Estudos sôbre óleos do fígado de cacão Desmobrânquios da família Sphyrnidae, Mir. Rib., gêneros Carcharias, Raf., Galeocerdo, Ranz., e Odontaspis, Shau

1. The author suggests a tecnique for the determination of vitamin A on shark liver oils in industrial plants. The advantages of using oly four ml. of reagent and of permitting a quickly rigorous reading by photoeletric cell, contribute to the possibility of the examination of a great number of samples daily; 2. It is described a survey on the vitamin A content of oils from shark livers, which has been made at the Finishing School Darcy Vargas, Marammaia Is., Rio de Janeiro State. The conclusions are the following: a) Male individuals have showed generally tendency for higher vitamin A pontency oils; b) The size of the fish does not interfere in the vitamin content of the oil (graphic 4); c) The data collected upon 3.085 individuals led to the conclusion that some species are richer in the reservated vitamin although it was possible to catch in the same specie fishes with widely variable potency in vitamin A. One fish belonging to the specie C. lamia produced the highest vitamin potency oil with 167.712 international units per gram; d) The fishing season appears to have no influence on the oils; e) The adventitous food seems to be the most important factor affecting the content of vitamin A of the shark-liver oils; 3. The presence and the quantity of vitamin D in those oils was investigated and two of the determinations are presented.

New or rare frogs from the Coastal Ranges of Brazil: eleutherodactylus venancioi n.sp., E. hoehnei n.sp. Holoaden bradei n.sp. e H. lüderwaldti Mir. Rib., 1920

Field-work in the sierras near the sea-board of south-eastern Brazil continues to yield new or rare frogs. Four more of these forms are presented here. Two of them, both new, are put into the genus Eleutherodactylus, to which they belong by their general habitat, morphology, and also by the osteological characters. They differs from the known regional species of this genus only by the wider and shorter disks of some of the digits and the more lanceolate build. The other two species belong to the very little known genus Holoaden, established by MIRANDA RIBEIRO in 1920. One of them is his type-species, H. lüderwaldti, which continues to be very rare. The other, H. bradei, is new. It seems endemic to the Upper Itatiaia and is very plentiful there.

Long-term miR-669a therapy alleviates chronic dilated cardiomyopathy in dystrophic mice.

BACKGROUND: Dilated cardiomyopathy (DCM) is a leading cause of chronic morbidity and mortality in muscular dystrophy (MD) patients. Current pharmacological treatments are not yet able to counteract chronic myocardial wastage, thus novel therapies are being intensely explored. MicroRNAs have been implicated as fine regulators of cardiomyopathic progression. Previously, miR-669a downregulation has been linked to the severe DCM progression displayed by Sgcb-null dystrophic mice. However, the impact of long-term overexpression of miR-669a on muscle structure and functionality of the dystrophic heart is yet unknown. METHODS AND RESULTS: Here, we demonstrate that intraventricular delivery of adeno-associated viral (AAV) vectors induces long-term (18 months) miR-669a overexpression and improves survival of Sgcb-null mice. Treated hearts display significant decrease in hypertrophic remodeling, fibrosis, and cardiomyocyte apoptosis. Moreover, miR-669a treatment increases sarcomere organization, reduces ventricular atrial natriuretic peptide (ANP) levels, and ameliorates gene/miRNA profile of DCM markers. Furthermore, long-term miR-669a overexpression significantly reduces adverse remodeling and enhances systolic fractional shortening of the left ventricle in treated dystrophic mice, without significant detrimental consequences on skeletal muscle wastage. CONCLUSIONS: Our findings provide the first evidence of long-term beneficial impact of AAV-mediated miRNA therapy in a transgenic model of severe, chronic MD-associated DCM.

Genomic, Epigenomic and Transcriptomic Molecular Characterization of Splenic Marginal Zone Lymphoma Reveals Recurrent Abnormalities in miR-182

