Le virus d'immunodéficience humaine 1 (VIH-1) cible spécifiquement les cellules CD4+ et empêche ainsi l'activation de cellules T cytotoxiques et B lors d'une infection secondaire. Le VIH-1 antagonise également la plupart des facteurs de restriction de l'hôte, y compris la tétherine. En l'absence de la protéine virale Vpu, la tétherine inhibe le relarguage de particules virales et provoque leur dégradation. La tétherine est également capable d'induire une signalisation pro-inflammatoire en réponse au bourgeonnement viral ainsi que d'activer le récepteur de cellules dendritiques ILT7. L'objectif principal de cette étude consistait à élucider les bases structurales de l'interaction entre la tétherine et ILT7. Malgré de nombreuses difficultés rencontrées dans la production recombinante de ILT7, on a pu déterminer la structure cristallographique du domaine N-terminale du récepteur. La ligation de la tétherine à l'ectodomaine entier de ILT7, mais pas au domaine N-terminal, a également été montré. Ces résultats constituent une base solide pour la caractérisation plus détaillée de l'interaction. / Human immunodeficiency virus 1 (HIV-1) specifically infects CD4+ T cells, thereby preventing an appropriate activation of cytotoxic T cells and B cells in response to opportunistic pathogens. In addition, HIV-1 antagonises host restriction factors, including tetherin. In the absence of the viral protein Vpu, tetherin potently inhibits virus particle release from infected cells. Tetherin also triggers proinflammatory signaling upon sensing virus assembly, and activates the dendritic cell receptor ILT7. The principal objective of this thesis was to elucidate the structural details underlying the interaction of tetherin with ILT7. Despite difficulties in the production of recombinant ILT7, the crystal structure of the N-terminal ILT7 domain could be determined. Furthermore, binding of tetherin to full-length ILT7, but not to the N-terminal domain, could be confirmed by SPR. These results provide a solid basis for the more detailed characterisation of the interaction.

Submitted by DANIEL NUNES DA SILVA null (dnunes@iac.sp.gov.br) on 2016-02-03T16:13:39Z No. of bitstreams: 1 Dissertação_Daniel_Nunes_da_Silva.pdf: 6745302 bytes, checksum: 77ecd4c14b47b559fa28ad6747334592 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-02-04T15:52:16Z (GMT) No. of bitstreams: 1 silva_dn_me_jabo.pdf: 6745302 bytes, checksum: 77ecd4c14b47b559fa28ad6747334592 (MD5) / Made available in DSpace on 2016-02-04T15:52:16Z (GMT). No. of bitstreams: 1 silva_dn_me_jabo.pdf: 6745302 bytes, checksum: 77ecd4c14b47b559fa28ad6747334592 (MD5) Previous issue date: 2015-12-11 / A irrigação de salvamento é uma prática agronômica muito utilizada nos canaviais, nas regiões que apresentam altos déficits hídricos. O Estado de Goiás faz uso desta prática para evitar quedas acentuadas de produtividades após ciclo nos canaviais cortados em períodos de déficits hídricos. A partir de mudas pré-brotadas, este trabalho teve por objetivo estudar qual (ais) dos 16 genótipos apresenta (m) maior resposta e tolerância quando exposto (s) a diferentes frequências de aplicação (7; 14; 28 dias e sem irrigação) da irrigação de salvamento no ciclo de cana-soca de 1º corte. O período de avaliação foi de novembro de 2013 a junho de 2015. O experimento foi instalado na Usina Jalles Machado, no município de Goianésia-GO, localizada no norte do Estado de Goiás, em delineamento quadrado latino 4 x 4, com 16 genótipos e 4 repetições. Os atributos analisados foram: notas visuais de brotação de soqueira, número de colmos, diâmetro e altura dos colmos, produtividades (TCH final) e suas respectivas quedas percentuais (%) quando comparado aos tratamentos com a frequência de 7 dias e sem irrigação. A lâmina- -padrão utilizada na irrigação de salvamento foi de 60 mm. Os resultados obtidos