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- 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. |
- Fontenelle, LF, et al.
(författare)
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A transdiagnostic perspective of constructs underlying obsessive-compulsive and related disorders: An international Delphi consensus study
- 2020
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Ingår i: The Australian and New Zealand journal of psychiatry. - : SAGE Publications. - 1440-1614 .- 0004-8674. ; 54:7, s. 719-731
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Tidskriftsartikel (refereegranskat)abstract
- The Research Domain Criteria seeks to bridge knowledge from neuroscience with clinical practice by promoting research into valid neurocognitive phenotypes and dimensions, irrespective of symptoms and diagnoses as currently conceptualized. While the Research Domain Criteria offers a vision of future research and practice, its 39 functional constructs need refinement to better target new phenotyping efforts. This study aimed to determine which Research Domain Criteria constructs are most relevant to understanding obsessive-compulsive and related disorders, based on a consensus between experts in the field of obsessive-compulsive and related disorders.Methods:Based on a modified Delphi method, 46 experts were recruited from Australia, Africa, Asia, Europe and the Americas. Over three rounds, experts had the opportunity to review their opinion in light of feedback from the previous round, which included how their response compared to other experts and a summary of comments given.Results:Thirty-four experts completed round one, of whom 28 (82%) completed round two and 24 (71%) completed round three. At the final round, four constructs were endorsed by ⩾75% of experts as ‘primary constructs’ and therefore central to understanding obsessive-compulsive and related disorders. Of these constructs, one came from the Positive Valence System (Habit), two from the Cognitive Control System (Response Selection/Inhibition and Performance Monitoring) and the final construct was an additional item suggested by experts (Compulsivity).Conclusion:This study identified four Research Domain Criteria constructs that, according to experts, cut across different obsessive-compulsive and related disorders. These constructs represent key areas for future investigation, and may have potential implications for clinical practice in terms of diagnostic processes and therapeutic management of obsessive-compulsive and related disorders.
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| 5. |
- Dell'Osso, L, et al.
(författare)
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Temperamental and genetic predictors of suicide attempt and self-mutilation
- 2013
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Ingår i: Neuropsychobiology. - : S. Karger AG. - 1423-0224 .- 0302-282X. ; 68:4, s. 250-257
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background and Aims:</i></b> Literature findings mainly support the notion that suicide attempts (SA) and self-mutilating behavior (SMB) are distinct behaviors, although they may share common psychopathological features. In the present paper we aimed to identify behavioral phenotypes in patients with SA, SMB, or both (SAM) and to analyze the association with candidate genes. <b><i>Methods:</i></b> One hundred forty-two inpatients with a history of SA (n = 86), SMB (n = 22), and SAM (n = 39) were included in this study. Subjects were evaluated using the Tridimensional Personality Questionnaire (TPQ) and the Buss-Durkee Hostility Inventory (BDHI). Polymorphisms within serotonin transporter (SLC6A4, HTTLPR), catechol-O-methyl transferase (COMT, Val158Met), and tryptophan hydroxylase (TPH, 218C>A) were also analyzed. <b><i>Results:</i></b> Principal component factor analysis including the BDHI and TPQ produced 3 factors that could classify the 3 groups of patients with good sensitivity. However, only the ‘pure suicidal' factor had a sufficient positive predictive value. This factor was characterized by high levels of persistence (PS) and, to a lower extent, reward dependence. The distribution of genotypes was not different across patient groups for all polymorphisms, but the SS genotype of HTTLPR was significantly associated with the ‘self-mutilation' factor, characterized by high levels of hostile traits, novelty seeking, and harm avoidance. <b><i>Conclusion:</i></b> The results of the present study suggest that different and overlapping temperamental traits in suicidal and self-mutilating patients are present, although only high levels of PS could predict SA repetition. Finally, HTTLPR may mediate the risk for SMB through modulation of some temperamental traits.
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