Percorrer por autor "Sousa, I."
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- Anti-corrosion and cytotoxicity properties of inorganic surface treatments on Mg1Ca biodegradable alloyPublication . Neves, C.S.; Sousa, I.; Freitas, M.A.; Moreira, L.; Costa, C.; Teixeira, J.P.; Fraga, S.; Silva, R.M.; Silva, R.F.; Starykevich, M.; Scharnagl, N.; Zheludkevich, M.L.; Ferreira, M.G.S.; Tedim, J.In this work biodegradable Mg1Ca alloy underwent surface modification using hydroxyapatite (HAp), aluminium oxide (Al2O3), and treatments with phosphoric (H3PO4), hydrofluoric (HF), and acetic (CH3COOH) acids. The resulting surface-treated Mg substrates were assessed in terms of phase content and chemical composition through X-ray diffraction (XRD) and glow discharge optical emission spectrometry (GDOES). Additionally, atomic force microscopy (AFM) and scanning electron microscopy (SEM) were employed to examine the surface's topography and structure, while the corrosion behavior and cytotoxicity were surveyed using electrochemical impedance spectroscopy (EIS), alongside WST-1 reduction and lactate dehydrogenase (LDH) release assays on L929 mouse fibroblasts. The findings indicated that the surfaces of all samples were uniformly structured, while chemical analysis of the treated surfaces suggested the presence of mostly thin films. Furthermore, EIS results highlighted that the HAp-treated Mg1Ca alloy exhibited superior corrosion resistance, and the cytotoxicity assessment of Mg1Ca-HAp and Mg1Ca-H3PO4 alloys showed minimal cytotoxic effects on mouse fibroblasts, compared to other treated surfaces, suggesting enhanced biocompatibility of those two surface treatments. Overall, this constitutes the first comparative study of different surface treatments developed on biodegradable Mg1Ca alloy, aiming to identify optimal modification strategies for biomedical applications.
- Evidence for epistasis between SLC6A4 and ITGB3 in autism etiology and in the determination of platelet serotonin levelsPublication . Coutinho, A.M.; Sousa, I.; Martins, M.; Correia, C.; Morgadinho, T.; Bento, C.; Marques, C.; Ataíde, A.; Miguel, T.S.; Moore, J.H.; Oliveira, G.; Vicente, A.M.Autism is a neurodevelopmental disorder of unclear etiology. The consistent finding of platelet hyperserotonemia in a proportion of patients and its heritability within affected families suggest that genes involved in the serotonin system play a role in this disorder. The role in autism etiology of seven candidate genes in the serotonin metabolic and neurotransmission pathways and mapping to autism linkage regions (SLC6A4, HTR1A, HTR1D, HTR2A, HTR5A, TPH1 and ITGB3) was analyzed in a sample of 186 nuclear families. The impact of interactions among these genes in autism was assessed using the multifactor-dimensionality reduction (MDR) method in 186 patients and 181 controls. We further evaluated whether the effect of specific gene variants or gene interactions associated with autism etiology might be mediated by their influence on serotonin levels, using the quantitative transmission disequilibrium test (QTDT) and the restricted partition method (RPM), in a sample of 109 autistic children. We report a significant main effect of the HTR5A gene in autism (P = 0.0088), and a significant three-locus model comprising a synergistic interaction between the ITGB3 and SLC6A4 genes with an additive effect of HTR5A (P < 0.0010). In addition to the previously reported contribution of SLC6A4, we found significant associations of ITGB3 haplotypes with serotonin level distribution (P = 0.0163). The most significant models contributing to serotonin distribution were found for interactions between TPH1 rs4537731 and SLC6A4 haplotypes (P = 0.002) and between HTR1D rs6300 and SLC6A4 haplotypes (P = 0.013). In addition to the significant independent effects, evidence for interaction between SLC6A4 and ITGB3 markers was also found. The overall results implicate SLC6A4 and ITGB3 gene interactions in autism etiology and in serotonin level determination, providing evidence for a common underlying genetic mechanism and a molecular explanation for the association of platelet hyperserotonemia with autism.
