94 research outputs found

    Akt Is S-Palmitoylated: A New Layer of Regulation for Akt

    Get PDF
    The protein kinase Akt/PKB participates in a great variety of processes, including translation, cell proliferation and survival, as well as malignant transformation and viral infection. In the last few years, novel Akt posttranslational modifications have been found. However, how these modification patterns affect Akt subcellular localization, target specificity and, in general, function is not thoroughly understood. Here, we postulate and experimentally demonstrate by acyl-biotin exchange (ABE) assay and (3)H-palmitate metabolic labeling that Akt is S-palmitoylated, a modification related to protein sorting throughout subcellular membranes. Mutating cysteine 344 into serine blocked Akt S-palmitoylation and diminished its phosphorylation at two key sites, T308 and T450. Particularly, we show that palmitoylation-deficient Akt increases its recruitment to cytoplasmic structures that colocalize with lysosomes, a process stimulated during autophagy. Finally, we found that cysteine 344 in Akt1 is important for proper its function, since Akt1-C344S was unable to support adipocyte cell differentiation in vitro. These results add an unexpected new layer to the already complex Akt molecular code, improving our understanding of cell decision-making mechanisms such as cell survival, differentiation and death

    Molecular structure of the largemouth bass (Micropterus salmoides) Myf5 gene and its effect on skeletal muscle growth

    Get PDF
    Myogenic Regulatory Factors (MRFs), a family of basic helix-loop-helix (bHLH) transcription factors, play important roles in regulating skeletal muscle development and growth. Myf5, the primary factor of MRFs, initiates myogenesis. Its expression pattern during somitomyogenesis in some fish has been revealed. To further study its effect on fish muscle during postembryonic growth, characterization and function analysis of myf5 cDNA were carried out in largemouth bass. The 1,093 bp cDNA sequence was identified by RT-PCR and 3′RACE, then the ORF of Myf5 cDNA was cloned into the expression vector pcDNA3.1(−)/mycHisB. The recombinant plasmid pcDNA3.1(−)/mycHisB-Myf5 was injected into the dorsal muscle of tilapias. RT-PCR and histochemical results showed that the exogenous gene was transcribed and translated in vivo. Its effect on muscle growth focused on myofiber hypertrophy in white muscle 60 days post injection. This indicated that overexpression of Myf5 can promote myogenesis during the fish muscle postembryonic growth period

    Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.)

    Get PDF
    Hyperplasia and hypertrophy are the two mechanisms by which muscle develops and grows. We study these two mechanisms, during the early development of white muscle in Sparus aurata, by means of histology and the expression of structural and regulatory genes. A clear stage of stratified hyperplasia was identified early in the development of gilthead sea bream but ceased by 35 dph when hypertrophy took over. Mosaic recruitment of new white fibers began as soon as 60 dph. The genes mlc2a and mlc2b were expressed at various levels during the main phases of hyperplasia and hypertrophy. The genes myog and mlc2a were significantly up-regulated during the intensive stratified formation of new fibers and their expression was significantly correlated. Expression of mstn1 and igf1 increased at 35 dph, appeared to regulate the hyperplasia-to-hypertrophy transition, and may have stimulated the expression of mlc2a, mlc2b and col1a1 at the onset of mosaic hyperplasia. The up-regulation of mstn1 at transitional phases in muscle development indicates a dual regulatory role of myostatin in fish larval muscle growth

    Language production impairments in patients with a first episode of psychosis

    Get PDF

    A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

    Get PDF
    Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

    Gut glycoconjugates in Sparus aurata L. (Pisces, Teleostei). A comparative histochemical study in larval and adult ages

    Get PDF
    This study examined the gut of the euryaline fish Sparus aurata, from the pharynx to the rectum. The specimens were collected from adult animals, both sexes, and several larval and juvenile stages, from 4 to 135 days of age. Histochemical methods to distinguish neutral and acidic glycoconjugates, as well as specific techniques to identify acidic glycoconjugates which contained 0-acylated sialic acids were used. The presence and distribution of sugar residues in the oligosaccharide side chain of glycoconjugates were investigated with the use of biotinylated lectins. The pharynx and oesophagus of adult fishes showed the presence of abundant secretory cells which synthesized a large quantity of neutral, as well as sulphated and sialylated glycoconjugates, with different cellular combinations of them in the proximal and distal tract. This may be related to the complex functions carried out by this end of the gut in a marine euryaline fish. Epithelia1 secretory cells were found in the developing oesophagus during larval life (14 days) earlier than in the stomach and intestine (34 days). The simple columnar epithelium that lined the gastric mucosa of adult fish synthesized a mixture of neutral and acidic glycoconjugates, whereas during larval life it was shown to contain neutral glycoconjugates only. The intestinal goblet cells were shown to secrete both neutral and acidic glycoconjugates, especially sulphated forms. The adherent mucus gel of the gastric and intestinal mucosa contained many sugar residues, as revealed by lectin histochemistry. This work clearly demonstrates that the quality of gut mucosubstances varies in different ages and in regions of the fish alimentary canal. This is possibly caused by changes in environmental conditions and may in turn sustain functional alterations of the digestive apparatus

    L\u2019epizoozia del 1783-84 nel Veneto Dominio. Giuseppe Orus e le proteste di un chiacchierone

    No full text
    Attraverso il carteggio intercorso tra Luigi Ballarini, agente e procuratore della nobile famiglia Dolfin, e le autorit\ue0 veneziane preposte alla Salute pubblica, si ricostituiscono gli eventi che portarono nel 1783 al propagarsi di una grave epizoozia in terra veneta, veicolata da bovini destinati al macello, provenienti dalla Dalmazia. Infatti gli appaltatori delle carni, per non subire danni economici, anzich\ue9 mettere in quarantena i bovini li immisero sul mercato disperdendoli su un vasto territorio. Ne risulta un vivace spaccato di vita quotidiana dove gli interessi dei mercanti si intrecciano con i non sempre tempestivi provvedimenti delle pubbliche autorit\ue0, l\u2019ottusit\ue0 dei villici, l\u2019impotenza della medicina di allora che contro i morbi epidemici poteva solo opporre le ferree misure di prevenzione indicate dal Lancisi, non certo efficaci metodi curativi. Di qui il risentimento e l\u2019animosa ostilit\ue0 del Ballarini verso il professore di veterinaria Giuseppe Orus, fondatore del Collegium Zooiatricum patavinum che, chiamato in causa dalle autorit\ue0 al suo rientro a Padova dalla natia Parma, dove aveva trascorso le vacanze estive, non essendo stato debitamente informato dell\u2019avvenuta dispersione dei bovini infetti, sottovalut\uf2 in un primo tempo l\u2019entit\ue0 del contagio, prescrivendo i rimedi allora in voga che naturalmente non potevano sortire gli effetti desiderati
    corecore