| 1. |
- Pocas, Juliana, et al.
(författare)
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Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:20
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Tidskriftsartikel (refereegranskat)abstract
- Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane pro-teoglycan, is highly expressed in intestinal subtype gastric tumors and that this sig -nature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.
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| 2. |
- Sousa, Elsa, et al.
(författare)
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Ankylosing Spondylitis Susceptibility and Severity-Contribution of TNF Gene Promoter Polymorphisms at Positions-238 and-308
- 2009
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Ingår i: Contemporary Challenges in Autoimmunity. - : Wiley. - 0077-8923. ; 1173, s. 581-588
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Konferensbidrag (refereegranskat)abstract
- Ankylosing spondylitis (AS) is a chronic inflammatory disease in which genetic factors play a central role. The efficacy of TNF blockers has reoriented research in this field in order to explain the influence of TNF in AS pathogenesis. The objective of this study was to access the influence of single nucleotide polymorphisms (SNPs) at positions -308 and -238 of the promoter region of TNF gene on AS susceptibility and prognosis. SNPS were determined by restriction fragment length polymorphisms in patients and controls. AS patients exhibited a decreased frequency of the A allele at position -238 (10%) when compared with controls (18%), suggesting that this could be a protective factor for disease susceptibility. In addition, the -308 GA/AA genotypes were associated with later disease onset in AS patients. These results suggest that TNF gene promoter polymorphisms at positions -238 and -308 could have a small influence on AS susceptibility and prognosis.
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| 3. |
- Abraham, Vincent, et al.
(författare)
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Leniency of the Competition Commission of India
- 2022
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Ingår i: SSRN Electronic Journal. - : SSRN. - 1556-5068 .- 1556-5068.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The optimization of fines to deter and detect cartel behavior is one of the main goals of competition policy. Although it is generally argued that fines should be high to be deterrent, the debate on what constitutes an optimal fine is unsettled and some authors suggest using profits (rather than turnover) to calculate "optimal" fines. We exploit data on cartel convictions by the Competition Commission of India (CCI) between 2009 and 2021, which is particularly useful to study this issue as it allows for fines to be calculated using profits or turnover. We examine how much cartel members can “save” in monetary sanctions relative to its legal maximum. In doing so, we also examine the determinants of fines and leniency program reductions for firms, associations and individuals. We find that: (i) using a profit metric leads to larger relative fines; (ii) multiple offenders can save a larger proportion of the fine; and (iii) firms in larger cartels receive lower relative fines. We also show how the cartel type affects the relative savings from fines (RSF); and that fines are far from the legal maximum (thus decreasing the incentive to apply for leniency)
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| 4. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Anney, Richard, et al.
(författare)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Tidskriftsartikel (refereegranskat)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk 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 association of individual SNPs, we also sought evidence that common variants, en masse, might affect 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. By 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 ASD risk but their individual effects are modest.
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| 6. |
- Casey, Jillian P, et al.
(författare)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Coelho, Vera, et al.
(författare)
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Preschool practices in Sweden, Portugal, and the United States
- 2021
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Ingår i: Early Childhood Research Quarterly. - : Elsevier BV. - 0885-2006 .- 1873-7706. ; 55, s. 79-96
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Tidskriftsartikel (refereegranskat)abstract
- Across countries, there are important differences related to the goals, organization, and educational philosophies of care provided to young children prior to formal schooling. Those differences are likely reflected in the classroom practices and teacher-child interactions within a country's early childhood education and care (ECEC) classrooms. This study aims to evaluate the within-country relevance of two classroom observation measures primarily based on a behavioral count approach focused on teacher and child behaviors; and to examine preschool practices in Sweden, Portugal, and the U.S., as they reflect each country's ECEC goals, organization, and educational philosophies. Participants are 78 preschool settings in Sweden, 42 in Portugal, and 168 in the U.S. Results show that the measures targeted culturally-relevant behaviors and provided inter-rater reliability for the behavior count variables in the three countries. Future collaborations may address additional culturally-specific variables. The behavioral descriptions yielded by combining behavioral counts of the measures are analyzed by researchers from the relevant country for insights to the country's values related to early childhood as well as current debates regarding care for children. Measures that provide comprehensive descriptions of classroom settings and apply minimal external or comparative value judgments on the behaviors observed are of practical utility for collaborative international work.
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| 8. |
- Gromicho, Marta, et al.