- Functional impact of global rare copy number variation in autism spectrum disordersPublication . Pinto, D.; Pagnamenta, A.T.; Klei, L.; Anney, R.; Merico, D.; Regan, R.; Conroy, J.; Magalhaes, T.R.; Correia, C.; Abrahams, B.S.; Almeida, J.; Bacchelli, E.; Bader, G.D.; Bailey, A.J.; Baird, G.; Battaglia, A.; Berney, T.; Bolshakova, N.; Bölte, S.; Bolton, P.F.; Bourgeron, T.; Brennan, S.; Brian, J.; Bryson, S.E.; Carson, A.R.; Casallo, G.; Casey, J.; Chung, B.H.; Cochrane, L.; Corsello, C.; Crawford, E.L.; Crossett, A.; Cytrynbaum, C.; Dawson, G.; de Jonge, M.; Delorme, R.; Drmic, I.; Duketis, E.; Duque, F.; Estes, A.; Farrar, P.; Fernandez, B.A.; Folstein, S.E.; Fombonne, E.; Freitag, C.M.; Gilbert, J.; Gillberg, C.; Glessner, J.T.; Goldberg, J.; Green, A.; Green, J.; Guter, S.J.; Hakonarson, H.; Heron, E.A.; Hill, M.; Holt, R.; Howe, J.L.; Hughes, G.; Hus, V.; Igliozzi, R.; Kim, C.; Klauck, S.M.; Kolevzon, A.; Korvatska, O.; Kustanovich, V.; Lajonchere, C.M.; Lamb, J.A.; Laskawiec, M.; Leboyer, M.; Le Couteur, A.; Leventhal, B.L.; Lionel, A.C.; Liu, X.Q.; Lord, C.; Lotspeich, L.; Lund, S.C.; Maestrini, E.; Mahoney, W.; Mantoulan, C.; Marshall, C.R.; McConachie, H.; McDougle, C.J.; McGrath, J.; McMahon, W.M.; Merikangas, A.; Migita, O.; Minshew, N.J.; Mirza, G.K.; Munson, J.; Nelson, S.F.; Noakes, C.; Noor, A.; Nygren, G.; Oliveira, G.; Papanikolaou, K.; Parr, J.R.; Parrini, B.; Paton, T.; Pickles, A.; Pilorge, M.; Piven, J.; Ponting, C.P.; Posey, D.J.; Poustka, A.; Poustka, F.; Prasad, A.; Ragoussis, J.; Renshaw, K.; Rickaby, J.; Roberts, W.; Roeder, K.; Roge, B.; Rutter, M.L.; Bierut, L.J.; Rice, J.P.; Salt, J.; Sansom, K.; Sato, D.; Segurado, R.; Sequeira, A.F.; Senman, L.; Shah, N.; Sheffield, V.C.; Soorya, L.; Sousa, I.; Stein, O.; Sykes, N.; Stoppioni, V.; Strawbridge, C.; Tancredi, R.; Tansey, K.; Thiruvahindrapduram, B.; Thompson, A.P.; Thomson, S.; Tryfon, A.; Tsiantis, J.; Van Engeland, H.; Vincent, J.B.; Volkmar, F.; Wallace, S.; Wang, K.; Wang, Z.; Wassink, T.H.; Webber, C.; Weksberg, R.; Wing, K.; Wittemeyer, K.; Wood, S.; Wu, J.; Yaspan, B.L.; Zurawiecki, D.; Zwaigenbaum, L.; Buxbaum, J.D.; Cantor, R.M.; Cook, E.H.; Coon, H.; Cuccaro, M.L.; Devlin, B.; Ennis, S.; Gallagher, L.; Geschwind, D.H.; Gill, M.; Haines, J.L.; Hallmayer, J.; Miller, J.; Monaco, A.P.; Nurnberger Jr, J.I.; Paterson, A.D.; Pericak-Vance, M.A.; Schellenberg, G.D.; Szatmari, P.; Vicente, A.M.; Vieland, V.J.; Wijsman, E.M.; Scherer, S.W.; Sutcliffe, J.S.; Betancur, C.The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
