Zalpha-domains: At the intersection between RNA editing and innate immunity

The involvement of A to I RNA editing in antiviral responses was first indicated by the observation of genomic hyper-mutation for several RNA viruses in the course of persistent infections. However, in only a few cases an antiviral role was ever demonstrated and surprisingly, it turns out that ADARs - the RNA editing enzymes - may have a prominent pro-viral role through the modulation/down-regulation of the interferon response. A key role in this regulatory function of RNA editing is played by ADAR1, an interferon inducible RNA editing enzyme. A distinguishing feature of ADAR1, when compared with other ADARs, is the presence of a Z-DNA binding domain, Zalpha. Since the initial discovery of the specific and high affinity binding of Zalpha to CpG repeats in a left-handed helical conformation, other proteins, all related to the interferon response pathway, were shown to have similar domains throughout the vertebrate lineage. What is the biological function of this domain family remains unclear but a significant body of work provides pieces of a puzzle that points to an important role of Zalpha domains in the recognition of foreign nucleic acids in the cytoplasm by the innate immune system. Here we will provide an overview of our knowledge on ADAR1 function in interferon response with emphasis on Zalpha domains.

Evidence for a Myotomal Hox/Myf Cascade Governing Nonautonomous Control of Rib Specification within Global Vertebral Domains

Hox genes are essential for the patterning of the axial skeleton. Hox group 10 has been shown to specify the lumbar domain by setting a rib-inhibiting program in the presomitic mesoderm (PSM). We have now produced mice with ribs in every vertebra by ectopically expressing Hox group 6 in the PSM, indicating that Hox genes are also able to specify the thoracic domain. We show that the information provided by Hox genes to specify rib-containing and rib-less areas is first interpreted in the myotome through the regional-specific control of Myf5 and Myf6 expression. This information is then transmitted to the sclerotome by a system that includes FGF and PDGF signaling to produce vertebrae with or without ribs at different axial levels. Our findings offer a new perspective of how Hox genes produce global patterns in the axial skeleton and support a redundant nonmyogenic role of Myf5 and Myf6 in rib formation.

Palavras que nos embalam: a escrita criativa no 1º ciclo do ensino básico

A leitura e a escrita mantêm entre si relações de grande proximidade sendo praticamente indissociáveis. Na verdade, nas últimas décadas, a investigação tem vindo a demonstrar que a aprendizagem da leitura e da escrita se processa praticamente em simultâneo e que, ao longo do processo de ensino-aprendizagem, essa relação entre os dois domínios se vai intensificando. Assim, sabemos hoje, que quanto mais se lê melhor se escreve, da mesma forma que quanto mais se escreve maior é a capacidade de compreender os textos lidos. Ao professor de Português compete a tarefa de desenvolver nos seus alunos, em qualquer nível de ensino, competências várias em todos os domínios contemplados nos documentos legais e programáticos em vigor. No entanto, e dada a natureza deste Relatório Final de Prática de Ensino Supervisionada, não podemos deixar de frisar que, relativamente aos domínios da leitura e da escrita, o professor de língua materna deve promover e estimular nos seus alunos o desenvolvimento gradual e articulado de competências relacionadas com a compreensão leitora e a expressão escrita, nas suas várias dimensões – ortográfica, textual e criativa. Encarando a escrita criativa como uma modalidade fundamental para a criança, não só por alargar a sua capacidade imaginativa, mas também por permitir adquirir, consolidar e utilizar com progressiva autonomia e criatividade todos os aspetos relacionados com a estrutura da língua, perspetivamo-la como fundamental nas aulas de Português, pelas potencialidades de que a mesma se reveste e não apenas como ferramenta utilizada para desbloquear nos alunos o receio da página em branco. Daí que tenhamos concebido e implementado, numa sala de 3º ano de escolaridade, num dos agrupamentos de escolas de Portalegre, um projeto de investigação-ação centrado no domínio da escrita criativa, mas alicerçado em práticas de leitura compreensiva de textos literários, práticas essas que antecederam os momentos de escrita. Desse projeto em particular, e das atividades implementadas ao longo da Prática de Ensino Supervisionada nas diversas disciplinas em geral, no 1º e no 2º CEB, dar-se-á conta, de forma reflexiva, neste Relatório Final.

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

The Charles Butler collections : Catalogue of the collection of coins and medals formed by the late Charles Butler, esq., comprising ancient Greek coins in gold and silver...Roman Republican and Imperial coins...English coins in gold, silver and bronze, foreign coins, etc., which will be sold by auction by messrs. Sotheby, Wilkinson & Hodge at their house...Monday 3rd July, 1911.

Mode of access: Internet.

XVII and XVIII century American furniture and contemporary decorations, comprising the collection exhibited, during the summer at King Hooper mansion, Marblehead., Mass., owned and operated by King Hooper, Inc. Also choicest specimens from the collection of Hyman Kaufman, Boston, and the collection of silver of Herbert Lawton, Boston, sold by their order; unrestricted public auction sale, Thursday, Friday and Saturday, December 3rd, 4th and 5th, 1931 ...

"Sale number twenty-two."

2nd, 3rd, 4th and 5th interim reports ...

Mode of access: Internet.

Rhinebeck birds and seasons : articles published in the Rhinebeck gazette October 3rd, 1914 to September 25, 1915 /

"To which is added The second annual report of the Rhinebeck Bird Club."

8 pianoforte studies for the development of the 3rd, 4th, & 5th fingers : op. 21.

Mode of access: Internet.

Mines (eight hours) bill, 1893. (Appointed for 2nd reading 3rd May, 1893.) Summary: digest of evidence given before group "A" committee of the Royal Commission on Labour in reference to the above, and print of the bill.

Mode of access: Internet.

Manual of the international list of causes of death : based on the 3rd decennial revision of the International Commission, Paris, Octobe 11 to 15, 1920.

At head of title: Department of Commerce and Labor. Bureau of the Census. W.M. Steuart, director.

Proceedings of the Nicaragua Canal Convention held at St. Louis, Mo. : in the Exposition Music Hall on the 2nd and 3rd days of June, 1892.

Includes addresses by M. M. Estee, W. Miller, and D. R. Francis.