A cell sizer network involving Cln3 and Far1 controls entrance into S phase in the mitotic cycle of budding yeast

Saccharomyces cerevisiae must reach a carbon source-modulated critical cell size, protein content per cell at the onset of DNA replication (Ps), in order to enter S phase. Cells grown in glucose are larger than cells grown in ethanol. Here, we show that an increased level of the cyclin-dependent inhibitor Far1 increases cell size, whereas far1Δ cells start bud emergence and DNA replication at a smaller size than wild type. Cln3Δ, far1Δ, and strains overexpressing Far1 do not delay budding during an ethanol glucose shift-up as wild type does. Together, these findings indicate that Cln3 has to overcome Far1 to trigger Cln–Cdc28 activation, which then turns on SBF- and MBF-dependent transcription. We show that a second threshold is required together with the Cln3/Far1 threshold for carbon source modulation of Ps. A new molecular network accounting for the setting of Ps is proposed

Mortalidade por paracoccidioidomicose no Brasil (1980-1995)

This study analyzes 3,181 deaths from paracoccidioidomycosis in Brazil, based on 16 years of sequential data (from 1980 to 1995). During this period paracoccidioidomycosis showed considerable magnitude and low visibility, representing the eighth most common cause of death from predominantly chronic or recurrent types of infectious and parasitic diseases. It also had the highest mortality rate among the systemic mycoses. The mean annual mortality rate was 1.45 per million inhabitants, indicating a downward long-term trend (reduction of 31.28%), while spatial distribution among the different regions and States of Brazil was non-homogenous. The South (with the highest regional rate) and the Southeast showed a downward trend, while the Central West had the second highest rate in the country. At least one-fifth of Brazilian municipalities (or 22.71% of the country's total area) reported deaths from paracoccidioidomycosis. Overall nationwide mortality per area was 3.73/10,000km². The disease was endemic in non-metropolitan areas. The majority of deaths occurred in males (84.75%), and there was a sex ratio of 562 men/100 women. The 30-59-year and over-60-year age groups were the most affected. The study showed that the mortality rate justifies classifying this disease as a major health problem in Brazil.Foram estudados 3.181 óbitos por paracoccidioidomicose no Brasil, a partir de séries temporais de 16 anos (1980-1995). No período, esta micose mostrou grande magnitude e baixa visibilidade, destacando-se como oitava causa de mortalidade por doença predominantemente crônica ou repetitiva, entre as infecciosas e parasitárias, e a mais elevada taxa de mortalidade entre as micoses sistêmicas. A taxa de mortalidade média anual foi de 1,45/milhão de habitantes, com tendência secular em queda (redução de 31,28%), a distribuição espacial não foi homogênea entre as diferentes regiões e Estados. O Sul, com a maior taxa regional, e o Sudeste apresentaram tendência a queda. A Região Centro-Oeste teve o segundo coeficiente mais alto do País, com tendência a ascensão. Houve registro de óbitos pela endemia em cerca de um quarto dos municípios brasileiros, estendendo-se por 22,71% de sua área. A densidade geral de óbitos foi de 3,73 óbitos/10.000km². A doença prevaleceu como endemia nas áreas não metropolitanas. A taxa de mortalidade predominou em indivíduos do sexo masculino, com 84,75% dos óbitos e razão de masculinidade de 562 homens/100 mulheres. O grupo etário entre 30-59 anos foi o mais atingido, seguido dos indivíduos com 60 anos ou mais. O estudo mostrou que a taxa de mortalidade pode ser considerada como indicador para definir a doença como importante agravo de saúde no Brasil.Fundação Oswaldo Cruz Escola Nacional de Saúde Pública Centro de Saúde Escola Germano Sinval FariaFundação Oswaldo Cruz Escola Nacional de Saúde Pública Departamento de Endemias Samuel PessoaFundação Oswaldo Cruz Centro de Pesquisa Hospital Evandro Chagas Serviço de MicologiaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de DermatologiaUNIFESP, EPM, Depto. de DermatologiaSciEL

Rim15 and the crossroads of nutrient signalling pathways in Saccharomyces cerevisiae