- Gene-ontology enrichment analysis in two independent family-based samples highlights biologically plausible processes for autism spectrum disordersPublication . Anney, R.J.; Kenny, E.M.; O'Dushlaine, C.; Parkhomenka, E.; Buxbaum, J.D.; Sutcliffe, J.; Gill, M.; Gallagher, L.; Bailey, A.J.; Fernandez, B.A.; Szatmari, P.; Nurnberger Jr, J.I.; McDougle, C.J.; Posey, D.J.; Lord, C.; Corsello, C.; Hus, V.; Buxbaum, J.D.; Kolevzon, A.; Soorya, L.; Parkhomenko, E.; Scherer, S.W.; Leventhal, B.L.; Dawson, G.; Vieland, V.J.; Hakonarson, H.; Glessner, J.T.; Kim, C.; Wang, K.; Schellenberg, G.D.; Devlin, B.; Klei, L.; Patterson, A.; Minshew, N.; Sutcliffe, J.S.; Haines, J.L.; Lund, S.C.; Thomson, S.; Yaspan, B.L.; Coon, H.; Miller, J.; McMahon, W.M.; Munson, J.; Marshall, C.R.; Estes, A.; Wijsman, EM.; The Autism Genome Project; Pinto, D.; Vincent, J.B.; Fombonne, E.; Betancur, C.; Delorme, R.; Leboyer, M.; Bourgeron, T.; Mantoulan, C.; Roge, B.; Tauber, M.; Freitag, C.M.; Poustka, F.; Duketis, E.; Klauck, S.M.; Poustka, A.; Papanikolaou, K.; Tsiantis, J.; Gallagher, L.; Gill, M.; Anney, R.; Bolshakova, N.; Brennan, S.; Hughes, G.; McGrath, J.; Merikangas, A.; Ennis, S.; Green, A.; Casey, J.P.; Conroy, J.M.; Regan, R.; Shah, N.; Maestrini, E.; Bacchelli, E.; Minopoli, F.; Stoppioni, V.; Battaglia, A.; Igliozzi, R.; Parrini, B.; Tancredi, R.; Oliveira, G.; Almeida, J.; Duque, F.; Vicente, A.M.; Correia, C.; Magalhaes, T.R.; Gillberg, C.; Nygren, G.; Jonge, M.D.; Van Engeland, H.; Vorstman, J.A.; Wittemeyer, K.; Baird, G.; Bolton, P.F; Rutter, M.L.; Green, J.; Lamb, J.A.; Pickles, A.; Parr, J.R.; Couteur, A.L.; Berney, T.; McConachie, H.; Wallace, S.; Coutanche, M.; Foley, S.; White, K.; Monaco, A.P.; Holt, R.; Farrar, P.; Pagnamenta, A.T.; Mirza, G.K.; Ragoussis, J.; Sousa, I.; Sykes, N.; Wing, K.; Hallmayer, J.; Cantor, R.M.; Nelson, S.F.; Geschwind, D.H.; Abrahams, B.S.; Volkmar, F.; Pericak-Vance, M.A.; Cuccaro, M.L.; Gilbert, J.; Cook, E.H.; Guter, S.J.; Jacob, S.Recent genome-wide association studies (GWAS) have implicated a range of genes from discrete biological pathways in the aetiology of autism. However, despite the strong influence of genetic factors, association studies have yet to identify statistically robust, replicated major effect genes or SNPs. We apply the principle of the SNP ratio test methodology described by O'Dushlaine et al to over 2100 families from the Autism Genome Project (AGP). Using a two-stage design we examine association enrichment in 5955 unique gene-ontology classifications across four groupings based on two phenotypic and two ancestral classifications. Based on estimates from simulation we identify excess of association enrichment across all analyses. We observe enrichment in association for sets of genes involved in diverse biological processes, including pyruvate metabolism, transcription factor activation, cell-signalling and cell-cycle regulation. Both genes and processes that show enrichment have previously been examined in autistic disorders and offer biologically plausibility to these findings.
