ovarian carcinogenesis is considered controversial, but the present study provides further evidence for the androgen hypothesis. Moreover, it directly links HSD17B1-induced prenatal androgen exposure to ovarian epithelial carcinogenesis in mice. As expected, significant estrogenic activity was also detected for human HSD17B1. HSD17B1TG mice had enhanced peripheral conversion of E1 to E2 in a variety of target tissues, including the uterus. Furthermore, this activity was significantly decreased by treatments with specific HSD17B1 inhibitors. As a result, several estrogen-dependent disorders were found in HSD17B1TG females. Here we report that HSD17B1TG mice invariably developed endometrial hyperplasia and failed to ovulate in adulthood. As in humans, endometrial hyperplasia in HSD17B1TG females was reversible upon ovulation induction, triggering a rise in circulating progesterone levels, and in response to exogenous progestins. Remarkably, treatment with a HSD17B1 inhibitor failed to restore ovulation, yet completely reversed the hyperplastic morphology of epithelial cells in the glandular compartment. We also demonstrate that HSD17B1 is expressed in normal human endometrium, hyperplasia, and cancer. Collectively, our non-clinical data and literature analysis suggest that HSD17B1 inhibition could be one of several possible approaches to decrease endometrial estrogen production in endometrial hyperplasia and cancer. HSD17B1 expression has been found in bones of humans and rats. The non-clinical data in the present study suggest that human HSD17B1 is likely to have an important role in the regulation of bone formation, strength and length during reproductive years in female mice. Bone density in HSD17B1TG females was highly increased in femurs, but in lesser amounts also in tibias. Especially the tibia growth plate, but not other regions of bone, was susceptible to respond to HSD17B1 inhibition by increasing bone length, whereas the inhibitors did not affect bone density. Therefore, HSD17B1 inhibitors could be safer than aromatase inhibitors in regard to bone in the treatment of breast cancer and endometriosis. Furthermore, diseases related to improper growth, are a promising new indication for HSD17B1 inhibitors.

Thylakoid Protein Phosphorylation in Regulation of Photosynthesis

Once the seed has germinated, the plant is forced to face all the environmental changes in its habitat. In order to survive, plants have evolved a number of different acclimation systems. The primary reaction behind plant growth and development is photosynthesis. Photosynthesis captures solar energy and converts it into chemical form. Photosynthesis in turn functions under the control of environmental cues, but is also affected by the growth, development, and metabolic state of a plant. The availability of solar energy fluctuates continuously, requiring non-stop adjustment of photosynthetic efficiency in order to maintain the balance between photosynthesis and the requirements and restrictions of plant metabolism. Tight regulation is required, not only to provide sufficient energy supply but also to prevent the damage caused by excess energy. The very first reaction of photosynthesis is splitting of water into the form of oxygen, hydrogen, and electrons. This most fundamental reaction of life is run by photosystem II (PSII), and the energy required for the reaction is collected by the light harvesting complex II (LHCII). Several proteins of the PSII-LHCII complex are reversibly phosphorylated according to the energy balance between photosynthesis and metabolism. Thylakoid protein phosphorylation has been under extensive investigation for over 30 years, yet the physiological role of phosphorylation remains elusive. Recently, the kinases behind the phosphorylation of PSII-LHCII proteins (STN7 and STN8) were identified and the knockout mutants of these kinases became available, providing powerful tools to elucidate the physiological role of PSII-LHCII phosphorylation. In my work I have used the stn7 and stn8 mutants in order to clarify the role of PSII-LHCII phosphorylation in regulation and protection of the photosynthetic machinery according to environmental cues. I show that STN7- dependent PSII-LHCII protein phosphorylation is required to balance the excitation energy distribution between PSII and PSI especially under low light intensities when the excitation energy transfer from LHC to PSII and PSI is efficient. This mechanism differs from traditional light quality-induced “state 1” – “state 2” transition and ensures fluent electron transfer from PSII to PSI under low light, yet having highest physiological relevance under fluctuating light intensity. STN8-dependent phosphorylation of PSII proteins, in turn, is required for fluent turn-over of photodamaged PSII complexes and has the highest importance upon prolonged exposure of the photosynthetic apparatus to excess light.

Turhan kunnianhimoinen yleisesitys

Kirjallisuusarvostelu

Roomalaiskatolista ekumeniaa saksalaisin voimin

Kirjallisuusarvostelu

Onnistunut esitys värittömistä piispoista

Kirjallisuusarvostelu

Täystehokonvertterin tehohäviöt ja hyötysuhde

Diplomityössä perehdytään tuuliturbineissa käytettyjen täystehokonvertterien tehohäviöihin ja hyötysuhteeseen. Täystehokonvertterissa generaattorin tuottama sähköteho tasasuunnataan hyvällä hyötysuhteella aktiivisella geenraattorisillalla konvertterin välipiiriin ja edelleen vaihtosuunnataan aktiivisella verkkovaihtosuuntaajasillalla siirtoverkkoon. Työn tarkoituksena on antaa yleiskuva tehohäviöiden jakautumisesta ja yksinkertaistaa niiden laskentaa. Häviömekanismit ja häviöiden määräytyminen esitellään pääkomponenttitasolla. Tehohäviöiden osalta keskitytään erityisesti muuntajateräksestä valmistettujen sinisuotimien ja du/dt-suotimien rautahäviöihin. Ongelmana rautahäviöiden määrittämisessä on korkeilla taajuuksilla tapahtuvat häviöt, joiden laskentaan ei ole yleensä saatavilla tarvittavia materiaaliparametrejä. Tehohäviöiden laskentaa varten toteutettu laskentasovellus on esitelty periaatteellisina vuokaavioina ja sovelluksella saatavia tuloksia on esitetty ja vertailtu mitattuihin tuloksiin.

Evaluating the Advantages of Implementing a CRM solution

CRM-järjestelmän avulla pyritään yleisesti tehostamaan liiketoimintaprosesseja. Yrityksestä, kuin myös toimialasta riippuen hyödyt sekä tavoitteet vaihtelevat jonkin verran. Usein CRM-järjestelmän avulla saavutettavien hyötyjen mittaaminen ja arviointi organisaatiossa koetaan hankalaksi ja täten todellinen hyötyjen arviointi jää suppeaksi. Tämän tutkimuksen tavoitteena oli kartoittaa etuja, joita CRM-järjestelmän käyttöönotto on todellisuudessa tuonut yrityksille. Tutkimus kulminoituu laskentamalliin, jonka avulla CRM käytön hyödyt konvertoidaan konkreettiseksi rahasummaksi. Tutkimuksessa pyritään vastaamaan seuraaviin tutkimuskysymyksiin: 1. Kun yritys suunnitteli CRM-sovelluksen käyttöönottoa, mitkä olivat järjestelmälle asetetut tavoitteet? 2. Onko yritys saavuttanut CRM-järjestelmälle asetetut tavoitteet? 3. Onko yritys saavuttanut odottamattomia hyötyjä CRM-järjestelmän käytön avulla? 4. Mitkä ovat CRM-järjestelmän tärkeimmät kehityskohteet käyttökokemusten perusteella? Tutkimus perustuu CRM-kirjallisuuden avulla luotuun teoriaviitekehykseen. Teoriaviitekehyksen pohjalta luotiin ideaalimalli ja mallin pohjalta web-survey -kysely. Kyselyn tulosten perusteella toteutettiin haastatteluja, joilla pyrittiin saamaan tutkimustuloksiin syvyyttä.