The alpha-galactosidase A p.Arg118Cys variant does not cause a Fabry disease phenotype: data from individual patients and family studies

Acessível em: www.ncbi.nlm.nih.gov/pmc/articles/PMC4423738/Lysosomal α-galactosidase A (α-Gal) is the enzyme deficient in Fabry disease (FD), an X-linked glycosphingolipidosis caused by pathogenic mutations affecting the GLA gene. The early-onset, multi-systemic FD classical phenotype is associated with absent or severe enzyme deficiency, as measured by in vitro assays, but patients with higher levels of residual α-Gal activity may have later-onset, more organ-restricted clinical presentations. A change in the codon 118 of the wild-type α-Gal sequence, replacing basic arginine by a potentially sulfhydryl-binding cysteine residue - GLA p.(Arg118Cys) -, has been recurrently described in large FD screening studies of high-risk patients. Although the Cys118 allele is associated with high residual α-Gal activity in vitro, it has been classified as a pathogenic mutation, mainly on the basis of theoretical arguments about the chemistry of the cysteine residue. However its pathogenicity has never been convincingly demonstrated by pathology criteria. We reviewed the clinical, biochemical and histopathology data obtained from 22 individuals of Portuguese and Spanish ancestry carrying the Cys118 allele, including 3 homozygous females. Cases were identified either on the differential diagnosis of possible FD manifestations and on case-finding studies (n=11; 4 males), or on unbiased cascade screening of probands' close relatives (n=11; 3 males). Overall, those data strongly suggest that the GLA p.(Arg118Cys) variant does not segregate with FD clinical phenotypes in a Mendelian fashion, but might be a modulator of the multifactorial risk of cerebrovascular disease. The Cys118 allelic frequency in healthy Portuguese adults (n=696) has been estimated as 0.001, therefore not qualifying for "rare" condition

Influence of calcium additiions on the compressive strength and microstructure of alkali-activated ceramic sanitaryware

This is the peer reviewed version of the following article: Reig, L., Soriano Martinez, Lourdes, Tashima, M.M., Borrachero Rosado, María Victoria, Monzó Balbuena, José Mª, Paya Bernabeu, Jorge Juan. (2018). Influence of calcium additiions on the compressive strength and microstructure of alkali-activated ceramic sanitaryware.Journal of the American Ceramic Society, 101, null, 3094-3104. DOI: 10.1111/jace.15436 , which has been published in final form at http://doi.org/10.1111/jace.15436. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] The ceramic sanitary-ware market generates large amounts of waste, both during the production process and due to construction and demolition practices. In this paper, the effect of different amounts and calcium sources (calcium hydroxide Ca(OH)2, calcium aluminate cement CAC, Portland cement PC) on the alkaline activation of ceramic sanitary-ware waste (CSW) was assessed. Blended samples were activated with NaOH and sodium silicate solutions and cured for 3 and 7 days at 65°C. The maximum amount of calcium source-type added to the system varied according to its influence on the compactability of the mortars.CSW was physico-chemically characterized and the compressive strength development of activated samples was assessed on the mortars. The nature of the reaction products was analyzed in pastes, by X-ray diffraction, thermogravimetric analysis, infrared spectroscopy and microscopic studies. The results show a great positive influence with the addition of moderate