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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Archambault, Alexi N., et al.
(författare)
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Cumulative Burden of Colorectal Cancer Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 0016-5085 .- 1528-0012. ; 158:5, s. 1274-1286.e12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 x 10(-5)). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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| 5. |
- Ferreira, Marisa Borges, et al.
(författare)
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Relationships between neuropsychological and antisaccade measures in multiple sclerosis patients
- 2018
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Ingår i: PeerJ. - : PeerJ, Inc. - 2167-8359. ; 6, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe Stroop test is frequently used to assess deficits in inhibitory control in people with multiple sclerosis (MS). This test has limitations and antisaccade eye movements, that also measure inhibitory control, may be an alternative to Stroop.ObjectivesThe aim of this study was twofold: (i) to investigate if the performance in the antisaccade task is altered in patients with MS and (ii) to investigate the correlation between performances in neuropsychological tests, the Stroop test and the antisaccade task.MethodsWe measured antisaccades (AS) parameters with an infrared eye tracker (SMIRED 250 Hz) using a standard AS paradigm. A total of 38 subjects diagnosed with MS and 38 age and gender matched controls participated in this study. Neuropsychological measures were obtained from the MS group.ResultsPatients with MS have higher error rates and prolonged latency than controls in the antisaccade task. There was a consistent association between the Stroop performance and AS latency. Stroop performance but not AS latency was associated with other neuropsychological measures in which the MS group showed deficits.ConclusionsOur findings suggest that AS may be a selective and independent measure to investigate inhibitory control in patients with MS. More studies are necessary to confirm our results and to describe brain correlates associated with impaired performance in the antisaccade task in people diagnosed with MS.
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| 6. |
- Macedo, António Filipe, et al.
(författare)
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Anti-saccades in early stages of multiple sclerosis
- 2015
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Ingår i: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 56:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Eye movements disability is common finding in multiple sclerosis (MS) but the exact stage at which changes are visible is not clear. The aim of study was to assess if anti-saccade (AS) planning and execution are altered at early stages of the disease.Methods: A total of 48 participants with MS selected by a neurologist (JJC) at Hospital de Braga and 52 controls participated in this study. Inclusion criteria: relapsing-remitting course, EDSS≤3, 1 month or more without MS crisis, and normal or corrected visual acuity. Exclusion criteria (MS and Control): cognitive impairment, traumatic brain injury or stroke. The mean age in the MS group was 37y and 33y in the control group. Eye movements were monitored using a binocular infrared eyetracker running at 250Hz(RED250, SMI Gmb Germany), precision <0.4deg, stimuli were presented in a 22 monitor (Dell P2210). Code for running the experiment and data analysis was written using the Matlab (Mathworks Inc). Participants were seated in a room dim light at 74cm from the monitor and head movements were minimized by a headband. The task was to fixate, after a variable period between steady fixation and the stimulus of 1250ms or 1600ms, participants looked as quickly as possible for the opposite direction where the target (a 30x30mm cross) was presented (anti-saccade movement). Each subject performed 40 trails.Results: The main results were the proportion of the directional errors (wherein the participant voluntarily looked for the wrong side), and latencies for: i) anti-saccades, ii) pro-saccades (movement in the same direction of the stimulus) and iii) correction (reaction time that the participant takes from the error fixation until to start the movement). The mean number of errors was 28%(SD=19) in MS group and 16%(SD=11) in the control group, mean difference 12%, t(74)=3.83, p<.001. Anti-saccades latency was 330msec (SD=61) in the MS group and 294ms(SD=59) in the control group, mean difference 36ms, F(1,98)=10.99, p<.05. The mean of the correction latency value was 178ms(SD=111) in the MS group and 129ms(SD=107) in the control group with a mean difference of 49ms, F(1,98)=6, p<.05. No statistically significant differences were found in accuracy and pro-saccade latency between groups.Conclusions: This study shows that anti-saccades latency and errors are increased at early stages of multiple sclerosis. Anti-saccades might be a sensitive tool to assess functional status in people with this condition.
