Advances in the molecular biology of medulloblastoma revealed four genetically and clinically dis... more Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group...
Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood canc... more Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Transcriptional analyses id...
The wide variability of responses to corticotherapy suggests a role for individual recognition of... more The wide variability of responses to corticotherapy suggests a role for individual recognition of steroid sensitivity in order to customize treatment. Oral dexamethasone (DEX) administration may be hindered by the rate of its intestinal absorption and the liver first-passage effect. In this study we suggest that an intravenous very low dose DEX suppression test (VLD IV-DST) can be used as an index for glucocorticoid (GC) sensitivity. We evaluated 87 normal subjects: 44 prepubertal children, 23 adolescents and 20 adults with a VLD IV-DST using 20 mug/m(2) of DEX (dose able to recognize GC sensitivity). Cortisol was initially measured at several time-points after DEX prompting us to establish its nadir and subsequent simplification of the test by measuring cortisol at baseline and after 120 min. Baseline cortisol was similar in adolescents and in adults, but lower in children. There was a spectrum of individual responses in all age groups. The percent reduction of cortisol after 120 m...
Medulloblastoma comprises four molecular subgroups of which Group 3 medulloblastoma is characteri... more Medulloblastoma comprises four molecular subgroups of which Group 3 medulloblastoma is characterized by MYC amplification and MYC overexpression. Lymphoma cells expressing high levels of MYC are susceptible to apoptosis following treatment with inhibitors of mitosis. One of the key regulatory kinases involved in multiple stages of mitosis is Aurora kinase B. We hypothesized that medulloblastoma cells that overexpress MYC would be uniquely sensitized to the apoptotic effects of Aurora B inhibition. The specific inhibition of Aurora kinase B was achieved in MYC- overexpressing medulloblastoma cells with AZD1152-HQPA. MYC overexpression sensitized medulloblastoma cells to cell death upon Aurora B inhibition. This process was found to be independent of endoreplication. Using both flank and intracranial cerebellar xenografts we demonstrate that tumors formed from MYC-overexpressing medulloblastoma cells show a response to Aurora B inhibition including growth impairment and apoptosis indu...
The full developmental embryonic sequence of Gobius cruentatus is described for the ¢rst time. Em... more The full developmental embryonic sequence of Gobius cruentatus is described for the ¢rst time. Embryonic development lasted 13 days (14.0^15.08C). The newly hatched larvae (3.3mm total length) presented pigmented eyes, the yolk is fully absorbed, and the mouth and ...
- Compreensão dos principais paradigmas na investigação em educação; - Compreensão da natureza e ... more - Compreensão dos principais paradigmas na investigação em educação; - Compreensão da natureza e características do processo investigativo, das suas etapas e componentes; - Compreensão dos critérios para a apreciação de um processo de investigação e do valor dos seus ...
VA. Early ontogeny of Lipophrys pholis 203 ABSTRACT Information on the early ontogeny of Lipophry... more VA. Early ontogeny of Lipophrys pholis 203 ABSTRACT Information on the early ontogeny of Lipophrys pholis is scattered and incomplete. In this paper we describe for the first time the full developmental sequence from egg to juvenile in controlled conditions. In addition, some ...
Page 1. Revista da Educação, Vol. XVII, nº 1, 2010 | 83 - 95 83 D. CARLOS DE BRAGANÇA, UM REI QUE... more Page 1. Revista da Educação, Vol. XVII, nº 1, 2010 | 83 - 95 83 D. CARLOS DE BRAGANÇA, UM REI QUE SE TORNOU PIONEIRO DA OCEANOGRAFIA EM PORTUGAL: RECURSOS PARA O ENSINO DAS CIÊNCIAS Cláudia ...
The main objective of this study was to understand the impacts of a science teacher training cour... more The main objective of this study was to understand the impacts of a science teacher training course, designed and implemented in a science centre, in teachers’ exploitation of the opportunities inherent to science centres learning contexts, through the evaluation of its impact. Data were collected through direct observation of the tutorial sessions and the school-visits organized and implemented by seven teachers. An online questionnaire was administered to 38 participants in order to understand their perspectives of the course. The data were triangulated in order to make an evaluation of the course according to its effectiveness, efficiency, relevance and durability. Data showed that the development of a science teacher course by a science centre, proved to help teachers to capitalize on the opportunities these non-formal institutions offer to enrich and reinforce science school learning. Some improvements were suggested in order to achieve a greater effectiveness.
