| 1. |
- 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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| 2. |
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| 3. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 4. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 5. |
- Castelli Dransart, Dolores Angela, et al.
(författare)
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A systematic review of older adults’ request for or attitude toward euthanasia or assisted-suicide
- 2021
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Ingår i: Aging & Mental Health. - : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 25:3, s. 420-430
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Prevalence rates of death by euthanasia (EUT) and physician-assisted suicide (PAS) have increased among older adults, and public debates on these practices are still taking place. In this context, it seemed important to conduct a systematic review of the predictors (demographic, physical health, psychological, social, quality of life, religious, or existential) associated with attitudes toward, wishes and requests for, as well as death by EUT/PAS among individuals aged 60years and over.Method: The search for quantitative studies in PsycINFO and MEDLINE databases was conducted three times from February 2016 until April 2018. Articles of probable relevance (n=327) were assessed for eligibility. Studies that only presented descriptive data (n=306) were excluded.Results: This review identified 21 studies with predictive analyses, but in only 4 did older adults face actual end-of-life decisions. Most studies (17) investigated attitudes toward EUT/PAS (9 through hypothetical scenarios). Younger age, lower religiosity, higher education, and higher socio-economic status were the most consistent predictors of endorsement of EUT/PAS. Findings were heterogeneous with regard to physical health, psychological, and social factors. Findings were difficult to compare across studies because of the variety of sample characteristics and outcomes measures.Conclusion: Future studies should adopt common and explicit definitions of EUT/PAS, as well as research designs (e.g. mixed longitudinal) that allow for better consideration of personal, social, and cultural factors, and their interplay, on EUT/PAS decisions.
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| 6. |
- Cooper, Ian R., et al.
(författare)
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Discovery and structure-activity relationships of a novel isothiazolone class of bacterial type II topoisomerase inhibitors
- 2016
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier BV. - 0960-894X .- 1464-3405. ; 26:17, s. 4179-4183
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent and unmet medical need for new antibacterial drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. During the course of our wider efforts to discover and exploit novel mechanism of action antibacterials, we have identified a novel series of isothiazolone based inhibitors of bacterial type II topoisomerase. Compounds from the class displayed excellent activity against both Gram-positive and Gram-negative bacteria with encouraging activity against a panel of MDR clinical Escherichia coli isolates when compared to ciprofloxacin. Representative compounds also displayed a promising in vitro safety profile.
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| 7. |
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| 8. |
- Egelhofer, Thea A, et al.
(författare)
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An assessment of histone-modification antibody quality
- 2011
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Ingår i: Nature Structural & Molecular Biology. - : Springer Science and Business Media LLC. - 1545-9993 .- 1545-9985. ; 18:1, s. 91-93
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Tidskriftsartikel (refereegranskat)abstract
- We have tested the specificity and utility of more than 200 antibodies raised against 57 different histone modifications in Drosophila melanogaster, Caenorhabditis elegans and human cells. Although most antibodies performed well, more than 25% failed specificity tests by dot blot or western blot. Among specific antibodies, more than 20% failed in chromatin immunoprecipitation experiments. We advise rigorous testing of histone-modification antibodies before use, and we provide a website for posting new test results (http://compbio.med.harvard.edu/antibodies/).
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| 9. |
- Mellqvist Fässberg, Madeleine, et al.
(författare)
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A systematic review of physical illness, functional disability, and suicidal behaviour among older adults
- 2016
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Ingår i: Aging & Mental Health. - : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 2:20, s. 166-194
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To conduct a systematic review of studies that examined associations between physical illness/functional disability and suicidal behaviour (including ideation, nonfatal and fatal suicidal behaviour) among individuals aged 65 and older. Method: Articles published through November 2014 were identified through electronic searches using the ERIC, Google Scholar, PsycINFO, PubMed, and Scopus databases. Search terms used were suicid0 or death wishes or deliberate self- harm. Studies about suicidal behaviour in individuals aged 65 and older with physical illness/functional disabilities were included in the review. Results: Sixty-five articles (across 61 independent samples) met inclusion criteria. Results from 59 quantitative studies conducted in four continents suggest that suicidal behaviour is associated with functional disability and numerous specific conditions including malignant diseases, neurological disorders, pain, COPD, liver disease, male genital disorders, and arthritis/arthrosis. Six qualitative studies from three continents contextualized these findings, providing insights into the subjective experiences of suicidal individuals. Implications for interventions and future research are discussed. Conclusion: Functional disability, as well as a number of specific physical illnesses, was shown to be associated with suicidal behaviour in older adults. We need to learn more about what at-risk, physically ill patients want, and need, to inform prevention efforts for older adults.
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| 10. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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