GENCODE: producing a reference annotation for ENCODE

Background: The GENCODE consortium was formed to identify and map all protein-coding genes within the ENCODE regions. This was achieved by a combination of initial manualannotation by the HAVANA team, experimental validation by the GENCODE consortium and a refinement of the annotation based on these experimental results.Results: The GENCODE gene features are divided into eight different categories of which onlythe first two (known and novel coding sequence) are confidently predicted to be protein-codinggenes. 5’ rapid amplification of cDNA ends (RACE) and RT-PCR were used to experimentallyverify the initial annotation. Of the 420 coding loci tested, 229 RACE products have beensequenced. They supported 5’ extensions of 30 loci and new splice variants in 50 loci. In addition,46 loci without evidence for a coding sequence were validated, consisting of 31 novel and 15putative transcripts. We assessed the comprehensiveness of the GENCODE annotation byattempting to validate all the predicted exon boundaries outside the GENCODE annotation. Outof 1,215 tested in a subset of the ENCODE regions, 14 novel exon pairs were validated, only twoof them in intergenic regions.Conclusions: In total, 487 loci, of which 434 are coding, have been annotated as part of theGENCODE reference set available from the UCSC browser. Comparison of GENCODEannotation with RefSeq and ENSEMBL show only 40% of GENCODE exons are contained withinthe two sets, which is a reflection of the high number of alternative splice forms with uniqueexons annotated. Over 50% of coding loci have been experimentally verified by 5’ RACE forEGASP and the GENCODE collaboration is continuing to refine its annotation of 1% humangenome with the aid of experimental validation.

Histone deacetylase inhibitors repress macrophage migration inhibitory factor (MIF) expression by targeting MIF gene transcription through a local chromatin deacetylation.

The cytokine macrophage migration inhibitory factor plays a central role in inflammation, cell proliferation and tumorigenesis. Moreover, macrophage migration inhibitory factor levels correlate with tumor aggressiveness and metastatic potential. Histone deacetylase inhibitors are potent antitumor agents recently introduced in the clinic. Therefore, we hypothesized that macrophage migration inhibitory factor would represent a target of histone deacetylase inhibitors. Confirming our hypothesis, we report that histone deacetylase inhibitors of various chemical classes strongly inhibited macrophage migration inhibitory factor expression in a broad range of cell lines, in primary cells and in vivo. Nuclear run on, transient transfection with macrophage migration inhibitory factor promoter reporter constructs and transduction with macrophage migration inhibitory factor expressing adenovirus demonstrated that trichostatin A (a prototypical histone deacetylase inhibitor) inhibited endogenous, but not episomal, MIF gene transcription. Interestingly, trichostatin A induced a local and specific deacetylation of macrophage migration inhibitory factor promoter-associated H3 and H4 histones which did not affect chromatin accessibility but was associated with an impaired recruitment of RNA polymerase II and Sp1 and CREB transcription factors required for basal MIF gene transcription. Altogether, this study describes a new molecular mechanism by which histone deacetylase inhibitors inhibit MIF gene expression, and suggests that macrophage migration inhibitory factor inhibition by histone deacetylase inhibitors may contribute to the antitumorigenic effects of histone deacetylase inhibitors.

¶ COPIE DER BRIEVEN || VAN DEN GROOTẽ TURCK ghescreuẽ aẽ mijn Heere dẽ || grootẽ meestere van Rodes omtrẽt sint Ians misse || laetst ledẽ anno. M. ccccc. xxij. En oec eẽ Epistel vã || d' stadt vã Rodes / aẽ dat heylich Catholicke geloue. || Rodes. — [A la fin] : ¶ Dese Copie es vandẽ walsche ghetranslateert in || onsen tale Eñ is eerst gecõponeert par songneur/ dict || Bethune. herault darmes. ons ghenadichs heerẽ dẽ || Keysere Chaerles. || ¶ Gheprent Tantwerpẽ by mi Adriaen van || Bergen int gulden Missael. || ¶ Cum Priuilegio. In-4 goth. de 4 f. de 33 lignes à la page pleine, impr. en grosses lettres de forme, sign. A, mar. r. jans., tr. dor. (Trautz-Bauzonnet.)

Ladam (Nicaise). Epistel van de stadt van Rodes (1522)

¶ LE VOYAGE et || expedition de Charles le quint em- || pereur en Africque cõtre la || ville de Argiere. || ¶ La description de larmee & voyage de || Lempereur en Africque contre la || ville de Argiere / enuoyee a || mõsieur de Langest / tra- || duicte de latin en || françois. || ¶ Mil. D. xlii [1542] || ¶ On les vend a Paris en la rue sainct Ia- || ques a lenseigne des troys Brochetz / par Be- || noist de Gourmont. In-8 de 20 f. non chiffr. de 25 lignes à la page, sign. A-E par 4, mar. br., riches entrelacs et rinceaux en mosaïque de mar. vert, citron et rouge, doublé de mar. bleu, feuillages à petits fers, dos orné, gardes de moire bleue, tr. dor., dans un étui de mar. v. (Lortic.)