Advances in the molecular biology of medulloblastoma revealed four genetically and clinically dis... more Advances in the molecular biology of medulloblastoma revealed four genetically and clinically distinct subgroups. Group 3 medulloblastomas are characterized by frequent amplifications of the oncogene MYC, a high incidence of metastasis, and poor prognosis despite aggressive therapy. We investigated several potential small molecule inhibitors to target Group 3 medulloblastomas based on gene expression data using an in silico drug screen. The Connectivity Map (C-MAP) analysis identified piperlongumine as the top candidate drug for non-WNT medulloblastomas and the cyclin-dependent kinase (CDK) inhibitor alsterpaullone as the compound predicted to have specific antitumor activity against Group 3 medulloblastomas. To validate our findings we used these inhibitors against established Group 3 medulloblastoma cell lines. The C-MAP predicted drugs reduced cell proliferation in vitro and increased survival in Group 3 medulloblastoma xenografts. Alsterpaullone had the highest efficacy in Group...
Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood canc... more Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Transcriptional analyses id...
The wide variability of responses to corticotherapy suggests a role for individual recognition of... more The wide variability of responses to corticotherapy suggests a role for individual recognition of steroid sensitivity in order to customize treatment. Oral dexamethasone (DEX) administration may be hindered by the rate of its intestinal absorption and the liver first-passage effect. In this study we suggest that an intravenous very low dose DEX suppression test (VLD IV-DST) can be used as an index for glucocorticoid (GC) sensitivity. We evaluated 87 normal subjects: 44 prepubertal children, 23 adolescents and 20 adults with a VLD IV-DST using 20 mug/m(2) of DEX (dose able to recognize GC sensitivity). Cortisol was initially measured at several time-points after DEX prompting us to establish its nadir and subsequent simplification of the test by measuring cortisol at baseline and after 120 min. Baseline cortisol was similar in adolescents and in adults, but lower in children. There was a spectrum of individual responses in all age groups. The percent reduction of cortisol after 120 m...
Medulloblastoma comprises four molecular subgroups of which Group 3 medulloblastoma is characteri... more Medulloblastoma comprises four molecular subgroups of which Group 3 medulloblastoma is characterized by MYC amplification and MYC overexpression. Lymphoma cells expressing high levels of MYC are susceptible to apoptosis following treatment with inhibitors of mitosis. One of the key regulatory kinases involved in multiple stages of mitosis is Aurora kinase B. We hypothesized that medulloblastoma cells that overexpress MYC would be uniquely sensitized to the apoptotic effects of Aurora B inhibition. The specific inhibition of Aurora kinase B was achieved in MYC- overexpressing medulloblastoma cells with AZD1152-HQPA. MYC overexpression sensitized medulloblastoma cells to cell death upon Aurora B inhibition. This process was found to be independent of endoreplication. Using both flank and intracranial cerebellar xenografts we demonstrate that tumors formed from MYC-overexpressing medulloblastoma cells show a response to Aurora B inhibition including growth impairment and apoptosis indu...
The full developmental embryonic sequence of Gobius cruentatus is described for the ¢rst time. Em... more The full developmental embryonic sequence of Gobius cruentatus is described for the ¢rst time. Embryonic development lasted 13 days (14.0^15.08C). The newly hatched larvae (3.3mm total length) presented pigmented eyes, the yolk is fully absorbed, and the mouth and ...
- Compreensão dos principais paradigmas na investigação em educação; - Compreensão da natureza e ... more - Compreensão dos principais paradigmas na investigação em educação; - Compreensão da natureza e características do processo investigativo, das suas etapas e componentes; - Compreensão dos critérios para a apreciação de um processo de investigação e do valor dos seus ...
VA. Early ontogeny of Lipophrys pholis 203 ABSTRACT Information on the early ontogeny of Lipophry... more VA. Early ontogeny of Lipophrys pholis 203 ABSTRACT Information on the early ontogeny of Lipophrys pholis is scattered and incomplete. In this paper we describe for the first time the full developmental sequence from egg to juvenile in controlled conditions. In addition, some ...
Page 1. Revista da Educação, Vol. XVII, nº 1, 2010 | 83 - 95 83 D. CARLOS DE BRAGANÇA, UM REI QUE... more Page 1. Revista da Educação, Vol. XVII, nº 1, 2010 | 83 - 95 83 D. CARLOS DE BRAGANÇA, UM REI QUE SE TORNOU PIONEIRO DA OCEANOGRAFIA EM PORTUGAL: RECURSOS PARA O ENSINO DAS CIÊNCIAS Cláudia ...
The main objective of this study was to understand the impacts of a science teacher training cour... more The main objective of this study was to understand the impacts of a science teacher training course, designed and implemented in a science centre, in teachers’ exploitation of the opportunities inherent to science centres learning contexts, through the evaluation of its impact. Data were collected through direct observation of the tutorial sessions and the school-visits organized and implemented by seven teachers. An online questionnaire was administered to 38 participants in order to understand their perspectives of the course. The data were triangulated in order to make an evaluation of the course according to its effectiveness, efficiency, relevance and durability. Data showed that the development of a science teacher course by a science centre, proved to help teachers to capitalize on the opportunities these non-formal institutions offer to enrich and reinforce science school learning. Some improvements were suggested in order to achieve a greater effectiveness.
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