| 1. |
|
|
| 2. |
|
|
| 3. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
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.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Klionsky, Daniel J., et al.
(författare)
-
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
-
Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
-
Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is 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 verify an autophagic response.
|
|
| 7. |
- Buch, S., et al.
(författare)
-
Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study
- 2023
-
Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 72:2, s. 381-391
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Design Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Results Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41x10(-9), OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94x10(-5), OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12x10(-44)). Conclusion This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
|
|
| 8. |
- Leebens-Mack, James H., et al.
(författare)
-
One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
-
Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
|
|
| 9. |
- Goncalves-Pereira, M, et al.
(författare)
-
[Needs for Care and Service Use in Dementia: Baseline Assessment of Portuguese Participants in the Actifcare Cohort Study]
- 2019
-
Ingår i: Acta medica portuguesa. - : Ordem dos Medicos. - 1646-0758 .- 0870-399X. ; 32:5, s. 355-367
-
Tidskriftsartikel (refereegranskat)abstract
- Introdução: As pessoas com demência e os seus familiares deveriam ter acesso atempado a cuidados formais na comunidade (centros de dia, apoio domiciliário). O projecto EU-Actifcare investigou o acesso/utilização destes serviços em países europeus. Descrevemos a implementação do estudo de coorte e a avaliação inicial em Portugal, com foco nas necessidades de cuidados e recurso aos serviços.Material e Métodos: Selecionámos uma amostra de conveniência de 66 pessoas com diagnóstico de demência ligeira a moderada (residindo na comunidade sem cuidados formais relevantes) e respetivos familiares-cuidadores. A avaliação (clínico-funcional e social) incluiu os instrumentos Camberwell Assessment of Need for the Elderly e Resource Utilization in Dementia.Resultados: Identificámos necessidades não-cobertas dos doentes (média 1,1; DP = 1,7), principalmente de companhia (23% dos casos), sofrimento psicológico (20%) e atividades diárias (14%). Os familiares-cuidadores dedicavam 150 minutos/dia (mediana) à prestação de cuidados e 44% apresentavam necessidades não-cobertas de sofrimento psicológico. Quando havia problemas de acesso/utilização dos serviços de saúde e sociais na comunidade, estes estavam frequentemente relacionados com recusa ou desconhecimento de utentes/familiares.Discussão: A seleção dos participantes não foi fácil, pela especificidade dos critérios adotados. Não almejando representatividade nacional, recrutámos uma amostra típica de pessoas em estádios ligeiros a moderados de demência, em serviços e regiões diferentes. Nalguns casos, encontrámos necessidades não-cobertas e repercussões familiares que já justificariam respostas de serviços na comunidade, não fossem os problemas de acesso/utilização.Conclusão: Na área das demências, existem dificuldades no acesso atempado e utilização efectiva de cuidados formais, coexistindo com uma cobertura menor de necessidades específicas.
|
|
| 10. |
|
|