mostraram que os genótipos mais responsivos à irrigação de salvamento foram: CTC4, IACSP93-3046 e RB867515, e os menos responsivos foram CTC9003, RB98710 e IAC87-3396. Os genótipos IACSP95-5094 e CTC9003 foram os mais tolerantes ao déficit hídrico. A frequência da aplicação da irrigação de salvamento após a colheita, com intervalos de aplicação variando entre 7; 14 e 28 dias, não promoveu incremento na TCH final, promovendo maior flexibilidade (em dias) no momento de execução na lavoura comercial. O atributo produtividade (TCH final) só obteve impacto negativo quando não foi aplicada nenhuma lâmina de irrigação de salvamento. O atributo biométrico perfilhos finais, avaliado no momento da colheita, não apresentou diferenças estatísticas nas frequências de aplicação da irrigação de salvamento com 7; 14 e 28 dias, e sem irrigação. Os atributos biométricos analisados (altura final e diâmetro final), avaliados no momento da colheita, não apresentaram diferenças estatísticas nos intervalos de aplicação da frequência de salvamento com 7; 14 e 28 dias, diferenciando-se apenas do tratamento sem irrigação. / The salvage irrigation is an agronomic practice widely used in the cane fields in regions with high water deficits. The state of Goiás is done using this practice to avoid sharp drops in yields cycle after cycle in sugarcane cut in periods of water deficits. From pre-sprouted seedlings, this study aimed to study what (es) of 16 genotypes had higher responses and tolerance when exposed to different application frequency (7, 14 and 28 days and without irrigation) Rescue irrigation in the cycle cane ratoon 1st cut. The evaluation period was from November 2013 to June 2015. The experiment was installed in Jalles Machado plant in Goianésia-GO, municipality located in the northern state of Goiás, in Latin square design 4 x 4, with 16 genotypes and four repetitions. The attributes were analyzed: visual notes sprouting from the stump, number of stems, diameter and height of the stems, productivity (final TCH) and their respective falls (%) compared to treatment with the frequency of 7 days and without irrigation. The standard blade used in rescue irrigation was 60 mm. The results showed that the most responsive to salvage irrigation genotypes were CTC4, IACSP93-3046 and RB867515, and were less responsive CTC9003, RB98710 and IAC87-3396. The IACSP95-5094 and CTC9003 genotypes were the most tolerant to drought. The frequency of application of salvage irrigation after harvest with application intervals ranging from 7, 14 and 28 days, did not cause an increase in the final TCH promoting greater flexibility (in days) at the time of execution in commercial farming. The productivity attribute (final TCH) only obtained negative impact when it was not applied any blade salvage irrigation. The biometric attribute final tiller, valued at harvest, showed no statistical differences in the application of frequencies rescue irrigation with 7, 14 and 28 days and without irrigation. Biometric attributes examined (final height and final diameter) evaluated at harvest showed no statistical differences in the application intervals of the rescue frequency with 7, 14 and 28 days, differing only without irrigation treatment.

Abstract Prognostic features of colorectal cancer (CRC) are important for determining the optimal treatment for an individual patient. This study was carried out to evaluate the significance of the prognostic significance of inflammatory cell reaction and tumour budding at the invasive front of the tumour in CRC patients, to study the pattern of alterations in the serum cytokine levels of CRC patients compared to healthy controls, and to evaluate whether the patterns of the cytokine levels alter according to the stage of disease. Study material consists of a series of CRC patients operated in Oulu University Hospital (N=466, studies I-II, and N=148, study III). The intensities of inflammatory cell reaction and tumour budding were estimated and the association of these features with survival was analysed (I-II). Preoperative serum samples were collected from patients and age- and sex-matched controls, and concentrations of 13 cytokines and chemokines were analysed (III). Inflammatory cell reaction and tumour budding at the tumour invasive margin were independent prognostic markers in CRC. In patients with stage I-II disease, high-grade inflammation was associated with better 5-year survival (87.6%) than low-grade inflammation (47.0%). Tumour budding was present in 24.0% of cases and predicted worse 5-year survival (15.4% in contrast to 63.5%). Serum levels of PDGF, IL-6, IL-7, and IL-8 were higher, and levels of MCP-1 were lower in CRC patients compared to controls. A pattern of five most predictive cytokines reached an excellent capacity in discriminating patients from healthy controls and reached an AUC of 0.890 in the ROC analysis. High-stage CRC was associated with increased levels of IL-6, IL-8 and IL-1ra, and metastasised disease was accompanied by an orientation to Th2 cytokine milieu. According to this study, patients with CRC can be stratified into different prognostic groups by assessing inflammatory cell reaction and tumour budding at the invasive front of the tumour. Evaluation of these features may give additional information for making treatment decisions. Serum cytokine profile was shown to change during cancer progression and seems promising in separating CRC patients from healthy controls, but its clinical value is yet to be confirmed. / Tiivistelmä Kasvaimen ennusteeseen vaikuttavien tekijöiden tunteminen on tärkeää syöpäpotilaan yksilöllisen hoidon suunnittelussa. Tässä tutkimuksessa selvitettiin kasvaimen tulehdusreaktion ja kasvaimen reunan silmuilevan kasvutavan merkitystä kolorektaalisyöpäpotilaiden ennusteeseen. Lisäksi tutkimuksessa mitattiin tulehdusreaktion välittäjäaineiden, seerumin sytokiinien, pitoisuuksia potilailla ja verrokeilla sekä näiden pitoisuuksien vaihtelua suhteessa syövän levinneisyyteen. Tutkimusaineisto koostui Oulun yliopistollisessa sairaalassa leikatuista kolorektaalisyöpäpotilaista (N=466, tutkimukset I–II, N=148, tutkimus III). Kasvainnäytteistä tutkittiin kasvaimen tulehdusreaktion ja silmuilevan kasvutavan voimakkuutta ja arvioitiin näitä piirteitä suhteessa potilaiden elinaikatietoihin (tutkimukset I–II). Potilaiden ja verrokkihenkilöiden seeruminäytteistä mitattiin 13 sytokiinin pitoisuudet (tutkimus III). Kasvaimen tulehdusreaktio ja silmuileva kasvutapa osoittautuivat itsenäisiksi ennustetekijöiksi. Potilailla oli parempi 5-vuotisennuste (87.6 %), jos kasvaimen tulehdusreaktio oli voimakas verrattuna tapauksiin, joissa tulehdusreaktio oli heikko (47.0 %). 24 %:ssa kasvaimista kasvutapa oli silmuileva, ja näillä 5-vuotisennuste oli huonompi kuin ei-silmuilevissa (15.4 % vs. 63.5 %). Potilailla todettiin korkeammat seerumin PDGF, IL-6, IL-7, ja IL-8 -pitoisuudet ja matalammat MCP-1 -pitoisuudet kuin verrokeilla. Mittaamalla viiden ennustearvoltaan merkitsevimmän sytokiinin pitoisuudet voitiin potilaat luotettavasti erottaa verrokeista ROC-analyysin avulla, kun ROC-käyrän alle jäävä pinta-ala oli 0.890 %. Pidemmälle levinneissä taudeissa todettiin korkeampia IL-6, IL-8 ja IL-1ra -pitoisuuksia, ja etäpesäkkeisissä taudeissa sytokiinipitoisuudet muuttuivat Th2 -profiilin suuntaiseksi. Tutkimuksen mukaan kasvaimen tulehdusreaktion ja silmuilevan kasvutavan arvioinnilla kolorektaalisyöpäpotilaat voidaan jakaa ennusteellisiin ryhmiin, mitä on mahdollista hyödyntää hoidon suunnittelussa. Seerumin sytokiiniprofiilin osoitettiin muuttuvan taudin edetessä, ja sytokiinien pitoisuudet poikkeavat kolorektaalisyöpäpotilailla verrattuna terveiltä verrokeilta mitattuihin arvoihin.