- A genome-wide scan for common alleles affecting risk for autismPublication . Anney, R.; Klei, L.; Pinto, D.; Regan, R.; Conroy, J.; Magalhaes, T.R.; Correia, C.; Abrahams, B.S.; Sykes, N.; Pagnamenta, A.T.; Almeida, J.; Bacchelli, E.; Bailey, A.J.; Baird, G.; Battaglia, A.; Berney, T.; Bolshakova, N.; Bölte, S.; Bolton, P.F.; Bourgeron, T.; Brennan, S.; Brian, J.; Carson, A.R.; Casallo, G.; Casey, J.; Chu, S.H.; Cochrane, L.; Corsello, C.; Crawford, E.L.; Crossett, A.; Dawson, G.; de Jonge, M.; Delorme, R.; Drmic, I.; Duketis, E.; Duque, F.; Estes, A.; Farrar, P.; Fernandez, B.A.; Folstein, S.E.; Fombonne, E.; Freitag, C.M.; Gilbert, J.; Gillberg, C.; Glessner, J.T.; Goldberg, J.; Green, J.; Guter, S.J.; Hakonarson, H.; Heron, E.A.; Hill, M.; Holt, R.; Howe, J.L.; Hughes, G.; Hus, V.; Igliozzi, R.; Kim, C.; Klauck, S.M.; Kolevzon, A.; Korvatska, O.; Kustanovich, V.; Lajonchere, C.M.; Lamb, J.A.; Laskawiec, M.; Leboyer, M.; Le Couteur, A.; Leventhal, B.L.; Lionel, A.C.; Liu, X.Q.; Lord, C.; Lotspeich, L.; Lund, S.C.; Maestrini, E.; Mahoney, W.; Mantoulan, C.; Marshall, C.R.; McConachie, H.; McDougle, C.J.; McGrath, J.; McMahon, W.M.; Melhem, N.M.; Merikangas, A.; Migita, O.; Minshew, N.J.; Mirza, G.K.; Munson, J.; Nelson, S.F.; Noakes, C.; Noor, A.; Nygren, G.; Oliveira, G.; Papanikolaou, K.; Parr, J.R.; Parrini, B.; Paton, T.; Pickles, A.; Piven, J.; Posey, D.J.; Poustka, A.; Poustka, F.; Prasad, A.; Ragoussis, J.; Renshaw, K.; Rickaby, J.; Roberts, W.; Roeder, K.; Roge, B.; Rutter, M.L.; Bierut, L.J.; Rice, J.P.; Salt, J.; Sansom, K.; Sato, D.; Segurado, R.; Senman, L.; Shah, N.; Sheffield, V.C.; Soorya, L.; Sousa, I.; Stoppioni, V.; Strawbridge, C.; Tancredi, R.; Tansey, K.; Thiruvahindrapduram, B.; Thompson, A.P.; Thomson, S.; Tryfon, A.; Tsiantis, J.; Van Engeland, H.; Vincent, J.B.; Volkmar, F.; Wallace, S.; Wang, K.; Wang, Z.; Wassink, T.H.; Wing, K.; Wittemeyer, K.; Wood, S.; Yaspan, B.L.; Zurawiecki, D.; Zwaigenbaum, L.; Betancur, C.; Buxbaum, J.D.; Cantor, R.M.; Cook, E.H.; Coon, H.; Cuccaro, M.L.; Gallagher, L.; Geschwind, D.H.; Gill, M.; Haines, J.L.; Miller, J.; Monaco, A.P.; Nurnberger Jr, J.I.; Paterson, A.D.; Pericak-Vance, M.A.; Schellenberg, G.D.; Scherer, S.W.; Sutcliffe, J.S.; Szatmari, P.; Vicente, A.M.; Vieland, V.J.; Wijsman, E.M.; Devlin, B.; Ennis, S.; Hallmayer, J.Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
