Chemical Chaperones Improve Protein Secretion and Rescue Mutant Factor VIII in Mice with Hemophilia A.

nefficient intracellular protein trafficking is a critical issue in the pathogenesis of a variety of diseases and in recombinant protein production. Here we investigated the trafficking of factor VIII (FVIII), which is affected in the coagulation disorder hemophilia A. We hypothesized that chemical chaperones may be useful to enhance folding and processing of FVIII in recombinant protein production, and as a therapeutic approach in patients with impaired FVIII secretion. A tagged B-domain-deleted version of human FVIII was expressed in cultured Chinese Hamster Ovary cells to mimic the industrial production of this important protein. Of several chemical chaperones tested, the addition of betaine resulted in increased secretion of FVIII, by increasing solubility of intracellular FVIII aggregates and improving transport from endoplasmic reticulum to Golgi. Similar results were obtained in experiments monitoring recombinant full-length FVIII. Oral betaine administration also increased FVIII and factor IX (FIX) plasma levels in FVIII or FIX knockout mice following gene transfer. Moreover, in vitro and in vivo applications of betaine were also able to rescue a trafficking-defective FVIII mutant (FVIIIQ305P). We conclude that chemical chaperones such as betaine might represent a useful treatment concept for hemophilia and other diseases caused by deficient intracellular protein trafficking

Putative interaction of brush cells with bicarbonate secreting cells in the proximal corpus mucosa

The gastric epithelium is protected from the highly acidic luminal content by alkaline mucus which is secreted from specialized epithelial cells. In the stomach of mice strong secretion of alkaline fluid was observed at the "gastric groove," the border between corpus and fundus mucosa. Since this region is characterized by numerous brush cells it was proposed that these cells might secrete alkaline solution as suggested for brush cells in the bile duct. In fact, it was found that in this region multiple cells express elements which are relevant for the secretion of bicarbonate, including carbonic anhydrase (CAII), the cystic fibrosis transmembrane conductance regulator (CFTR) and the Na+/H+ exchanger (NHE1). However, this cell population was distinct from brush cells which express the TRP-channel TRPM5 and are considered as putative sensory cells. The location of both cell populations in close proximity implies the possibility for a paracnne interaction. This view was substantiated by the finding that brush cells express prostaglandin synthase-1 (COX-1) and the neighboring cells a specific receptor type for prostaglandins. The notion that brush cells may be able to sense a local acidification was supported by the observation that they express the channel PKD1L3 which contributes to the acid responsiveness of gustatory sensory cells. The results support the concept that brush cells may sense the luminal content and influence via prostaglandins the secretion of alkaline solution

Uso de fibras naturales de lechuguilla como refuerzo en concreto

Esta investigación pretende encontrar materiales de construcción que sean económicos y durables. Las fibras de acero, de vidrio o poliméricas, son alternativas viables pero costosas. Las fibras naturales pueden ser una posibilidad real para los países en desarrollo, ya que están disponibles en grandes cantidades y representan una fuente renovable continua. La fibra es afectada principalmente por la alcalinidad de la matriz de concreto. La durabilidad del compuesto dependerá entonces de la protección que tenga la fibra y de las características de impermeabilidad propias de la matriz

Hierarchical propagation of structural features in protein nanomaterials

Natural high-performance materials have inspired the exploration of novel materials from protein building blocks. The ability of proteins to self-organize into amyloid-like nanofibrils has opened an avenue to new materials by hierarchical assembly processes. As the mechanisms by which proteins form nanofibrils are becoming clear, the challenge now is to understand how the nanofibrils can be designed to form larger structures with defined order. We here report the spontaneous and reproducible formation of ordered microstructure in solution cast films from whey protein nanofibrils. The structural features are directly connected to the nanostructure of the protein fibrils, which is itself determined by the molecular structure of the building blocks. Hence, a hierarchical assembly process ranging over more than six orders of magnitude in size is described. The fibril length distribution is found to be the main determinant of the microstructure and the assembly process originates in restricted capillary flow induced by the solvent evaporation. We demonstrate that the structural features can be switched on and off by controlling the length distribution or the evaporation rate without losing the functional properties of the protein nanofibrils