Abstract Colorectal cancer is the second most common malignancy in the Western World. The overall 5-year survival is still only 50–60%. Thus, better prognostic markers are needed to improve survival of the disease. Most colorectal cancers develop from pre-existing adenomas including conventional, flat and serrated adenomas. The most important prognostic factors include tumour stage, histologic subtype and poor differentiation. The prognosis of colorectal cancer depends mainly on tumour stage. The growth of colorectal cancer is determined by cell proliferation, differentation and apoptosis. The progression of colorectal cancer is associated with the growth pattern of colorectal cancer and its invasive margin. Cancer cell budding means the presence of cells scattered in the stroma at the invasive margin, and is associated with β-catenin, an adhesion protein involved in the nuclear Wnt/β-catenin pathway. Hormones may be directly involved in the growth of a cancer, for example sex hormones play an important role in the development of most gynaecological cancers. The knowledge about the dependency of cancers on other hormones, such as thyroid hormones, is limited. This thesis focuses on factors affecting growth and prognosis in colorectal cancer. Antibodies for Ki-67, caspase cleavage site for keratin 18, β-catenin and TRβ1 were used to determine their possible associations with colorectal cancer growth patterns and the characteristics of the invasive margin. Apoptosis and proliferation were decreased at the invasive margin, particularly in serrated adenocarcinomas. The invasive margin showed a presence of budding cell clusters in 24.0% of the cases and this predicted a very poor 5-year-survival (15.4%, P < 0.00001), but nuclear β-catenin accumulation did not predict budding. Thyroid hormone receptor TRβ1 was associated with polypoid growth, presence of KRAS mutations and also with a higher WHO histological grade and advanced Dukes' stage, and in in vitro analysis, thyroid hormone T3 had a modulatory effect on colorectal cancer cell protein synthesis and apoptosis. In conclusion, the growth type of colorectal cancer, i.e. conventional polypoid, flat or serrated, has an association with the characteristics of the invasive margin. Budding margin is associated with poor prognosis in colorectal cancer, and could be utilised in diagnostic pathology. Association of TRβ1 expression with polypoid growth pattern and the presence of KRAS mutations suggest that abnormalities in thyroid hormone signalling involving TRβ1 play a role in the development of some types of colorectal adenocarcinomas.

Heterochromatin in the budding yeast Saccharomyces cerevisiae is composed of polymers of the SIR (Silent Information Regulator) complex bound to nucleosomal DNA. Assembly of heterochromatin requires all three proteins of the Sir complex: the histone deacetylase Sir2, and histone binding proteins Sir3 and Sir4. Heterochromatin establishment requires passage through at least one cell cycle, but is not dependent on replication. Inhibition of chromatin modifying enzymes may be a mechanism for how cells limit assembly. Dot1 dependent methylation of H3K79 is suggested to inhibit de novo assembly. Halving the levels of Sir4 in cells causes a loss of silencing, suggesting that Sir4 protein abundance regulates the assembly of heterochromatin. We examine de novo assembly using a single cell assay. Half the level of Sir4 affects establishment, but not the maintenance, of silencing at HM loci. Additional Sir4 accelerates the rate of assembly. Epistasis analysis suggests that Dot1 dependent chromatin modification may act upstream of Sir4 abundance. We hypothesize that dot1Δ mutants speed assembly by disrupting telomeric heterochromatin, which liberates Sir4 to act at the HM loci. Deletion of YKU70, which specifically disrupts telomeric silencing, also speeds de novo assembly, without altering the methylation of histone H3. Consistent with our model, we have shown that Sir4 abundance falls during pheromone and stationary phase arrests after which several cell cycles are required before silencing can be reestablished.

No description available.

A identificação histopatológica dos agentes fúngicos é um método excelente de diagnóstico, devido ao fato de que as estruturas são facilmente identificadas por meio das técnicas histoquímicas. Até o momento, não dispõem-se de métodos aceitáveis para quantificação da atividade da infecção. Esta investigação protocola um método de estimativa para atividade biológica da criptococose através da determinação dos índice de brotamentos e carminofílico do Cryptococcus. Objetivos: Descrever os aspectos histopatológicos da criptococose através das técnicas histoquímicas básicas e especiais da micologia. Métodos: Foram avaliados 33 pacientes com diagnóstico histopatológico prévio da criptococose. Resultados: Houve predominância do sexo masculino. A idade variou entre 10 a 81 anos, com média de 45,6 anos. A criptococose é doença definidora dos casos de Aids, sendo considerado seu principal fator predisponente, seguido de transplantes. O