- Glycosyl flavonoids from Salvia sclareoides: contribution to the development of a new functional foodPublication . Abraços, L.; Martins, A.; Neng, N.; Nogueira, J.M.F.; Serralheiro, M.L.; Batista, A.P.; Raymundo, A.; Sousa, I.; Albuquerque, T.G.; Costa, H.S.; Rauter, A.P.Salvia sclareoides is a plant of spontaneous Portuguese vegetation that has relevant properties, as part of its cholinergic action and in the prevention of the formation of amyloid plaques. Previous studies suggested [1,2] that this species of Salvia can be used as a functional food and also in the development of a food supplement in the context of the prevention and treatment of Alzheimer's disease. Sweet cookies were developed with different concentrations (2 % and 5 %) of S. sclareoides, previously ground for particle size reduction (2.00 mm). The nutritional composition was determined, namely: moisture content, ash, total protein, total fat, dietary fibre and salt [3]. The available carbohydrates and the energy value were obtained by calculation. Extracts were prepared from the dried aerial parts of the plant. Different extraction methodologies were used and the phenolic profile of each extract was determined by high performance liquid chromatography with diode array detection. The antioxidant and anticholinesterase activities of these extracts were also evaluated. The ethanol extract of S. sclareoides, with 2.00 mm grain size, presented the highest concentration of phenolic compounds (143.74 mg GAE/g dry extract) and antioxidant activity (68.45 %), while the aqueous extract showed the best anticholinesterase activity (30.86 %). The glycosylated flavonoids rutin and (7-O-glucosyl)luteolin are clearly the major constituents present in all extracts, along with epicatechin, ellagic acid and (7-O-glucosyl)naringenin.
- Individual common variants exert weak effects on the risk for autism spectrum disorderspiPublication . Anney, R.; Klei, L.; Pinto, D.; Almeida, J.; Bacchelli, E.; Baird, G.; Bolshakova, N.; Bölte, S.; Bolton, P.F.; Bourgeron, T.; Brennan, S.; Brian, J.; Casey, J.; Conroy, J.; Correia, C.; Corsello, C.; Crawford, E.L.; de Jonge, M.; Delorme, R.; Duketis, E.; Duque, F.; Estes, A.; Farrar, P.; Fernandez, B.A.; Folstein, S.E.; Fombonne, E.; Gilbert, J.; Gillberg, C.; Glessner, J.T.; Green, A.; Green, J.; Guter, S.J.; Heron, E.A.; Holt, R.; Howe, J.L.; Hughes, G.; Hus, V.; Igliozzi, R.; Jacob, S.; Kenny, G.P.; Kim, C.; Kolevzon, A.; Kustanovich, V.; Lajonchere, C.M.; Lamb, J.A.; Law-Smith, M.; Leboyer, M.; Le Couteur, A.; Leventhal, B.L.; Liu, X.Q.; Lombard, F.; Lord, C.; Lotspeich, L.; Lund, S.C.; Magalhaes, T.R.; Mantoulan, C.; McDougle, C.J.; Melhem, N.M.; Merikangas, A.; Minshew, N.J.; Mirza, G.K.; Munson, J.; Noakes, C.; Nygren, G.; Papanikolaou, K.; Pagnamenta, A.T.; Parrini, B.; Paton, T.; Pickles, A.; Posey, D.J.; Poustka, F.; Ragoussis, J.; Regan, R.; Roberts, W.; Roeder, K.; Roge, B.; Rutter, M.L.; Schlitt, S.; Shah, N.; Sheffield, V.C.; Soorya, L.; Sousa, I.; Stoppioni, V.; Sykes, N.; Tancredi, R.; Thompson, A.P.; Thomson, S.; Tryfon, A.; Tsiantis, J.; Van