Saturation mutagenesis of the beta subunit of the human granulocyte-macrophage colony-stimulating factor receptor shows clustering of constitutive mutations, activation of ERK MAP kinase and STAT pathways, and differential beta subunit tyrosine phosphoryl

The high-affinity receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-3), and IL-5 are heterodimeric complexes consisting of cytokine-specific alpha subunits and a common signal-transducing beta subunit (h beta c). We have previously demonstrated the oncogenic potential of this group of receptors by identifying constitutively activating point mutations in the extracellular and transmembrane domains of h beta c. We report here a comprehensive screen of the entire h beta c molecule that has led to the identification of additional constitutive point mutations by virtue of their ability to confer factor independence on murine FDC-P1 cells. These mutations were clustered exclusively in a central region of h beta c that encompasses the extracellular membrane-proximal domain, transmembrane domain, and membrane-proximal region of the cytoplasmic domain. Interestingly, most h beta c mutants exhibited cell type-specific constitutive activity, with only two transmembrane domain mutants able to confer factor independence on both murine FDC-P1 and BAF-B03 cells. Examination of the biochemical properties of these mutants in FDC-P1 cells indicated that MAP kinase (ERK1/2), STAT, and JAK2 signaling molecules were constitutively activated. In contrast, only some of the mutant beta subunits were constitutively tyrosine phosphorylated. Taken together; these results highlight key regions involved in h beta c activation, dissociate h beta c tyrosine phosphorylation from MAP kinase and STAT activation, and suggest the involvement of distinct mechanisms by which proliferative signals can be generated by h beta c. (C) 1998 by The American Society of Hematology.

ViDi Stat

A tese desenvolvida tem como foco fornecer os meios necessários para extrair conhecimento contidos no histórico académico da instituição transformando a informação em algo simples e de fácil leitura para qualquer utilizador. Com o progresso da sociedade, as escolas recebem milhares de alunos todos os anos que terão de ser orientados e monitorizados pelos dirigentes das instituições académicas de forma a garantir programas eficientes e adequados para o progresso educacional de todos os alunos. Atribuir a um docente a responsabilidade de actuar segundo o historial académico dos seus alunos não é plausível uma vez que um aluno consegue produzir milhares de registos para análise. O paradigma de mineração de dados na educação surge com a necessidade de otimizar os recursos disponíveis expondo conclusões que não se encontram visiveis sem uma análise acentuada e cuidada. Este paradigma expõe de forma clara e sucinta os dados estatísticos analisados por computador oferecendo a possibilidade de melhorar as lacunas na qualidade de ensino das instituições. Esta dissertação detalha o desenvolvimento de uma ferramente de inteligência de negócio capaz de, através de mineração de dados, analisar e apresentar conclusões pertinentes de forma legível ao utilizador.

ViDi Stat

A tese desenvolvida tem como foco fornecer os meios necessários para extrair conhecimento contidos no histórico académico da instituição transformando a informação em algo simples e de fácil leitura para qualquer utilizador. Com o progresso da sociedade, as escolas recebem milhares de alunos todos os anos que terão de ser orientados e monitorizados pelos dirigentes das instituições académicas de forma a garantir programas eficientes e adequados para o progresso educacional de todos os alunos. Atribuir a um docente a responsabilidade de actuar segundo o historial académico dos seus alunos não é plausível uma vez que um aluno consegue produzir milhares de registos para análise. O paradigma de mineração de dados na educação surge com a necessidade de otimizar os recursos disponíveis expondo conclusões que não se encontram visiveis sem uma análise acentuada e cuidada. Este paradigma expõe de forma clara e sucinta os dados estatísticos analisados por computador oferecendo a possibilidade de melhorar as lacunas na qualidade de ensino das instituições. Esta dissertação detalha o desenvolvimento de uma ferramente de inteligência de negócio capaz de, através de mineração de dados, analisar e apresentar conclusões pertinentes de forma legível ao utilizador.

Regulation der IL-6-induzierten Jak/STAT Signaltransduktion : Reduktion der SOCS3 Expression durch Glukokortikoide und systembiologische Analyse der Funktion von SHP2

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2012

Revision of the subfamily Rogenhoferinae stat. nov. (Diptera, Cuterebridae)

The subfamily Rogenhoferinae stat. nov. (Diptera, Cuterebridae) is revised. Two genera are recognized: Rogenhofera Brauer (Type-species, trigonophora Brauer) and Andinocutereba Guimarães (Type-species, fassleri Guimarães). Five species are recorded in Rogenhofera, one R. lopesi is described as new. Key to species, illustrations and distribution are presented.

DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites.

STAT transcription factors are expressed in many cell types and bind to similar sequences. However, different STAT gene knock-outs show very distinct phenotypes. To determine whether differences between the binding specificities of STAT proteins account for these effects, we compared the sequences bound by STAT1, STAT5A, STAT5B, and STAT6. One sequence set was selected from random oligonucleotides by recombinant STAT1, STAT5A, or STAT6. For another set including many weak binding sites, we quantified the relative affinities to STAT1, STAT5A, STAT5B, and STAT6. We compared the results to the binding sites in natural STAT target genes identified by others. The experiments confirmed the similar specificity of different STAT proteins. Detailed analysis indicated that STAT5A specificity is more similar to that of STAT6 than that of STAT1, as expected from the evolutionary relationships. The preference of STAT6 for sites in which the half-palindromes (TTC) are separated by four nucleotides (N(4)) was confirmed, but analysis of weak binding sites showed that STAT6 binds fairly well to N(3) sites. As previously reported, STAT1 and STAT5 prefer N(3) sites; however, STAT5A, but not STAT1, weakly binds N(4) sites. None of the STATs bound to half-palindromes. There were no specificity differences between STAT5A and STAT5B.

SOCS-1 protein prevents Janus Kinase/STAT-dependent inhibition of beta cell insulin gene transcription and secretion in response to interferon-gamma.

In the pathogenesis of type I diabetes mellitus, activated leukocytes infiltrate pancreatic islets and induce beta cell dysfunction and destruction. Interferon (IFN)-gamma, tumor necrosis factor-alpha and interleukin (IL)-1 beta play important, although not completely defined, roles in these mechanisms. Here, using the highly differentiated beta Tc-Tet insulin-secreting cell line, we showed that IFN-gamma dose- and time-dependently suppressed insulin synthesis and glucose-stimulated secretion. As described previously IFN-gamma, in combination with IL-1 beta, also induces inducible NO synthase expression and apoptosis (Dupraz, P., Cottet, S., Hamburger, F., Dolci, W., Felley-Bosco, E., and Thorens, B. (2000) J. Biol. Chem. 275, 37672--37678). To assess the role of the Janus kinase/signal transducer and activator of transcription (STAT) pathway in IFN-gamma intracellular signaling, we stably overexpressed SOCS-1 (suppressor of cytokine signaling-1) in the beta cell line. We demonstrated that SOCS-1 suppressed cytokine-induced STAT-1 phosphorylation and increased cellular accumulation. This was accompanied by a suppression of the effect of IFN-gamma on: (i) reduction in insulin promoter-luciferase reporter gene transcription, (ii) decrease in insulin mRNA and peptide content, and (iii) suppression of glucose-stimulated insulin secretion. Furthermore, SOCS-1 also suppressed the cellular effects that require the combined presence of IL-1 beta and IFN-gamma: induction of nitric oxide production and apoptosis. Together our data demonstrate that IFN-gamma is responsible for the cytokine-induced defect in insulin gene expression and secretion and that this effect can be completely blocked by constitutive inhibition of the Janus kinase/STAT pathway.

Revisão de Ceyxia Girault, stat. rev. (Hymenoptera, Chalcididae, Brachymeriini)