amounts of Ca(OH)2, PC and CAC on the mechanical properties. Among the typical hydrates usually observed in plain water-hydrated PC or CAC, only AH3 and a small amount of C3AH6 were identified in the alkali-activated CSW/CAC blended pastes, which indicates that Al and Ca from PC, CAC and Ca(OH)2 are taken up in the newly formed (N,C)-A-S-H or C-A-S-H gels.Spanish Ministry of Science and Innovation, Grant/Award Number: APLIGEO BIA2015-70107-R, GEOCEDEM BIA 2011-26947; Electron Microscopy Service of the Universitat Politecnica de Valencia; FEDERReig, L.; Soriano Martinez, L.; Tashima, M.; Borrachero Rosado, MV.; Monzó Balbuena, JM.; Paya Bernabeu, JJ. (2018). Influence of calcium additiions on the compressive strength and microstructure of alkali-activated ceramic sanitaryware. Journal of the American Ceramic Society. 101:3094-3104. https://doi.org/10.1111/jace.15436S30943104101Shi, C., Jiménez, A. F., & Palomo, A. (2011). New cements for the 21st century: The pursuit of an alternative to Portland cement. Cement and Concrete Research, 41(7), 750-763. doi:10.1016/j.cemconres.2011.03.016Halicka, A., Ogrodnik, P., & Zegardlo, B. (2013). Using ceramic sanitary ware waste as concrete aggregate. Construction and Building Materials, 48, 295-305. doi:10.1016/j.conbuildmat.2013.06.063Medina, C., Frías, M., & Sánchez de Rojas, M. I. (2012). Microstructure and properties of recycled concretes using ceramic sanitary ware industry waste as coarse aggregate. Construction and Building Materials, 31, 112-118. doi:10.1016/j.conbuildmat.2011.12.075Medina, C., Sánchez de Rojas, M. I., & Frías, M. (2012). Reuse of sanitary ceramic wastes as coarse aggregate in eco-efficient concretes. Cement and Concrete Composites, 34(1), 48-54. doi:10.1016/j.cemconcomp.2011.08.015Guerra, I., Vivar, I., Llamas, B., Juan, A., & Moran, J. (2009). Eco-efficient concretes: The effects of using recycled ceramic material from sanitary installations on the mechanical properties of concrete. Waste Management, 29(2), 643-646. doi:10.1016/j.wasman.2008.06.018Pacheco-Torgal, F., & Jalali, S. (2010). Reusing ceramic wastes in concrete. Construction and Building Materials, 24(5), 832-838. doi:10.1016/j.conbuildmat.2009.10.023Alves, A. V., Vieira, T. F., de Brito, J., & Correia, J. R. (2014). Mechanical properties of structural concrete with fine recycled ceramic aggregates. Construction and Building Materials, 64, 103-113. doi:10.1016/j.conbuildmat.2014.04.037Medina, C., Banfill, P. F. G., Sánchez de Rojas, M. I., & Frías, M. (2013). Rheological and calorimetric behaviour of cements blended with containing ceramic sanitary ware and construction/demolition waste. Construction and Building Materials, 40, 822-831. doi:10.1016/j.conbuildmat.2012.11.112Reig, L., Borrachero, M. V., Monzó, J. M., Savastano, H., Tashima, M. M., & Payá, J. (2015). Use of Ceramic Sanitaryware as an Alternative for the Development of New Sustainable Binders. Key Engineering Materials, 668, 172-180. doi:10.4028/www.scientific.net/kem.668.172Reig L Soriano L Borrachero MV Monzó J Payá J A new binder from the alkali activation of ceramic sanitary-ware waste Proceedings of the 34th Annual Cement and Concrete Science Conference, and Workshop on Waste Cementation, Sheffield, United Kingdom 2014 291 294Reig, L., Soriano, L., Borrachero, M. V., Monzó, J., & Payá, J. (2016). Influence of calcium aluminate cement (CAC) on alkaline activation of red clay brick waste (RCBW). Cement and Concrete Composites, 65, 177-185. doi:10.1016/j.cemconcomp.2015.10.021Arbi, K., Palomo, A., & Fernández-Jiménez, A. (2013). Alkali-activated blends of