Hierarchical propagation of structural features in protein nanomaterials

Natural high-performance materials have inspired the exploration of novel materials from protein building blocks. The ability of proteins to self-organize into amyloid-like nanofibrils has opened an avenue to new materials by hierarchical assembly processes. As the mechanisms by which proteins form nanofibrils are becoming clear, the challenge now is to understand how the nanofibrils can be designed to form larger structures with defined order. We here report the spontaneous and reproducible formation of ordered microstructure in solution cast films from whey protein nanofibrils. The structural features are directly connected to the nanostructure of the protein fibrils, which is itself determined by the molecular structure of the building blocks. Hence, a hierarchical assembly process ranging over more than six orders of magnitude in size is described. The fibril length distribution is found to be the main determinant of the microstructure and the assembly process originates in restricted capillary flow induced by the solvent evaporation. We demonstrate that the structural features can be switched on and off by controlling the length distribution or the evaporation rate without losing the functional properties of the protein nanofibrils

The O3N2 and N2 abundance indicators revisited: improved calibrations based on CALIFA and T e-based literature data

Astronomy and Astrophysics 559 (2013): A114 reproduced with permission from Astronomy and AstrophysicsThe use of integral field spectroscopy is since recently allowing to measure the emission line fluxes of an increasingly large number of star-forming galaxies, both locally and at high redshift. Many studies have used these fluxes to derive the gas-phase metallicity of the galaxies by applying the so-called strong-line methods. However, the metallicity indicators that these datasets use were empirically calibrated using few direct abundance data points (Te-based measurements). Furthermore, a precise determination of the prediction intervals of these indicators is commonly lacking in these calibrations. Such limitations might lead to systematic errors in determining the gas-phase metallicity, especially at high redshift, which might have a strong impact on our understanding of the chemical evolution of the Universe. The main goal of this study is to review the most widely used empirical oxygen calibrations, O3N2 and N2, by using newdirect abundance measurements. We pay special attention to (1) the expected uncertainty of these calibrations as a function of the index value or abundance derived and (2) the presence of possible systematic offsets. This is possible thanks to the analysis of the most ambitious compilation of Te-based H ii regions to date. This new dataset compiles the Te-based abundances of 603 H ii regions extracted from the literature but also includes new measurements from the CALIFA survey. Besides providing new and improved empirical calibrations for the gas abundance, we also present a comparison between our revisited calibrations with a total of 3423 additional CALIFA H ii complexes with abundances derived using the ONS calibration from the literature. The combined analysis of T e-based and ONS abundances allows us to derive their most accurate calibration to date for both the O3N2 and N2 single-ratio indicators, in terms of all statistical significance, quality, and coverage of the parameters space. In particular, we infer that these indicators show shallower abundance dependencies and statistically significant offsets compared to others'. The O3N2 and N2 indicators can be empirically applied to derive oxygen abundances calibrations from either direct abundance determinations with random errors of 0.18 and 0.16, respectively, or from indirect ones (but based on a large amount of data), reaching an average precision of 0.08 and 0.09 dex (random) and 0.02 and 0.08 dex (systematic; compared to the direct estimations), respectivelyR.A. Marino is funded by the Spanish program of International Campus of Excellence Moncloa (CEI). D. Mast thank the Plan Nacional de Investigación y Desarrollo funding programs, AYA2012-31935 of the Spanish Ministerio de Economía y Competitividad, for the support given to this project. S.F.S thanks the the Ramón y Cajal project RyC-2011-07590 of the spanish Ministerio de Economía y Competitividad, for the support giving to this project. F.F.R.O. acknowledges the Mexican National Council for Science and Technology (CONACYT) for financial support under the program Estancias Postdoctorales y Sabáticas al Extranjero para la Consolidación de Grupos de Investigación, 2010-2012. We acknowledge financial support for the ESTALLIDOS collaboration by the Spanish Ministerio de Ciencia e Innovación under grant AYA2010- 21887-C04-03. BG-L also acknowledges support from the Spanish Ministerio de Economía y Competitividad (MINECO) under grant AYA2012- 39408-C02-02. J.F.-B. acknowledges financial support from the Ramón y Cajal Program and grant AYA2010-21322-C03-02 from the Spanish Ministry of Economy and Competitiveness (MINECO), as well as to the DAGAL network from the People’s Program (Marie Curie Actions) of the European Union’s Seventh Framework Program FP7/2007-2013/ under REA grant agreement number PITN-GA-2011-289313. CK has been funded by project AYA2010-21887 from the Spanish PNAYA. P.P. acknowledges support by the Fundação para a Ciência e a Tecnologia (FCT) under project FCOMP-01-0124-FEDER-029170 (Reference FCT PTDC/FIS-AST/3214/2012), funded by FCT-MEC (PIDDAC) and FEDER (COMPETE). R.M.G.D. and R.G.B. also acknowledge support from the Spanish Ministerio de Economía y Competitividad (MINECO) under grant AyA2010-15081. V.S., L.G., and A.M.M. acknowledge financial support from the Fundação para a Ciência e a Tecnologia (FCT) under program Ciência 2008 and the research grant PTDC/CTE-AST/112582/200