Charles Quint, roi d'Espagne et empereur d'Allemagne, d'abord archiduc d'Autriche. Le Voyage et Expedition de Charles le quint en Africque contre la ville de Argiere (1542)

VOLUMES RELIES du Cabinet des titres : recherches de noblesse, armoriaux, preuves, histoires généalogiques. « La dessente et filiation des seigneurs du Puy du Fou, au bas Poitou, prouvée par titres..., recueilli par les soins de Mre Gabriel, dernier marquis du nom, et des armes DU PUY DU FOU. » (1668).

A la suite : « Généalogie de l'ancienne et illustre maison de La Rochefoucaud,... par André DUCHESNE, géographe du Roy. »

VOLUMES RELIES du Cabinet des titres : recherches de noblesse, armoriaux, preuves, histoires généalogiques. Mélanges sur la noblesse de Normandie.

Contient : I ; « Les noms, et surnoms et demeure des nobles personnes du duché de Normandie, certifiés... par Remond de Montfault... » (1463) ; « Registre et estats des nouveaux anoblis en la province de Normandie, depuis les recherches qui furent faite par Rémont de Montfond... » (XVIe et XVIIe siècles) ; II « Généalogies des gentilshommes de l'élection de Bayeux, par eux produites, avec les titres justificatifs de leur noblesse, en l'an 1523 » ; III « Recherche des éleux de Lizieux par Nicolas Le Vallois, et François Le Roy et Jean Hédiart, escuyers, éleux de Lizieux... » (1540)

VOLUMES RELIES du Cabinet des titres : recherches de noblesse, armoriaux, preuves, histoires généalogiques. « Les Armes et blasons des chevaliers de l'Ordre du Sainct-Esprit, créez par Louis XIII,... par Jacques MORIN, escuier, sieur de La Masserie. — Paris, 1623, » in-4°.

Le faux-titre porte : « Chevaliers et commandeurs de l'Ordre du S. Esprit créez au chapitre tenu par le roy Louys XIII. en l'église des Augustins à Paris, le dernier jour de l'an 1619. » — Blasons gravés.

Fenofibrate: a new treatment for diabetic retinopathy. Molecular mechanisms and future perspectives.

Despite improving standards of care, people with diabetes remain at risk of development and progression of diabetic retinopathy (DR) and visual impairment. Identifying novel therapeutic approaches, preferably targeting more than one pathogenic pathway in DR, and at an earlier stage of disease, is attractive. There is now consistent evidence from two major trials, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study and the Action to Control Cardiovascular Risk in Diabetes Eye (ACCORD-Eye) study, totalling 11,388 people with type 2 diabetes (5,701 treated with fenofibrate) that fenofibrate reduces the risk of development and progression of DR. Therefore, fenofibrate may be considered a preventive strategy for patients without DR or early intervention strategy for those with mild DR. A number of putative therapeutic mechanisms for fenofibrate, both dependent and independent of lipids, have been proposed. A deeper understanding of the mode of action of fenofibrate will further help to define how best to use fenofibrate clinically as an adjunct to current management of DR.

Alu expression in human cell lines and their retrotranspositional potential.

BACKGROUND: The vast majority of the 1.1 million Alu elements are retrotranspositionally inactive, where only a few loci referred to as 'source elements' can generate new Alu insertions. The first step in identifying the active Alu sources is to determine the loci transcribed by RNA polymerase III (pol III). Previous genome-wide analyses from normal and transformed cell lines identified multiple Alu loci occupied by pol III factors, making them candidate source elements. FINDINGS: Analysis of the data from these genome-wide studies determined that the majority of pol III-bound Alus belonged to the older subfamilies Alu S and Alu J, which varied between cell lines from 62.5% to 98.7% of the identified loci. The pol III-bound Alus were further scored for estimated retrotransposition potential (ERP) based on the absence or presence of selected sequence features associated with Alu retrotransposition capability. Our analyses indicate that most of the pol III-bound Alu loci candidates identified lack the sequence characteristics important for retrotransposition. CONCLUSIONS: These data suggest that Alu expression likely varies by cell type, growth conditions and transformation state. This variation could extend to where the same cell lines in different laboratories present different Alu expression patterns. The vast majority of Alu loci potentially transcribed by RNA pol III lack important sequence features for retrotransposition and the majority of potentially active Alu loci in the genome (scored high ERP) belong to young Alu subfamilies. Our observations suggest that in an in vivo scenario, the contribution of Alu activity on somatic genetic damage may significantly vary between individuals and tissues.

Aromatherapy and nursing: historical and theoretical conception

Abstract Aromatherapy is a Practical or Complementary Health Therapy that uses volatile concentrates extracted from plants called essential oils, in order to improve physical, mental and emotional well-being. Aromatherapy has been practiced historically and worldwide by nurses and, as in Brazil is supported by the Federal Nursing Council, it is relevant to discuss this practice in the context of Nursing through Theories of Nursing. This study of theoretical reflection, exploratory and descriptive, aims to discuss the pharmacognosy of essential oils, the historical trajectory of Aromatherapy in Nursing and the conceptions to support Aromatherapy in light of eight Nursing Theorists (Florence Nightingale, Myra Levine, Hildegard Peplau, Martha Rogers, Callista Roy, Wanda Horta, Jean Watson and Katharine Kolcaba), contributing to its inclusion as a nursing care practice.