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- Galluzzi, L, et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes.
- 2009
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Ingår i: Cell death and differentiation. - : Springer Science and Business Media LLC. - 1476-5403 .- 1350-9047. ; 16:8, s. 1093-107
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Forskningsöversikt (refereegranskat)abstract
- Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate. Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls. These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise. Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells.
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- Sandri, M, et al.
(författare)
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Signalling pathways regulating muscle mass in ageing skeletal muscle : The role of the IGF1-Akt-mTOR-FoxO pathway
- 2013
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Ingår i: Biogerontology (Dordrecht). - : Springer Science and Business Media LLC. - 1389-5729 .- 1573-6768. ; 14:3 SI, s. 303-323
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Tidskriftsartikel (refereegranskat)abstract
- During ageing skeletal muscles undergo a process of structural and functional remodelling that leads to sarcopenia, a syndrome characterized by loss of muscle mass and force and a major cause of physical frailty. To determine the causes of sarcopenia and identify potential targets for interventions aimed at mitigating ageing-dependent muscle wasting, we focussed on the main signalling pathway known to control protein turnover in skeletal muscle, consisting of the insulin-like growth factor 1 (IGF1), the kinase Akt and its downstream effectors, the mammalian target of rapamycin (mTOR) and the transcription factor FoxO. Expression analyses at the transcript and protein level, carried out on well-characterized cohorts of young, old sedentary and old active individuals and on mice aged 200, 500 and 800 days, revealed only modest age-related differences in this pathway. Our findings suggest that during ageing there is no downregulation of IGF1/Akt pathway and that sarcopenia is not due to FoxO activation and upregulation of the proteolytic systems. A potentially interesting result was the increased phosphorylation of the ribosomal protein S6, indicative of increased activation of mTOR complex1 (mTORC1), in aged mice. This result may provide the rationale why rapamycin treatment and caloric restriction promote longevity, since both interventions blunt activation of mTORC1; however, this change was not statistically significant in humans. Finally, genetic perturbation of these pathways in old mice aimed at promoting muscle hypertrophy via Akt overexpression or preventing muscle loss through inactivation of the ubiquitin ligase atrogin1 were found to paradoxically cause muscle pathology and reduce lifespan, suggesting that drastic activation of the IGF1-Akt pathway may be counterproductive, and that sarcopenia is accelerated, not delayed, when protein degradation pathways are impaired.
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- Gaidos, E., et al.
(författare)
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Zodiacal exoplanets in time (ZEIT) - II. A 'super-Earth' orbiting a young K dwarf in the Pleiades Neighbourhood
- 2017
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 464:1, s. 850-862
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Tidskriftsartikel (refereegranskat)abstract
- We describe a 'super-Earth'-size (2.30 +/- 0.16 R-circle plus)planet transiting an early K-type dwarf star in the Campaign 4 field observed by the K2 mission. The host star, EPIC 210363145, was identified as a candidate member of the approximately 120 Myr-old Pleiades cluster based on its kinematics and photometric distance. It is rotationally variable and exhibits near-ultraviolet emission consistent with a Pleiades age, but its rotational period is approximate to 20 d and its spectrum contains no H alpha emission nor the Li I absorption expected of Pleiades K dwarfs. Instead, the star is probably an interloper that is unaffiliated with the cluster, but younger (less than or similar to 1.3 Gyr) than the typical field dwarf. We ruled out a false positive transit signal produced by confusion with a background eclipsing binary by adaptive optics imaging and a statistical calculation. Doppler radial velocity measurements limit the companion mass to <2 times that of Jupiter. Screening of the light curves of 1014 potential Pleiades candidate stars uncovered no additional planets. An injection-and-recovery experiment using the K2 Pleiades light curves with simulated planets, assuming a planet population like that in the Kepler prime field, predicts only 0.8-1.8 detections (versus similar to 20 in an equivalent Kepler sample). The absence of Pleiades planet detections can be attributed to the much shorter monitoring time of K2 (80 d versus 4 yr), increased measurement noise due to spacecraft motion, and the intrinsic noisiness of the stars.
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