Inhibition of AP-1 binding and transcription by gold and selenium involving conserved cysteine residues in Jun and Fos.

Gold(I) salts and selenite, which have diverse therapeutic and biological effects, are noted for their reactivity with thiols. Since the binding of Jun-Jun and Jun-Fos dimers to the AP-1 DNA binding site is regulated in vitro by a redox process involving conserved cysteine residues, we hypothesized that some of the biological actions of gold and selenium are mediated via these residues. In electrophoretic mobility-shift analyses, AP-1 DNA binding was inhibited by gold(I) thiolates and selenite, with 50% inhibition occurring at approximately 5 microM and 1 microM, respectively. Thiomalic acid had no effect in the absence of gold(I), and other metal ions inhibited at higher concentrations, in a rank order correlating with their thiol binding affinities. Cysteine-to-serine mutants demonstrated that these effects of gold(I) and selenite require Cys272 and Cys154 in the DNA-binding domains of Jun and Fos, respectively. Gold(I) thiolates and selenite did not inhibit nonspecific protein binding to the AP-1 site and were at least an order of magnitude less potent as inhibitors of sequence-specific binding to the AP-2, TFIID, or NF1 sites compared with the AP-1 site. In addition, 10 microM gold(I) or 10 microM selenite inhibited expression of an AP-1-dependent reporter gene, but not an AP-2-dependent reporter gene. These data suggest a mechanism regulating transcription factor activity by inorganic ions which may contribute to the known antiarthritic action of gold and cancer chemoprevention by selenium.

A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase.

E6-AP is a 100-kDa cellular protein that interacts with the E6 protein of the cancer-associated human papillomavirus types 16 and 18. The E6/E6-AP complex binds to and targets the p53 tumor-suppressor protein for ubiquitin-mediated proteolysis. E6-AP is an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. The amino acid sequence of E6-AP shows similarity to a number of protein sequences over an approximately 350-aa region corresponding to the carboxyl termini of both E6-AP and the E6-AP-related proteins. Of particular note is a conserved cysteine residue within the last 32-34 aa, which in E6-AP is likely to be the site of ubiquitin thioester formation. Two of the E6-AP-related proteins, a rat 100-kDa protein and a yeast 95-kDa protein (RSP5), both of previously unknown function, are shown here to form thioesters with ubiquitin. Mutation of the conserved cysteine residue of these proteins destroys their ability to accept ubiquitin. These data strongly suggest that the rat 100-kDa protein and RSP5, as well as the other E6-AP-related proteins, belong to a class of functionally related E3 ubiquitin-protein ligases, defined by a domain homologous to the E6-AP carboxyl terminus (hect domain).

Letters from Thomas ap Catesby Jones to William Tudor,

Two letters in which Jones requests that Tudor relay his regrets to José de la Mar for missing the general’s installation as president of Peru, and mentions he is sending Tudor an ensign to be used "at the Palace."

Projeto de conceção do Plano de Contas das autarquias locais a partir da evolução do SNC

O trabalho realizado, teve como objetivo final, o desenvolvimento de um projeto, com vista à elaboração de um plano de contas para as Autarquias Locais, baseado no SNC (Sistema de Normalização Contabilística) que se encontra em vigor desde 2009, para as empresas privadas, de acordo com o estabelecido no Decreto - Lei 237/2009. O novo plano de contas, constante do projeto, virá a substituir o POCAL (Plano Oficial de Contas das Autarquias Locais), que se encontra implementado desde 1999, através do Decreto-Lei 54-A, de 22 de Fevereiro, com obrigatoriedade do seu seguimento a partir de Janeiro de 2002, dando lugar ao SNCAL. Tal como se verificou, relativamente ao POCAL, que foi criado no seguimento do POCP (Plano Oficial de Contas Público). Também para este projeto de elaboração de um plano de contas para as Autarquias Locais, foi tido como base o tronco de contas e subcontas que se prevê venha a ser implementado no Setor Público, com a designação de SNCP.

Regional vegetation changes in the tropical Andes expressed as arboreal pollen (AP%), standardised ordination scores (DCA z-scores), and aquatic vegetation ratios (D/SS); files used for plots

We compare eight pollen records reflecting climatic and environmental change from the tropical Andes. Our analysis focuses on the last 50 ka, with particular emphasis on the Pleistocene to Holocene transition. We explore ecological grouping and downcore ordination results as two approaches for extracting environmental variability from pollen records. We also use the records of aquatic and shoreline vegetation as markers for lake level fluctuations, and precipitation change. Our analysis focuses on the signature of millennial-scale variability in the tropical Andes, in particular, Heinrich stadials and Greenland interstadials. We identify rapid responses of the tropical vegetation to this climate variability, and relate differences between sites to moisture sources and site sensitivity.