calcium aluminate cement and slag/diatomite. Ceramics International, 39(8), 9237-9245. doi:10.1016/j.ceramint.2013.05.031García-Lodeiro, I., Fernández-Jiménez, A., & Palomo, A. (2013). Variation in hybrid cements over time. Alkaline activation of fly ash–portland cement blends. Cement and Concrete Research, 52, 112-122. doi:10.1016/j.cemconres.2013.03.022Reig, L., Tashima, M. M., Soriano, L., Borrachero, M. V., Monzó, J., & Payá, J. (2013). Alkaline Activation of Ceramic Waste Materials. Waste and Biomass Valorization, 4(4), 729-736. doi:10.1007/s12649-013-9197-zReig, L., Soriano, L., Borrachero, M. V., Monzó, J., & Payá, J. (2014). Influence of the activator concentration and calcium hydroxide addition on the properties of alkali-activated porcelain stoneware. Construction and Building Materials, 63, 214-222. doi:10.1016/j.conbuildmat.2014.04.023Reig, L., Tashima, M. M., Borrachero, M. V., Monzó, J., Cheeseman, C. R., & Payá, J. (2013). Properties and microstructure of alkali-activated red clay brick waste. Construction and Building Materials, 43, 98-106. doi:10.1016/j.conbuildmat.2013.01.031Garcia-Lodeiro, I., Carcelen-Taboada, V., Fernández-Jiménez, A., & Palomo, A. (2016). Manufacture of hybrid cements with fly ash and bottom ash from a municipal solid waste incinerator. Construction and Building Materials, 105, 218-226. doi:10.1016/j.conbuildmat.2015.12.079Fernández-Jiménez, A., Palomo, Á., Vazquez, T., Vallepu, R., Terai, T., & Ikeda, K. (2008). Alkaline Activation of Blends of Metakaolin and Calcium Aluminate. Journal of the American Ceramic Society, 91(4), 1231-1236. doi:10.1111/j.1551-2916.2007.02002.xCriado, M., Fernández-Jiménez, A., & Palomo, A. (2007). Alkali activation of fly ash: Effect of the SiO2/Na2O ratio. Microporous and Mesoporous Materials, 106(1-3), 180-191. doi:10.1016/j.micromeso.2007.02.055Fernández-Jiménez, A., Vázquez, T., & Palomo, A. (2011). Effect of Sodium Silicate on Calcium Aluminate Cement Hydration in Highly Alkaline Media: A Microstructural Characterization. Journal of the American Ceramic Society, 94(4), 1297-1303. doi:10.1111/j.1551-2916.2010.04242.xBernal, S. A., de Gutierrez, R. M., Provis, J. L., & Rose, V. (2010). Effect of silicate modulus and metakaolin incorporation on the carbonation of alkali silicate-activated slags. Cement and Concrete Research, 40(6), 898-907. doi:10.1016/j.cemconres.2010.02.003Pacewska, B., Nowacka, M., Antonovič, V., & Aleknevičius, M. (2012). Investigation of early hydration of high aluminate cement-based binder at different ambient temperatures. Journal of Thermal Analysis and Calorimetry, 109(2), 717-726. doi:10.1007/s10973-012-2233-6Mas, M. A., Monzó, J., Payá, J., Reig, L., & Borrachero, M. V. (2016). Ceramic tiles waste as replacement material in Portland cement. Advances in Cement Research, 28(4), 221-232. doi:10.1680/jadcr.15.00021Hidalgo, A., García, J. L., Alonso, M. C., Fernández, L., & Andrade, C. (2009). Microstructure development in mixes of calcium aluminate cement with silica fume or fly ash. Journal of Thermal Analysis and Calorimetry, 96(2), 335-345. doi:10.1007/s10973-007-8439-3Pacewska, B., Wilińska, I., & Nowacka, M. (2011). Studies on the influence of different fly ashes and Portland cement on early hydration of calcium aluminate cement. Journal of Thermal Analysis and Calorimetry, 106(3), 859-868. doi:10.1007/s10973-011-1570-1Fernández-Carrasco, L., & Vázquez, E. (2009). Reactions of fly ash with calcium aluminate cement and calcium sulphate. Fuel, 88(9), 1533-1538. doi:10.1016/j.fuel.2009.02.018Fernández-Carrasco, L., Torréns-Martín, D., & Martínez-Ramírez, S. (2012). Carbonation