Splenic marginal zone lymphoma (SMZL) is a low grade B-cell non-Hodgkin's lymphoma. The molecular pathology of this entity remains poorly understood. To characterise this lymphoma at the molecular level, we performed an integrated analysis of 1) genome wide genetic copy number alterations 2) gene expression profiles and 3) epigenetic DNA methylation profiles.We have previously shown that SMZL is characterised by recurrent alterations of chromosomes 7q, 6q, 3q, 9q and 18; however, gene resolution oligonucleotide array comparative genomic hybridisation did not reveal evidence of cryptic amplification or deletion in these regions. The most frequently lost 7q32 region contains a cluster of miRNAs. qRT-PCR revealed that three of these (miR-182/96/183) show underexpression in SMZL, and miR-182 is somatically mutated in >20% of cases of SMZL, as well as in >20% of cases of follicular lymphoma, and between 5-15% of cases of chronic lymphocytic leukaemia, MALT-lymphoma and hairy cell leukaemia. We conclude that miR-182 is a strong candidate novel tumour suppressor miRNA in lymphoma.The overall gene expression signature of SMZL was found to be strongly distinct fromthose of other lymphomas. Functional analysis of gene expression data revealed SMZL to be characterised by abnormalities in B-cell receptor signalling (especially through the CD19/21-PI3K/AKT pathway) and apoptotic pathways. In addition, genes involved in the response to viral infection appeared upregulated. SMZL shows a unique epigenetic profile, but analysis of differentially methylated genes showed few with methylation related transcriptional deregulation, suggesting that DNA methylation abnormalities are not a critical component of the SMZL malignant phenotype.

Regulation of monocyte functional heterogeneity by miR-146a and Relb.

Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6C(hi)/Ly-6C(lo)) and human (CD14(hi)/CD14(lo)CD16(+)) monocyte subsets. The single miRNA controlled the amplitude of the Ly-6C(hi) monocyte response during inflammatory challenge whereas it did not affect Ly-6C(lo) cells. miR-146a-mediated regulation was cell-intrinsic and depended on Relb, a member of the noncanonical NF-κB/Rel family, which we identified as a direct miR-146a target. These observations not only provide mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify targets for manipulating Ly-6C(hi) monocyte responses while sparing Ly-6Clo monocyte activity.

El llenguatge dels MIR en l'entrevista clínica: un aspecte del procés d'adaptació dels MIR autòctons i immigrats

Treball exploratori en què es presenta una metodologia d’anàlisi del llenguatge en la relació clínica a partir de la creació d’un Corpus, anomenat ClInt i que està a la lliure disposició de la comunitat investigadora. El corpus, comprèn 40 entrevistes enregistrades en àudio, transcrites ortogràficament i codificades de 4 MIR de primer anys de MFiC, 10 entrevistes per MIR en dos fases amb 10 mesos de diferència. En el treball descrivim les metodologies actualment disponibles per avaluar la competència comunicativa, presentem la població participant i utilitzant les eines que ofereix el corpus explorem l’evolució del vocabulari utilitzat pels MIR estudiats.

A miR-34a-SIRT6 axis in the squamous cell differentiation network.

Squamous cell carcinomas (SCCs) are highly heterogeneous tumours, resulting from deranged expression of genes involved in squamous cell differentiation. Here we report that microRNA-34a (miR-34a) functions as a novel node in the squamous cell differentiation network, with SIRT6 as a critical target. miR-34a expression increases with keratinocyte differentiation, while it is suppressed in skin and oral SCCs, SCC cell lines, and aberrantly differentiating primary human keratinocytes (HKCs). Expression of this miRNA is restored in SCC cells, in parallel with differentiation, by reversion of genomic DNA methylation or wild-type p53 expression. In normal HKCs, the pro-differentiation effects of increased p53 activity or UVB exposure are miR-34a-dependent, and increased miR-34a levels are sufficient to induce differentiation of these cells both in vitro and in vivo. SIRT6, a sirtuin family member not previously connected with miR-34a function, is a direct target of this miRNA in HKCs, and SIRT6 down-modulation is sufficient to reproduce the miR-34a pro-differentiation effects. The findings are of likely biological significance, as SIRT6 is oppositely expressed to miR-34a in normal keratinocytes and keratinocyte-derived tumours.

Mir-190b negatively contributes to the Trypanosoma cruzi- infected cell survival by repressing PTEN protein expression

Chagas disease, which is caused by the intracellular protozoanTrypanosoma cruzi, is a serious health problem in Latin America. The heart is one of the major organs affected by this parasitic infection. The pathogenesis of tissue remodelling, particularly regarding cardiomyocyte behaviour after parasite infection, and the molecular mechanisms that occur immediately following parasite entry into host cells are not yet completely understood. Previous studies have reported that the establishment of parasitism is connected to the activation of the phosphatidylinositol-3 kinase (PI3K), which controls important steps in cellular metabolism by regulating the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate. Particularly, the tumour suppressor PTEN is a negative regulator of PI3K signalling. However, mechanistic details of the modulatory activity of PTEN on Chagas disease have not been elucidated. To address this question, H9c2 cells were infected with T. cruzi Berenice 62 strain and the expression of a specific set of microRNAs (miRNAs) were investigated. Our cellular model demonstrated that miRNA-190b is correlated to the decrease of cellular viability rates by negatively modulating PTEN protein expression in T. cruzi-infected cells.