O gênero Ceyxia Girault é revalidado e 27 espécies são combinadas a ele. Sete espécies previamente descritas são diagnosticadas (ou redescritas) e discutidas, e 20 espécies novas são descritas. Ceyxia flaviscapus Girault, 1911 and C. ventrispinosa Girault, 1911 stat. rev. foram originalmente combinadas com Ceyxia e as seguintes são combinações novas: C. belfragei (Crawford, 1910) comb. nov., stat. rev.; C. concitator (Walker, 1862) comb. nov.; C. decreta (Walker, 1862) comb. nov.; C. dorsalis (Walker, 1861) comb. nov.; e C. villosa (Olivier, 1790) comb. nov. Ceyxia paraguayensis Girault, 1911 é consyiderada sinônimo júnior de Ceyxia flaviscapus Girault, 1911. As novas espécies são: C. acutigaster sp. nov.; C. amazonica sp. nov.; C. atuberculata sp. nov.; C. bellissima sp. nov.; C. dentiformis sp. nov.; C. diminuta sp. nov.; C. fusidentata sp. nov.; C. gibbosa sp. nov.; C. laminata sp. nov.; C. laticlipeata sp. nov.; C. latilabra sp. nov.; C. longiarticulata sp. nov.; C. longiscutellaris sp. nov.; C. longispina sp. nov.; C. nigropetiolata sp. nov.; C. paraensis sp. nov.; C. parvidentata sp. nov.; C. perparva sp. nov.; C. pseudovillosa sp. nov.; e C. tibiodilatata sp. nov. Dados sobre a associação com hospedeiros são apresentados para algumas espécies do gênero. Uma chave para as espécies do gênero é incluída.

The genus Lycoderides Sakakibara, stat. nov., its composition and descriptions of new species (Hemiptera, Membracidae, Stegaspidinae)

The genus Lycoderides Sakakibara, stat. nov. , its composition and descriptions of new species (Hemiptera, Membracidae, Stegaspidinae).The subgenus Lycoderes (Lycoderides) Sakakibara, 1972 is raised to the genus category - Lycoderides stat. nov.. - : and it now includes: Lycoderides amazonicus (Sakakibara, 1991), comb. nov. , Lycoderides brevilobus (Sakakibara, 1972), comb. nov. , Lycoderides burmeisteri (Fairmaire, 1846), comb. nov. , Lycoderides cultratus (Sakakibara, 1991), comb. nov. , Lycoderides fernandezi (Strümpel, 1988), comb. nov. , Lycoderides fuscus (Amyot & Serville, 1843), comb. nov. , Lycoderides gradatus (Sakakibara, 1972), comb. nov. , Lycoderides hippocampus (Fabricius, 1803), comb. nov. , Lycoderides luteus (Funkhouser, 1940), comb. nov. , Lycoderides marginalis (Walker, 1851), comb. nov. , Lycoderides nathanieli (Cryan, 1999), comb. nov. , Lycoderides obtusus (Sakakibara, 1991), comb. nov. , Lycoderides pennyi (Sakakibara, 1991), comb. nov. , Lycoderides phasianus (Fowler, 1896), comb. nov. (= Enchenopa minamen Buckton, 1901,SYN. NOV: ), Lycoderides protensus (Sakakibara, 1991), comb. nov. , Lycoderides serraticornis (Fowler, 1896), comb. nov. , and Lycoderides strumpeli (Sakakibara, 1991), comb. nov. The following new species are described: Lycoderides abditus, sp. nov. , Lycoderides brulei,SP. NOV. (: both from French Guiana), Lycoderides capixaba, sp. nov. (from Brazil, Espírito Santo), Lycoderides cavichiolii, sp. nov. (from Brazil, Rio de Janeiro), Lycoderides meloi, sp. nov. (from Brazil, Bahia), and Lycoderides oliviae, sp. nov. (from Brazil, Minas Gerais). Other nomenclatural change: Stegaspis bracteata (Fabricius, 1787) = Lycoderes capitata Buckton, 1903, syn. nov. New records of geographical distribution and a key to the species are provided.

A pilot assessment of alpha-stat vs pH-stat arterial blood gas analysis after cardiac arrest.

PURPOSE: Resuscitated cardiac arrest (CA) patients typically receive therapeutic hypothermia, but arterial blood gases (ABGs) are often assessed after adjustment to 37°C (alpha-stat) instead of actual body temperature (pH-stat). We sought to compare alpha-stat and pH-stat assessment of Pao2 and Paco2 in such patients. MATERIALS AND METHODS: Using ABG data obtained during the first 24 hours of intensive care unit admission, we determined the impact of measured alpha vs calculated pH-stat on Pao2 and Paco2 on patient classification and outcomes for CA patients. RESULTS: We assessed 1013 ABGs from 120 CA patients with a median age of patients 66 years (interquartile range, 50-76). Median alpha-stat Pao2 changed from 122 (95-156) to 107 (82-143) mm Hg with pH-stat and median Paco2 from 39 (34-46) to 35 (30-41) mm Hg (both P < .001). Using the categories of hyperoxemia, normoxemia, and hypoxemia, pH-stat estimation of Pao2 reclassified approximately 20% of patients. Using the categories of hypercapnia, normocapnia, and hypocapnia, pH stat estimation of Paco2 reclassified approximately 40% of patients. The mortality of patients in different Pao2 and Paco2 categories was similar for pH-stat and alpha-stat. CONCLUSIONS: Using the pH-stat method, fewer resuscitated CA patients admitted to intensive care unit were classified as hyperoxemic or hypercapnic compared with alpha-stat. These findings suggest an impact of ABG assessment methodology on Pao2, Paco2, and patient classification but not on associated outcomes.