Engeland, H.; Vincent, J.B.; Volkmar, F.; Vorstman, J.; Wallace, S.; Wing, K.; Wittemeyer, K.; Wood, S.; Zurawiecki, D.; Zwaigenbaum, L.; Bailey, AJ; Battaglia, A.; Cantor, R.M.; Coon, H.; Cuccaro, M.L.; Dawson, G.; Ennis, S.; Freitag, C.M.; Geschwind, D.H.; Haines, J.L.; Klauck, S.M.; McMahon, W.M.; Maestrini, E.; Miller, J.; Monaco, A.P.; Nelson, S.F.; Nurnberger Jr, J.I.; Oliveira, G.; Parr, J.R.; Pericak-Vance, M.A.; Piven, J.; Schellenberg, G.D.; Scherer, S.W.; Vicente, A.M.; Wassink, T.H.; Wijsman, E.M.; Betancur, C.; Buxbaum, J.D.; Cook, E.H.; Gallagher, L.; Gill, M.; Hallmayer, J.; Paterson, A.D.; Sutcliffe, J.S.; Szatmari, P.; Vieland, V.J.; Hakonarson, H.; Devlin, B.While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
- Insights into corrosion behaviour of uncoated Mg alloys for biomedical applications in different aqueous mediaPublication . Neves, C.S.; Sousa, I.; Freitas, M.A.; Moreira, L.; Costa, C.; Teixeira, J.P.; Fraga, S.; Pinto, E.; Almeida, A.; Scharnagl, N.; Zheludkevich, M.L.; Ferreira, M.G.S.; Tedim, J.MgCa and MgGd series of alloys are often reported as promising candidates for biomedical applications. In the present study, cytotoxicity and corrosion behavior of Mg1Ca and Mg10Gd alloys in different electrolytes (NaCl, PBS, MEM) have been investigated in order to make a direct comparison and understand the mechanisms behind their performance. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) were employed to analyze corrosion processes depending on media composition, whereas X-Ray diffraction (XRD) and scanning electron microscopy (SEM) were used to evaluate crystalline structure, phase composition and surface morphology of the corroded substrates after immersion in the different electrolytes. Moreover, cytotoxicity of the Mg alloys was assessed using the WST-1 reduction and lactate dehydrogenase (LDH) release assays in L929 mouse fibroblasts. The electrochemical results showed that Mg1Ca has a lower degradation rate when compared to Mg10Gd, due to the lower microgalvanic effects and the presence of Ca as an alloying element. Furthermore, the corrosion activity is reduced in MEM, for both alloys, when compared to NaCl and PBS. The cytotoxicity assays revealed that Mg10Gd was cytotoxic in all the conditions tested, while the toxicity of Mg1Ca was low. Overall, these findings show that Mg1Ca alloy presents a higher corrosion resistance and biocompatibility and is a promising material to be used in biomedical implants.