In recent years, the general understanding of nutrient sensing and signalling, as well as the knowledge about responses triggered by altered nutrient availability have greatly advanced. While initial studies were directed to top-down elucidation of single nutrient-induced pathways, recent investigations place the individual signalling pathways into signalling networks and pursue the identification of converging effector branches that orchestrate the dynamical responses to nutritional cues. In this review, we focus on Rim15, a protein kinase required in yeast for the proper entry into stationary phase (G(0)). Recent studies revealed that the activity of Rim15 is regulated by the interplay of at least four intercepting nutrient-responsive pathways

Primeiro registro de Cryptococcus neoformans em excretas de pombos provenientes de locais públicos e residenciais de área metropolitana de Cuiabá, Estado do Mato Grosso, Brasil

RESUMO A criptococose é micose sistêmica potencialmente grave causada por duas espécies do gênero Cryptococcus que acometem tanto homens como animais: Cryptococcus neoformans e C. gattii. São infecções cosmopolitas e emergentes, resultantes da interação do hospedeiro - humano e animal versus meio ambiente. A proposta deste trabalho foi avaliar a ocorrência de C. neoformans em 122 amostras de excretas secas de pombos coletadas em 49 locais na cidade de Cuiabá, Estado do Mato Grosso, Brasil, incluindo: praças públicas (n = 5), igrejas (n = 4), instituições de ensino (n = 3), unidades de saúde (n = 8), áreas abertas exibindo cobertura de amianto (n = 4), conjuntos residenciais domiciliares (n = 23), uma fábrica (n = 1) e um presídio (n = 1). Semeadura de suspensão de amostras em meio ágar niger (NSA), identificação fenotípica por provas bioquímicas e teste em meio de canavanina-glicina-azul de bromotimol, das colônias isoladas com pigmentação marrom escura. Foi também utilizada a técnica da reação em cadeia da polimerase com pares de iniciadores específicos para identificação de C. neoformans. As amostras foram coletadas de julho a dezembro de 2010. Cryptococcus neoformans foi isolado em oito (6,6%) de 122 amostras correspondendo a seis (12,2%) dos 49 sítios analisados. Cryptococcus neoformans associado a excretas de pombos ocorre em áreas de Cuiabá, predominando em residências nas amostras analisadas, constituindo fator de risco potencial para aquisição da doença tanto para indivíduos imunocomprometidos como imunocompetentes.SUMMARY Cryptococcosis is a severe systemic mycosis caused by two species of Cryptococcus that affect humans and animals: C. neoformans and C. gattii. Cosmopolitan and emergent, the mycosis results from the interaction between a susceptible host and the environment. The occurrence of C. neoformans was evaluated in 122 samples of dried pigeon excreta collected in 49 locations in the City of Cuiabá, State of Mato Grosso, Brazil, including public squares (n = 5), churches (n = 4), educational institutions (n = 3), health units (n = 8), open areas covered with asbestos (n = 4), residences (n = 23), factory (n = 1) and a prison (n = 1). Samples collected from July to December of 2010 were seeded on Niger seed agar (NSA). Dark brown colonies were identified by urease test, carbon source assimilation tests and canavanine-glycine-bromothymol blue medium. Polymerase chain reaction primer pairs specific for C. neoformans were also used for identification. Cryptococcus neoformans associated to pigeon excreta was isolated from eight (6.6%) samples corresponding to six (12.2%) locations. Cryptococcus neoformans was isolated from urban areas, predominantly in residences, constituting a risk of acquiring the disease by immunocompromised and immunocompetent individuals

Caffeine extends yeast lifespan by targeting TORC1

Dietary nutrient limitation (dietary restriction) is known to increase lifespan in a variety of organisms. Although the molecular events that couple dietary restriction to increased lifespan are not clear, studies of the model eukaryote Saccharomyces cerevisiae have implicated several nutrient-sensitive kinases, including the target of rapamycin complex 1 (TORC1), Sch9, protein kinase A (PKA) and Rim15. We have recently demonstrated that TORC1 activates Sch9 by direct phosphorylation. We now show that Sch9 inhibits Rim15 also by direct phosphorylation. Treatment of yeast cells with the specific TORC1 inhibitor rapamycin or caffeine releases Rim15 from TORC1-Sch9-mediated inhibition and consequently increases lifespan. This kinase cascade appears to have been evolutionarily conserved, suggesting that caffeine may extend lifespan in other eukaryotes, including man