Reactivity of silicate liming materials from Northern Europe assessed by Soil Incubation and two pH Stat methods

Selostus: Pohjois-Euroopan silikaattisten kalkitusaineiden reaktiivisuus astiakoemenetelmällä ja kahdella pH-staattisella menetelmällä arvioituna

Contribucion al estudio biotaxonomico de Thymus loscosii Willk. y Thymus fontqueri (Jalas) Molero & Rovira, stat. nov.

Después de estudiar comparativamente la morfología, corología, ecología, número cromosomático y aceite esencial de los táxones Thymus loscosii Willk. y Thymus loscosii Willk. subsp. fontqueri Jalas, se concluye, de forma razonada, que el status más adecuado para este último es el de especie, combinándose de nuevo cpmo Thymus fontqueri (Jalas) Molero & Rovira; también se propone su inclusión en la sección Serpyllum (Miller) Bentham. En el estudio del aceite esencial de ambos tomillos por CGL e IR se han identificado 14 de sus componentes, destacando el p-citral, mirceno, cineol y alcanfor como mayoritarios. El cromatograma que presentan es muy parecido, pudiéndose atribuir a un quimótipo común P-citral (y otro compuesto no identificado). Entre los componentes la oscilación es máxima para el mirceno, claramente predominante en el T. fontqueri.

Vitamin D Receptor and Jak-STAT Signaling Crosstalk Results in Calcitriol-Mediated Increase of Hepatocellular Response to IFN-α.

Recent clinical research suggests a role for vitamin D in the response to IFN-α-based therapy of chronic hepatitis C. Therefore, we aimed to explore the underlying mechanisms in vitro. Huh-7.5 cells harboring subgenomic hepatitis C virus (HCV) replicons or infected with cell culture-derived HCV were exposed to bioactive 1,25-dihydroxyvitamin D3 (calcitriol) with or without IFN-α. In these experiments, calcitriol alone had no effect on the HCV life cycle. However, calcitriol enhanced the inhibitory effect of IFN-α on HCV replication. This effect was based on a calcitriol-mediated increase of IFN-α-induced gene expression. Further mechanistic studies revealed a constitutive inhibitory interaction between the inactive vitamin D receptor (VDR) and Stat1, which was released upon stimulation with calcitriol and IFN-α. As a consequence, IFN-α-induced binding of phosphorylated Stat1 to its DNA target sequences was enhanced by calcitriol. Importantly, and in line with these observations, silencing of the VDR resulted in an enhanced hepatocellular response to IFN-α. Our findings identify the VDR as a novel suppressor of IFN-α-induced signaling through the Jak-STAT pathway.

Short communication. SNP analyses of the 5HT1R and STAT genes in Pacific white shrimp, Litopenaeus vannamei

La industria de la producción de camarón es una de las industrias acuícolas que se encuentra en más crecimiento en la actualidad. Los estudios para encontrar marcadores genéticos son muy efectivos para la mejora de sus propiedades y de gran interés para los productores de camarón. En este trabajo se utilizaron seis individuos de una población de Litopenaeus vannamei, donde se encontraron cuatro polimorfismos de nucleótido único (SNPs) en el gen 5HT1R (5-hidroxitriptamina receptor1) y un SNP en el gen STAT (transductor de señal y activador de la transcripción). Sin embargo, el polimorfismo en el gen STAT resultó ser homocigoto en una población diferente utilizada para análisis de asociación. Los presentes análisis revelaron que el alelo C, en dos polimorfismos SNP (C109T y C395G) del gen 5HT1R, tiende a estar asociado con el aumento del peso corporal. Consideramos que hay necesidad de hacer nuevos estudios utilizando una muestra más amplia y diversa de la población en cuestión.