of ternary building cementing materials. Cement and Concrete Composites, 34(10), 1180-1186. doi:10.1016/j.cemconcomp.2012.06.016García Lodeiro, I., Macphee, D. E., Palomo, A., & Fernández-Jiménez, A. (2009). Effect of alkalis on fresh C–S–H gels. FTIR analysis. Cement and Concrete Research, 39(3), 147-153. doi:10.1016/j.cemconres.2009.01.003Lavat, A. E., Trezza, M. A., & Poggi, M. (2009). Characterization of ceramic roof tile wastes as pozzolanic admixture. Waste Management, 29(5), 1666-1674. doi:10.1016/j.wasman.2008.10.019Garcia-Lodeiro, I., Palomo, A., Fernández-Jiménez, A., & Macphee, D. E. (2011). Compatibility studies between N-A-S-H and C-A-S-H gels. Study in the ternary diagram Na2O–CaO–Al2O3–SiO2–H2O. Cement and Concrete Research, 41(9), 923-931. doi:10.1016/j.cemconres.2011.05.006Fernández-Carrasco, L., & Vázquez, T. (1996). Aplicación de la espectroscopia infrarroja al estudio de cemento aluminoso. Materiales de Construcción, 46(241), 39-51. doi:10.3989/mc.1996.v46.i241.540Rees, C. A., Provis, J. L., Lukey, G. C., & van Deventer, J. S. J. (2007). Attenuated Total Reflectance Fourier Transform Infrared Analysis of Fly Ash Geopolymer Gel Aging. Langmuir, 23(15), 8170-8179. doi:10.1021/la700713gGranizo, M. L., Alonso, S., Blanco-Varela, M. T., & Palomo, A. (2004). Alkaline Activation of Metakaolin: Effect of Calcium Hydroxide in the Products of Reaction. Journal of the American Ceramic Society, 85(1), 225-231. doi:10.1111/j.1151-2916.2002.tb00070.xLiu, Y., Yan, C., Qiu, X., Li, D., Wang, H., & Alshameri, A. (2016). Preparation of faujasite block from fly ash-based geopolymer via in-situ hydrothermal method. Journal of the Taiwan Institute of Chemical Engineers, 59, 433-439. doi:10.1016/j.jtice.2015.07.01

Genetic and phenotypic variation of the malaria vector Anopheles atroparvus in southern Europe

<p>Abstract</p> <p>Background</p> <p>There is a growing concern that global climate change will affect the potential for pathogen transmission by insect species that are vectors of human diseases. One of these species is the former European malaria vector, <it>Anopheles atroparvus</it>. Levels of population differentiation of <it>An. atroparvus </it>from southern Europe were characterized as a first attempt to elucidate patterns of population structure of this former malaria vector. Results are discussed in light of a hypothetical situation of re-establishment of malaria transmission.</p> <p>Methods</p> <p>Genetic and phenotypic variation was analysed in nine mosquito samples collected from five European countries, using eight microsatellite loci and geometric morphometrics on 21 wing landmarks.</p> <p>Results</p> <p>Levels of genetic diversity were comparable to those reported for tropical malaria vectors. Low levels of genetic (0.004 <<it>F</it>_{<it>ST </it>}<0.086) and phenotypic differentiation were detected among <it>An. atroparvus </it>populations spanning over 3,000 km distance. Genetic differentiation (0.202 <<it>F</it>_{<it>ST </it>}<0.299) was higher between the sibling species <it>An. atroparvus </it>and <it>Anopheles maculipennis </it>s.s. Differentiation between sibling species was not so evident at the phenotype level.</p> <p>Conclusions</p> <p>Levels of population differentiation within <it>An. atroparvus </it>were low and not correlated with geographic distance or with putative physical barriers to gene flow (Alps and Pyrenées). While these results may suggest considerable levels of gene flow, other explanations such as the effect of historical population perturbations can also be hypothesized.</p