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| 7. |
- Papadimitriou, Nikos, et al.
(författare)
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Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis
- 2020
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value=0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value=0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers. Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.
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| 8. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 9. |
- Antanas, Laura, et al.
(författare)
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Semantic and geometric reasoning for robotic grasping : a probabilistic logic approach
- 2019
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Ingår i: Autonomous Robots. - : Springer. - 0929-5593 .- 1573-7527. ; 43:6, s. 1393-1418
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Tidskriftsartikel (refereegranskat)abstract
- While any grasp must satisfy the grasping stability criteria, good grasps depend on the specific manipulation scenario: the object, its properties and functionalities, as well as the task and grasp constraints. We propose a probabilistic logic approach for robot grasping, which improves grasping capabilities by leveraging semantic object parts. It provides the robot with semantic reasoning skills about the most likely object part to be grasped, given the task constraints and object properties, while also dealing with the uncertainty of visual perception and grasp planning. The probabilistic logic framework is task-dependent. It semantically reasons about pre-grasp configurations with respect to the intended task and employs object-task affordances and object/task ontologies to encode rules that generalize over similar object parts and object/task categories. The use of probabilistic logic for task-dependent grasping contrasts with current approaches that usually learn direct mappings from visual perceptions to task-dependent grasping points. The logic-based module receives data from a low-level module that extracts semantic objects parts, and sends information to the low-level grasp planner. These three modules define our probabilistic logic framework, which is able to perform robotic grasping in realistic kitchen-related scenarios.
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| 10. |
- Barbudo Carrasco, Lais, 1988-
(författare)
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Integração de conteúdos culturais heterogêneos em ambientes digitais do patrimônio cultural : harmonização de modelos conceituais
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Em decorrência da rápida difusão de informação em ambientes web, o acesso e a recuperação da informação de sistemas heterogêneos integrados estão se tornando cada vez mais relevantes. O problema de pesquisa circundante é que os acervos digitais de patrimônio cultural, contidos, por exemplo, em bibliotecas, arquivos e museus – utilizam diferentes padrões o que dificultam a integração entre eles. Diante desta premissa, tem-se a seguinte pergunta de pesquisa: é possível desenvolver uma harmonização de modelos conceituais existentes do patrimônio cultural, na perspectiva da integração de conteúdos culturais heterogêneos em ambientes digitais? Assim, a pesquisa propõe o desenvolvimento de uma harmonização de modelos conceituais para a integração de conteúdos culturais heterogêneos digitais de acervos de arquivos, bibliotecas e museus. O objetivo geral desta pesquisa é desenvolverum processo de harmonização de modelos conceituais do patrimônio cultural, na perspectiva da integração de conteúdos culturais heterogêneos em ambientes digitais. A pesquisa é de natureza, teórica e aplicada, e também classificada como exploratória. Alguns projetos e iniciativas internacionais são analisados: CIDOC CRM do ICOM (Modelo de Referência Conceitual), FRBR da IFLA (Requisitos Funcionais para Registros Bibliográficos), RiC da ICA (Modelo de Descrição Arquivística Records in Contexts), EDM da Europeana (Modelo de Dados da Europeana) e o CRMgeo do OCG (Modelo de Descrição Geoespacial). A tese da pesquisa consiste em afirmar que a harmonização dos modelos conceituais do patrimônio cultural possibilita a integração de conteúdos culturais heterogêneos em ambientes digitais. Os resultados apresentam um processo de harmonização de modelos conceituais do patrimônio cultural mediante um mapeamento terminológico-conceitual, delineamento de categorias e as correspondências das entidades de tais modelos. Portanto, aharmonização dos modelos conceituais possibilita integrar sistemas heterogêneos de acervos de arquivos, bibliotecas e museus em ambientes digitais, proporcionando aos usuários destes ambientes, uma recuperação de conteúdos culturais contextualizados, com caráter dinâmico e semântico, por meio da ampliação dos dados culturais.
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