- New functional ingredients from Salvia sclareoides for the prevention of Alzheimer´s diseasePublication . Abraços, L.; Martins, A.; Neng, N.; Nogueira, J.M.F.; Serralheiro, M.L.; Batista, A.; Raymundo, A.; Sousa, I.; Albuquerque, T.G.; Costa, H.S.; Rauter, A.P.Salvia sclareoides is a plant of spontaneous Portuguese vegetation that has relevant properties, as part of its cholinergic action and in the prevention of the formation of amyloid plaques. Previous studies suggested1,2 that this species of Salvia can be used as a functional food and also in the development of a food supplement in the context of the prevention and treatment of Alzheimer's disease. Salty cookies were developed with the incorporation of different concentrations (2% and 5%) of S. Sclareoides. The nutritional composition of the cookies was determined, namely: fatty acid profile3, moisture content, ash, total protein, total fat3, dietary fibre and salt3. The available carbohydrates and the energetic value were obtained by calculation. Ethanol extracts from the salty cookies were prepared to evaluate the antioxidant (DPPH) and anticholinesterase (Ellman method) activities. Total phenolic content was evaluated by the Folin-Ciocalteu1 method and the phenolic composition was analysed by high performance liquid chromatography with diode array detection. The ethanol extracts of the cookies with 5% of S. sclareoides showed the best acetylcholinesterase inhibition (44.4%), the highest concentration of phenolic compounds (22.78 mg GAE/g dry extract), and antioxidant activity (10.3%). The flavonoids rutin and (7-O-glucosyl)luteolin are clearly the major constituents present in the extracts, along with epicatechin, ellagic acid, and (7-O-glucosyl) naringenin. The incorporation of this plant in the cookies formulation resulted in a pleasant and nutritionally interesting functional product with potential application in the prevention of neurodegenerative diseases.
- A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorderPublication . Casey, J.P.; Magalhaes, T.; Conroy, J.M.; Regan, R.; Shah, N.; Anney, R.; Shields, D.C.; Abrahams, B.S.; Almeida, J.; Bacchelli, E.; Bailey, A.J.; Piven, J.; Posey, D.J.; Poustka, A.; Poustka, F.; Ragoussis, J.; Roge, B.; Rutter, M.L.; Sequeira, A.F.; Soorya, L.; Sousa, I.; Wittemeyer, K.; Sykes, N.; Stoppioni, V.; Tancredi, R.; Tauber, M.; Thompson, A.P.; Thomson, S.; Tsiantis, J.; Van Engeland, H.; Vincent, J.B.; Volkmar, F.; Yaspan, B.L.; Vorstman, J.A.; Wallace, S.; Wang, K.; Wassink, T.H.; White, K.; Wing, K.; Zwaigenbaum, L.; Betancur, C.; Buxbaum, J.D.; Cantor, R.M.; Cook, E.H.; Coon, H.; Cuccaro, M.L.; Geschwind, D.H.; Baird, G.; Haines, J.L.; Hallmayer, J.; Monaco, A.P.; Nurnberger, J.I. Jr; Pericak-Vance, M.A.; Schellenberg, G.D.; Scherer, S.W.; Sutcliffe, J.S.; Szatmari, P.; Vieland, V.J.; Battaglia, A.; Wijsman, E.M.; Green, A.; Gill, M.; Gallagher, L.; Vicente, A.M.; Ennis, S.; Berney, T.; Bolshakova, N.; Bolton, P.F.; Bourgeron, T.; Brennan, S.; Cali, P.; Correia, C.; Corsello, C.; Coutanche, M.; Dawson, G.; de Jonge, M.; Delorme, R.; Duketis, E.; Duque, F.; Estes, A.; Farrar, P.; Fernandez, B.A.; Folstein, S.E.; Foley, S.; Fombonne, E.; Freitag, C.M.; Gilbert, J.; Gillberg, C.; Glessner, J.T.; Green, J.; Guter, S.J.; Hakonarson, H.; Holt, R.; Hughes, G.; Hus, V.; Igliozzi, R.; Kim, C.; Klauck, S.M.; Kolevzon, A.; Lamb, J.A.; Leboyer, M.; Le Couteur, A.; Leventhal, B.L.; Lord, C.; Lund, S.C.; Maestrini, E.; Mantoulan, C.; Marshall, C.R.; McConachie, H.; McDougle, C.J.; McGrath, J.; McMahon, W.M.; Merikangas, A.; Miller, J.; Minopoli, F.; Mirza, G.K.; Munson, J.; Nelson, S.F.; Nygren, G.; Oliveira, G.; Pagnamenta, A.T.; Papanikolaou, K.; Parr, J.R.; Parrini, B.; Pickles, A.; Pinto, D.Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.