(författare)
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Frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese patients with amyotrophic lateral sclerosis
- 2018
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 70
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Tidskriftsartikel (refereegranskat)abstract
- Mutation frequency of the 2 main amyotrophic lateral sclerosis (ALS) erelated genes, C9orf72 and SOD1, varies considerably across the world. We analyzed those genes in a large population of Portuguese ALS patients (n = 371) and recorded demographic and clinical features. Familial ALS (FALS) was disclosed in 11.6% of patients. Mutations in either SOD1 or C9orf72 were found in 9.2% of patients and accounted for 40% of FALS and 5.2% of sporadic ALS. SOD1 mutations were rare (0.83%), but a novel and probably disease-causing mutation was identified: p. Ala152Pro (c. 457G>C). The C9orf72 hexanucleotide repeat expansion was the commonest abnormality, accounting for 4.6% of sporadic ALS and 37.5% of FALS; in these patients, Frontotemporal Dementia was prevalent. This first report on the frequency of C9orf72 hexanucleotide repeat expansion and SOD1 mutations in Portuguese ALS patients reiterate that the genetic architecture of ALS varies among different geographic regions. The mutations incidence in ALS patients (w10%) and associated phenotypes suggest that genetic tests should be offered to more patients, and other genes should be investigated in our population.
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| 9. |
- Leitao, Jorge, et al.
(författare)
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Prevalence and risk factors of fatty liver in Portuguese adults
- 2020
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Ingår i: European Journal of Clinical Investigation. - : WILEY. - 0014-2972 .- 1365-2362. ; 50:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Prevalence of fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) depends mainly on obesity, diabetes and genetic factors. FL and NAFLD prevalence was evaluated in Portuguese adult population and correlated with several risk factors and related mortality data, within the same period. Materials and methods A cross-sectional, population-based multicenter study, voluntary and randomly selected in 834 Portuguese adults (18-79 years). Participants were evaluated after 12-hour fasting. Anthropometric data, past history including alcohol consumption, and associated diseases were registered. Blood samples were collected for biochemical testing. Dietary intake was evaluated using a semi-quantitative food frequency questionnaire. Presence of FL was evaluated using ultrasound, and NAFLD was diagnosed after exclusion of other causes for liver disease. Results Adjusted prevalence of FL and NAFLD was 37.8% and 17.0%, respectively. FL individuals were older, more frequently males, with increased probability of having obesity, diabetes or harmful alcohol consumption (HAC). NAFLD individuals were also older, but had a similar sex distribution and an increased probability of obesity and diabetes. In both groups, no differences were found regarding dietary pattern or physical activity. During the same time period, nonalcoholic steatohepatitis (NASH) liver-related deaths in Portugal were 0.105/100 000, while alcohol-related liver disease mortality was 6.790/100 000. Conclusion The large spectrum of FL was present in more than one third of the population, although only less than half could be classified as NAFLD. Other significant risk factors, such as HAC, are probably implicated in FL, explaining the low NASH-related mortality compared with the high alcohol-related mortality during the same time period.
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| 10. |
- Lindblad, Peter, et al.
(författare)
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CyanoFactory, a European consortium to develop technologies needed to advance cyanobacteria as chassis for production of chemicals and fuels
- 2019
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Ingår i: Algal Research. - : Elsevier. - 2211-9264. ; 41
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Forskningsöversikt (refereegranskat)abstract
- CyanoFactory, Design, construction and demonstration of solar biofuel production using novel (photo) synthetic cell factories, was an R&D project developed in response to the European Commission FP7-ENERGY-2012-1 call "Future Emerging Technologies" and the need for significant advances in both new science and technologies to convert solar energy into a fuel. CyanoFactory was an example of "purpose driven" research and development with identified scientific goals and creation of new technologies. The present overview highlights significant outcomes of the project, three years after its successful completion. The scientific progress of CyanoFactory involved: (i) development of a ToolBox for cyanobacterial synthetic biology; (ii) construction of DataWarehouse/Bioinformatics web-based capacities and functions; (iii) improvement of chassis growth, functionality and robustness; (iv) introduction of custom designed genetic constructs into cyanobacteria, (v) improvement of photosynthetic efficiency towards hydrogen production; (vi) biosafety mechanisms; (vii) analyses of the designed cyanobacterial cells to identify bottlenecks with suggestions on further improvements; (viii) metabolic modelling of engineered cells; (ix) development of an efficient laboratory scale photobioreactor unit; and (x) the assembly and experimental performance assessment of a larger (1350 L) outdoor flat panel photobioreactor system during two seasons. CyanoFactory - Custom design and purpose construction of microbial cells for the production of desired products using synthetic biology - aimed to go beyond conventional paths to pursue innovative and high impact goals. CyanoFactory brought together ten leading European partners (universities, research organizations and enterprises) with a common goal - to develop the future technologies in Synthetic biology and Advanced photobioreactors.
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