trato respiratório é o mais envolvido. O microrganismos tem tropismo para o sistema nervoso central e apresenta disseminação para outros órgãos. Resultados falso-negativos é reflexo da deficiência de material capsular. A mortalidade foi de 36%, sendo o maior índice obervado até os 3 primeiros meses após o diagnóstico. A criptococose apresenta-se sob duas formas, reativa e paucireativa. Na infecção reativa, os organismos foram menos abundantes e predominantemente intracelulares aos histiócitos e às células gigantes. Na infecção paucireativa, há um grande número de leveduras, que proliferam-se extracelularmente e estão associadas a destruição do tecido afetado. Ambos infecções, reativas e paucireativas mostraram grande variação no índice de brotamento. O índice carminofílico foi menor nas infecção reativas, quando comparados a infecção paucireativa. Discussão: A coloração de Hematoxilina-Eosina é usada para visualizar as alterações estruturais das lesões, bem como da reação tecidual. A coloração da prata é a mais utilizada para identificação dos organismos fúngicos como o Cryptococcus. A coloração de Mucicarmim de Mayer detecta a cápsula mucopolissacarídica circundante corada na cor magenta. A coloração de FM oferece diagnóstico diferencial nos casos inconclusivos à coloração de Mucicarmim de Mayer. A quantificação de IB e IC é uma escala útil na interpretação da resposta inflamatória do hospedeiro e atividade biológica da criptococose. / The histopathologic identification from the fungal agents that's a method excellent of diagnostic, due the fact of what the structures são easily identified for histochemical techniques. So far, there is no methods you accepted about to measurement of biologic activity. This investigation aponta to an method of estimate of the activity biologic of cryptococcal infection by determination of the Budding Index and Carminophilic Index of the Cryptococcus. Objectives: Describes the histologic features of cryptococcosis by basic and special histochemical techniques of mycology. Methods: Have been evaluated 33 patients with previous cryptococcosis histopathologic diagnostic. Results: There is an predominance of the males. The age of the patients ranged from 10 to 81 years with a median value 45,4 years. The HIV infection was the main risk factor for disease, followg of transplants. The respiratory tract is the most frequently involved among the organ systems organs. The false-negative latex test are due to capsular deficiency. The moratlity rate was 36%, The high rate of 50% was observed between of 1 to 3 months. The cryptococcal infections is divided into two major histologic categories, reactive and paucireactive, based upon the host reaction. In reactive infection, the organisms were lessa abundant and were predominantly intracellular within histiocytes and giant cells. In paucireactive infection, thre is large numbers of yeats in the lesions, cryptococci proliferate extracellarly within the involved tissues, associated histologically with mucoid degeneration of the surrounding tissue. Both reactice and paucireactive infections showed great variation in Budding Index. The Carminophilic Inded was lower in the reactive infections, when compared with the paucireactive infection. In this Carminophilic Index presented higher measurements.. Discussion: The Hematoxilin-Eosin stain is used to look for strucutural changes of the infectd lesion, as well tissues reactions. The Gomori’s methenamine-silver stain is the more commonly used in identificatifying these organisms. The mucicarmine stain detecting the surrounding mucopolisacharides capsule of the magenta color. The Fontana-Masson staining offers differential diagnostic. The determination of IB and IC is an scale that relied, because it provides an interpretation of the host response and biological activity of the cryptoccosis.

<p>Intracellular membrane trafficking is regulated by a large number of protein complexes and lipids. Blocking of trafficking disrupts normal membrane dynamics and causes membrane stress. Two similar proteins from <i>Saccharomyces cerevisiae</i>, Myr1 and Smy2, each containing a polyproline-binding GYF domain, were discovered in separate screens for dosage suppressors of trafficking mutations. The functions of GYF domain proteins are poorly described despite its determined structure and a number of known polyproline peptide ligands. We predicted, using computational analysis, associations between mRNA decay factors and both Myr1 and Smy2, and further demonstrated that they localize to sites of mRNA degradation upon stress, in a GYF domain dependent manner.</p><p>Ypt6 is a small GTPase that regulates vesicle docking at the late Golgi in budding yeast. Myr1 was found as a novel suppressor during the screening of a genomic library in a null ypt6 mutant. Myr1 additionally was capable of rescuing the temperature sensitive growth of a Ric1 deficient strain. Importantly, Ric1 is an activator of Ypt6 and is synthetic lethal with Myr1. Biochemical characterization of the Myr1 protein revealed a limited solubility and an ability to bind cellular membranes, likely relevant to the rescue of trafficking mutants.</p><p>We further assayed the affinity of Myr1 domains to liposomes of distinct composition. Preference for negatively charged lipids suggested possible electrostatic interactions with polybasic clusters within C-terminal regions of Myr1. In contrast, the N-terminus with the GYF domain was found to be capable of self-association. Membrane stress caused by a lipid-bilayer perturbing drug resulted in induced formation of mRNA processing bodies. Cumulatively, these studies suggest that Myr1 functions in the regulation of mRNA stability via its GYF domain, and can sense membrane stress by binding to the lipid bilayer.</p>