ANÁLISE DA SATISFAÇÃO DOS AGRICULTORES INTEGRANTES DO PROGRAMA “PROTETOR DAS ÁGUAS” NO MUNICÍPIO DE VERA CRUZ/RS

Os processos contínuos de urbanização, assim como fragmentações do solo a partir de práticas agrícolas, são fatores que agravam a degradação dos ambientes naturais crescendo a necessidade de preservação e recuperação das nascentes de água. Neste sentido, é possível manter uma conduta ativa entre poder público e sociedade, através do Pagamento por Serviço Ambiental (PSA). Com o atual contexto inovador e desafiador, este trabalho objetivou realizar um levantamento e análise das características quanto a percepção dos agricultores participantes do “Programa Protetor das Águas” em Vera Cruz/RS. A metodologia teve uma abordagem quali-quantitativo através de questionários exploratórios de múltipla escolha. A partir da interpretação dos questionários, constatou-se que das 42 famílias entrevistadas, 76,2% fazem parte do Programa a mais de 6 anos (desde a implantação do Programa no município) e, 95,2% do total de entrevistados afirmam que o principal motivo para integrar o Programa é a preocupação com a qualidade da água. Porém, apesar de não ser uma vantagem aparente, constata-se que o retorno financeiro poderia interferir na decisão de permanência e execução das atividades do projeto. Quanto as expectativas para os próximos anos, 45,2% enfatizaram que mesmo sem apoio financeiro continuariam apoiando o projeto por considerarem importantes as ações realizadas em prol do meio ambiente, assim como para melhora da qualidade água. Conclui-se que os integrantes do Programa priorizam a qualidade da água como principal benefício de suas ações, e, apesar do incentivo financeiro recebido, o valor não é o principal fator que influencia a adesão

The Iowa Homemaker vol.21, no.8

We Want to Be Likeable, Mary Ellen Sullivan, page 2 Cotton hose Enlist Glamour, Elizabeth Ann Murfield, page 3 Memorial Union Plans Food for a Year, Pat Garberson, page 4 Government Drafts Textiles, Patricia Hayes, page 5 Gay Clothes Boost Sally’s Morale, Virginia Brainard, page 7 War Revamps Textile World, Betty Roth, page 8 Dehydrated Foods Gain New Victories, Janet Wilson, page 9 What’s New in Home Economics, Dorothy Olson, page 10 Departmental Highlights, Lila Williamson, page 12 War Rations British Homemaking, Marabeth Paddock, page 13 Across Alumnae Desks, Marjorie Thomas, page 14 Bookmarks, Julie Wendel, page 15 File That Information, Barbara Burbank, page 17 Alums in the News, Bette Simpson, page 18 For Victory, Margaret Ann Kirchner, page 20 Spindles, Trymby Calhoun, page 2