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

Regulación de la expresión del microRNA miR-21 por la proteína ZAP-70 en células de leucemia linfática crónica

La leucemia linfática crónica (LLC) está asociada a factores biológicos como la expresión de la proteína ZAP-70 y la expresión aberrante del miR-21. OBJETIVOS: Determinar la expresión de miR-21 en líneas celulares B y en células primarias de LLC y su asociación con la expresión de ZAP-70 en la LLC. MATERIAL Y MÉTODOS: Análisis de la expresión de miR-21 en la línea celular transfectada con ZAP-70 y en células de LLC. RESULTADOS: Se observó mayor expresión de miR-21 en las células con ZAP-70 tras estimulación del BCR y una correlación positiva entre la expresión de miR-21 y la de ZAP-70.

Post-axial polydactyly type A2, overgrowth and autistic traits associated with a chromosome 13q31.3 microduplication encompassing miR-17-92 and GPC5.

Genomic rearrangements at chromosome 13q31.3q32.1 have been associated with digital anomalies, dysmorphic features, and variable degree of mental disability. Microdeletions leading to haploinsufficiency of miR17∼92, a cluster of micro RNA genes closely linked to GPC5 in both mouse and human genomes, has recently been associated with digital anomalies in the Feingold like syndrome. Here, we report on a boy with familial dominant post-axial polydactyly (PAP) type A, overgrowth, significant facial dysmorphisms and autistic traits who carries the smallest germline microduplication known so far in that region. The microduplication encompasses the whole miR17∼92 cluster and the first 5 exons of GPC5. This report supports the newly recognized role of miR17∼92 gene dosage in digital developmental anomalies, and suggests a possible role of GPC5 in growth regulation and in cognitive development.

'sît ich die nôt an mir weiz'. Zur narrativen Konfiguration des lyrischen 'paradoxe amoureux' im "Mauritius von Craûn"

Der am ehesten um 1200 entstandene ,Mauritius von Craûn' gilt als Forschungsproblem. Als gemeinsamen Nenner der kontroversen Zugänge zum Text konstatiert der Aufsatz das Bemühen um eine Verbindung der rätselhaften Erzählung mit einem durch die historische Distanz verlorenen oder verwischten Sinnzusammenhang über einen textexternen missing link. Demgegenüber wird ein themen- und handlungsanalytischer Zugriff vorgeschlagen: Thema der Erzählung ist die im 12. Jahrhundert vorrangig in der Lyrik entwickelte strukturelle Figur der Hohen Minne, die ihre Ästhetik aus einem Paradox gewinnt: Die Möglichkeitsbedingung dieser in beständigem Werben bestehenden Liebe, die niemals erfüllt werden darf, ist ihre Unmöglichkeit. Seine ideelle Füllung erhält das Modell durch eine darin vernetzte Ordnung höfischer Werte wie stæte, triuwe, milte oder mâze. Diese Werte, so die These, ,,erzählt" die Handlung des ,Mauritius': Hier wird nicht nur der Versuch unternommen, lyrische Struktur in narrative Struktur zu verwandeln, sondern auch der, eine ins lyrische Modell eingebettete Ordnung ethischen Wissens zu narrativieren. Einzelne Figurenhandlungen erscheinen aus dieser Perspektive weniger als Bestandteile eines inhaltlichen Entwurfs mit dem Anspruch übergreifender Stimmmigkeit und dem Fluchtpunkt eines Deutungsangebots, sondern als Ausdruck verschieden graduierter Negierungen oder Positivierungen eines bestimmtes Wertes. Hierfür sprechen auch die konstanten Über- oder Unterzeichnungen der Figurenhandlungen, die als markantestes Merkmal der narrativen Faktur des Textes beschrieben werden. Die Mikroanalyse einer einzelnen Szene zeigt ferner, wie die Dichotomie von Statik und Dynamik, die schon dem lyrischen Entwurf der Hohen Minne eingeschrieben ist und die durch die Narrativierung des lyrischen Konzepts im ,Mauritius' zunehmend virulent wird, in Sequenzen aufeinanderfolgender Doppelungen von Bewegung und Zustand auserzählt wird. Insgesamt lässt sich der ,Mauritius' als Erprobung von Verfahren verstehen, eine idealisierte höfische Welt in Analogie zum lyrischen Modus auch im narrativen Modus zu literarisieren: als ein Stück Erzählkasuistik.