The NC2 repressor is dispensable in yeast mutated for the Sin4p component of the holoenzyme and plays roles similar to Mot1p in vivo

NC2 (Dr1/DRAP1) and Mot1p are global repressors of transcription that have been isolated in both Saccharomyces cerevisiae and humans. NC2 is a dimeric histone-fold complex that represses RNA polymerase II transcription through binding to TBP and inhibition of TFIIA and TFIIB. Mot1p is an ATPase that removes DNA-bound TBP upon ATP hydrolysis. In this work, we studied the core promoter specificity of NC2 in vivo using a strain that carries mutated NC2beta activity. We show that NC2, like Mot1p, is required for transcription of the HIS3 and HIS4 TATA-less core promoters. Furthermore, whereas neither Mot1p nor NC2 appear to function as repressors of the HIS3 gene in cells growing exponentially in glucose, we find that both are required for repression of the HIS3 TATA promoter when cells go through the diauxic shift. Thus, the activity of these factors is similarly regulated depending upon the physiological conditions, and it appears that core promoters activated or repressed by them in vivo might be distinguishable by whether or not they contain a canonical TATA sequence. Finally, although NC2 is an essential factor for yeast viability, we isolated a mutation in a non-essential component of the holoenzyme, Sin4p, that bypasses the requirement for NC2

Saccharomyces cerevisiae Ccr4–Not complex contributes to the control of Msn2p-dependent transcription by the Ras/cAMP pathway

The Ccr4–Not complex is a global regulator of transcription that affects genes positively and negatively and is thought to modulate the activity of TFIID. In the present work, we provide evidence that the Ccr4–Not complex may contribute to transcriptional regulation by the Ras/cAMP pathway. Several observations support this model. First, Msn2/4p-dependent transcription, which is known to be under negative control of cAMP-dependent protein kinase (PKA), is derepressed in all ccr4–not mutants. This phenotype is paralleled by specific post-translational modification defects of Msn2p in ccr4–not mutants relative to wild-type cells. Secondly, mutations in various NOT genes result in a synthetic temperature-sensitive growth defect when combined with mutations that compromise cells for PKA activity and at least partially suppress the effects of both a dominant-active RAS2Val-19 allele and loss of Rim15p. Thirdly, Not3p and Not5p, which are modified and subsequently degraded by stress signals that also lead to increased Msn2/4p-dependent activity, show a specific twohybrid interaction with Tpk2p. Together, our results suggest that the Ccr4–Not complex may function as an effector of the Ras/cAMP pathway that contributes to repress basal, stress- and starvation-induced transcription by Msn2/4p

TIA1 Loss Exacerbates Fatty Liver Disease but Exerts a Dual Role in Hepatocarcinogenesis.

Alterations in specific RNA-binding protein expression/activity importantly contribute to the development of fatty liver disease (FLD) and hepatocellular carcinoma (HCC). In particular, adenylate-uridylate-rich element binding proteins (AUBPs) were reported to control the post-transcriptional regulation of genes involved in both metabolic and cancerous processes. Herein, we investigated the pathophysiological functions of the AUBP, T-cell-restricted intracellular antigen-1 (TIA1) in the development of FLD and HCC. Analysis of TIA1 expression in mouse and human models of FLD and HCC indicated that TIA1 is downregulated in human HCC. In vivo silencing of TIA1 using AAV8-delivered shRNAs in mice worsens hepatic steatosis and fibrosis induced by a methionine and choline-deficient diet and increases the hepatic tumor burden in liver-specific PTEN knockout (LPTENKO) mice. In contrast, our in vitro data indicated that TIA1 expression promoted proliferation and migration in HCC cell lines, thus suggesting a dual and context-dependent role for TIA1 in tumor initiation versus progression. Consistent with a dual function of TIA1 in tumorigenesis, translatome analysis revealed that TIA1 appears to control the expression of both pro- and anti-tumorigenic factors in hepatic cancer cells. This duality of TIA1's function in hepatocarcinogenesis calls for cautiousness when considering TIA1 as a therapeutic target or biomarker in HCC

Crescimento relativo do camar\ue3o canela Macrobrachium amazonicum (Heller) (Crustacea, Decapoda, Palaemonidae) em viveiros

<abstract language="eng">Some morphometric relationships in Macrobrachium amazonicum (Heller, 1862) reared in earthen ponds were studied. A total of 239 individuals were collected, sexed and sorted to juvenile or adult. Total length (Lt), post-orbital length (Lpo), carapace length (Lcp) and queliped length (Lql) were measured. The relationships Lt/Lpo, Lpo/Lcp and Lt/Lcp are the same for juveniles, males and females, indicating unchanged growth pattern during post-larval ontogenetic development. While Lt/Lpo showed isometric growth, Lpo/Lcp and Lt/Lcp showed negative allometry. On the other hand, for the Lql/Lcp relationship, juveniles showed isometric growth, females slight positive allometry and males a strong positive allometry. It suggests that the importance of chelipeds may be different in these groups. Quelipeds play important role on food capture and on agonistic, social and reproductive behavior. Therefore, inter and intraspecific interactions may change during prawn growth, even after morphologica

Simultaneous expression and regulation of G‐CSF and IL‐6 mRNA in adherent human monocytes and fibroblasts

The regulation of granulocyte-colony stimulating factor (G-CSF) and interleukin-6 (IL-6) mRNA was studied in human adherent monocytes in response to the protein kinase C activator, oleolyl-acetylglycerol (OAG), the calcium-ionophore A23187 and the cyclic AMP elevating agents, dibutyryl c-AMP (DBcAMP), cholera toxin and isobutyl-methylxanthine (IBMX). G-CSF and IL-6 transcripts were simultaneously expressed in response to OAG, A23187, DBcAMP, IBMX and cholera toxin. However, the time course demonstrated a difference; a rapid induction by OAG and A23187 and a delayed pattern by cAMP elevating agents. In addition it appeared that the induction of CSFs by DBcAMP was independent of the adherence procedure or the presence of fetal bovine serum but could be counteracted by the simultaneous addition of H8, an inhibitor of the cAMP dependent kinases. Finally, experiments were performed to study in how far comparable mechanisms operate in other cell types. Human fetal lung fibroblasts were stimulated with A23187, DBcAMP and OAG. All these agents induced simultaneous expression of G-CSF and IL-6 mRNA and secretion of proteins, indicating that different signalling pathways exist in both cell types which regulate the expression of both genes