Intracellular membrane trafficking is regulated by a large number of protein complexes and lipids. Blocking of trafficking disrupts normal membrane dynamics and causes membrane stress. Two similar proteins from Saccharomyces cerevisiae, Myr1 and Smy2, each containing a polyproline-binding GYF domain, were discovered in separate screens for dosage suppressors of trafficking mutations. The functions of GYF domain proteins are poorly described despite its determined structure and a number of known polyproline peptide ligands. We predicted, using computational analysis, associations between mRNA decay factors and both Myr1 and Smy2, and further demonstrated that they localize to sites of mRNA degradation upon stress, in a GYF domain dependent manner. Ypt6 is a small GTPase that regulates vesicle docking at the late Golgi in budding yeast. Myr1 was found as a novel suppressor during the screening of a genomic library in a null ypt6 mutant. Myr1 additionally was capable of rescuing the temperature sensitive growth of a Ric1 deficient strain. Importantly, Ric1 is an activator of Ypt6 and is synthetic lethal with Myr1. Biochemical characterization of the Myr1 protein revealed a limited solubility and an ability to bind cellular membranes, likely relevant to the rescue of trafficking mutants. We further assayed the affinity of Myr1 domains to liposomes of distinct composition. Preference for negatively charged lipids suggested possible electrostatic interactions with polybasic clusters within C-terminal regions of Myr1. In contrast, the N-terminus with the GYF domain was found to be capable of self-association. Membrane stress caused by a lipid-bilayer perturbing drug resulted in induced formation of mRNA processing bodies. Cumulatively, these studies suggest that Myr1 functions in the regulation of mRNA stability via its GYF domain, and can sense membrane stress by binding to the lipid bilayer.

The Sli15-Ipl1-Bir1 chromosomal passenger complex is essential for proper kinetochore-microtubule attachment and spindle stability in the budding yeast Saccharomyces cerevisiae. Subcellular localization of this complex during anaphase is regulated by the Cdc14 protein phosphatase, which is kept inactive in the nucleolus until anaphase onset. I show here that the predominantly nucleolar ribosome biogenesis protein Utp7 is also present at kinetochores and is required for normal organization of kinetochore proteins and proper chromosome segregation. Utp7 associates with and regulates the localization of Sli15 and Cdc14. It prevents the abnormal localization of Sli15 on cytoplasmic microtubules, the premature concentration of Sli15 on the pre-anaphase spindle, and the premature nucleolar release of Cdc14 before anaphase onset. Utp7 regulates Sli15 localization not entirely through its effect on Cdc14. Furthermore, the mitotic exit block caused by Cdc14 inactivation is relieved partially by the simultaneous inactivation of Utp7. Thus, Utp7 is a multifunctional protein that plays essential roles in the vital cellular processes of ribosome biogenesis, chromosome segregation and cell cycle control. Protein phosphatase 1, Glc7 opposes in vivo functions of the Ipl1-Sli15-Bir1 kinase complex in budding yeast. I show here Scd5- a targeting subunit of Glc7 that regulates endocytosis/cortical actin organization and undergoes nuclear-cytoplasmic shuttling- is present at kinetochores. Ipl1 associates with both Glc7 and Scd5. The scd5-PP1[Delta]2 mutation, which disrupts the association between Glc7 and Scd5, also disrupts the association between Ipl1 and Scd5-Glc7 without affecting the kinetochore localization of these proteins. Genetic studies suggest that Scd5 may positively regulate both Glc7 phosphatase and the Ipl1 kinase complex. In accordance, Scd5 stimulates in vitro kinase activity of Ipl1. scd5-PP1[Delta]2 cells missegregate chromosomes severely due to several defects: i) at least one of sister kinetochores appears not attached to microtubule. ii) sister chromatids are persistently cohesed through anaphase. iii) Sli15 is hyperphosphorylated and less abundant on the anaphase spindle resulting in unstable mitotic spindle. These results together suggest that Scd5 functions in diverse processes that are essential for faithful chromosome segregation. How Scd5 coordinately regulates two apparently antagonistic enzymatic activities of Ipl1 and Glc7 remains to be determined. / text