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Sökning: WFRF:(Salomoni P)

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  • 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.
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  • Gerber, Julia P., et al. (författare)
  • Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation
  • 2021
  • Ingår i: Nature Cell Biology. - : Springer Science and Business Media LLC. - 1465-7392 .- 1476-4679. ; 23:12, s. 1224-1239
  • Tidskriftsartikel (refereegranskat)abstract
    • Defective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.3 chaperone Daxx, a retrotransposable element repressor inactivated in myeloid leukaemia and other neoplasms, in protection from inflammatory disease. Loss of Daxx alters the chromatin landscape, H3.3 distribution and histone marks of haematopoietic progenitors, leading to engagement of a Pu.1-dependent transcriptional programme for myelopoiesis at the expense of B-cell differentiation. This causes neutrophilia and inflammation, predisposing mice to develop an autoinflammatory skin disease. While these molecular and phenotypic perturbations are in part reverted in animals lacking both Pu.1 and Daxx, haematopoietic progenitors in these mice show unique chromatin and transcriptome alterations, suggesting an interaction between these two pathways. Overall, our findings implicate retrotransposable element silencing in haematopoiesis and suggest a cross-talk between the H3.3 loading machinery and the pioneer transcription factor Pu.1.
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  • Röijezon, Ulrik, et al. (författare)
  • Deep and superficial cervical muscles respond differently to unstable motor skill tasks
  • 2021
  • Ingår i: Human Movement Science. - : Elsevier. - 0167-9457 .- 1872-7646. ; 80
  • Tidskriftsartikel (refereegranskat)abstract
    • Biomechanical modelling and physiological studies suggest that various spinal muscle layers differ in their contribution to spine movement and stiffness. This study aimed to investigate the activation of deep and superficial muscles in stable and unstable task conditions. Nine healthy participants performed a task of controlling a metal ball on a plate fixed to the head in seated position. In unstable tasks, visual feedback was provided by mirrors to move the ball to the centre of the plate by small head movements and maintain the position for 3 s. Task difficulty was adjusted in a stepwise progression of difficulty using five surfaces with materials of decreasing resistance. In the stable condition, the ball was fixed to the plate's centre. EMG was recorded with surface (sternocleidomastoid, anterior scalenes, upper trapezius) and fine-wire electrodes (rectus capitis posterior major, obliquus inferior, multifidus, semispinalis cervicis, splenius capitis). The outcome variable was root mean square (RMS) EMG during the part of the task when the ball was maintained in the centre position. Results revealed greater cervical muscle activity in the unstable than stable conditions (p < 0.001, ηp2 = 0.746). Control of deep and superficial cervical muscles differed (p = 0.003, ηp2 = 0.354). Deep cervical muscle activity was greater with unstable tasks, but did not differ with task difficulty. In contrast, superficial cervical muscle activity increased in a stepwise manner with increasing challenge. These results support the notion that the central nervous system uses different strategies for control of deep versus superficial muscle layers of the cervical spine in association with instability.
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