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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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- 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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| 9. |
- Kootar, S., et al.
(författare)
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Validation of the CogDrisk Instrument as Predictive of Dementia in Four General Community-Dwelling Populations
- 2023
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Ingår i: The Journal of Prevention of Alzheimer's Disease. - : SERDI. - 2274-5807 .- 2426-0266. ; :10, s. 478-487
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lack of external validation of dementia risk tools is a major limitation for generalizability and translatability of prediction scores in clinical practice and research.Objectives: We aimed to validate a new dementia prediction risk tool called CogDrisk and a version, CogDrisk-AD for predicting Alzheimer’s disease (AD) using cohort studies.Design, Setting, Participants and Measurements: Four cohort studies were identified that included majority of the dementia risk factors from the CogDrisk tool. Participants who were free of dementia at baseline were included. The predictors were component variables in the CogDrisk tool that include self-reported demographics, medical risk factors and lifestyle habits. Risk scores for Any Dementia and AD were computed and Area Under the Curve (AUC) was assessed. To examine modifiable risk factors for dementia, the CogDrisk tool was tested by excluding age and sex estimates from the model.Results: The performance of the tool varied between studies. The overall AUC and 95% CI for predicting dementia was 0.77 (0.57, 0.97) for the Swedish National study on Aging and Care in Kungsholmen, 0.76 (0.70, 0.83) for the Health and Retirement Study - Aging, Demographics and Memory Study, 0.70 (0.67,0.72) for the Cardiovascular Health Study Cognition Study, and 0.66 (0.62,0.70) for the Rush Memory and Aging Project.Conclusions: The CogDrisk and CogDrisk-AD performed well in the four studies. Overall, this tool can be used to assess individualized risk factors of dementia and AD in various population settings.
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| 10. |
- Mann, Andrew W., et al.
(författare)
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Zodiacal Exoplanets In Time (Zeit). III. A Short-Period Planet Orbiting A Pre-Main-Sequence Star In The Upper Scorpius Ob Association
- 2016
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 152:3
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Tidskriftsartikel (refereegranskat)abstract
- We confirm and characterize a close-in (P-orb = 5.425 days), super-Neptune sized (5.04(-0.37)(+0.34) R-circle plus) planet transiting K2-33 (2MASS J16101473-1919095), a late-type (M3) pre-main-sequence (11 Myr old) star in the Upper Scorpius subgroup of the Scorpius-Centaurus OB association. The host star has the kinematics of a member of the Upper Scorpius OB association, and its spectrum contains lithium absorption, an unambiguous sign of youth (<20 Myr) in late-type dwarfs. We combine photometry from K2 and the ground-based MEarth project to refine the planet's properties and constrain the host star's density. We determine K2-33's bolometric flux and effective temperature from moderate-resolution spectra. By utilizing isochrones that include the effects of magnetic fields, we derive a precise radius (6%-7%) and mass (16%) for the host star, and a stellar age consistent with the established value for Upper Scorpius. Follow-up high-resolution imaging and Doppler spectroscopy confirm that the transiting object is not a stellar companion or a background eclipsing binary blended with the target. The shape of the transit, the constancy of the transit depth and periodicity over 1.5 yr, and the independence with wavelength rule out stellar variability or a dust cloud or debris disk partially occulting the star as the source of the signal; we conclude that it must instead be planetary in origin. The existence of K2-33b suggests that close-in planets can form in situ or migrate within similar to 10 Myr, e.g., via interactions with a disk, and that long-timescale dynamical migration such as by Lidov-Kozai or planet-planet scattering is not responsible for all short-period planets.
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| 16. |
- Haaksma, Miriam L., et al.
(författare)
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The Impact of Frailty and Comorbidity on Institutionalization and Mortality in Persons With Dementia : A Prospective Cohort Study
- 2019
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 20:2, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The predictive value of frailty and comorbidity, in addition to more readily available information, is not widely studied. We determined the incremental predictive value of frailty and comorbidity for mortality and institutionalization across both short and long prediction periods in persons with dementia.Design: Longitudinal clinical cohort study with a follow-up of institutionalization and mortality occurrence across 7 years after baseline.Setting and Participants: 331 newly diagnosed dementia patients, originating from 3 Alzheimer centers (Amsterdam, Maastricht, and Nijmegen) in the Netherlands, contributed to the Clinical Course of Cognition and Comorbidity (4C) Study.Measures: We measured comorbidity burden using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and constructed a Frailty Index (FI) based on 35 items. Time-to-death and time-to-institutionalization from dementia diagnosis onward were verified through linkage to the Dutch population registry.Results: After 7 years, 131 patients were institutionalized and 160 patients had died. Compared with a previously developed prediction model for survival in dementia, our Cox regression model showed a significant improvement in model concordance (U) after the addition of baseline CIRS-G or FI when examining mortality across 3 years (FI: U = 0.178, P = .005, CIRS-G: U = 0.180, P = .012), but not for mortality across 6 years (FI: U = 0.068, P = .176, CIRS-G: U = 0.084, P = .119). In a competing risk regression model for time-to-institutionalization, baseline CIRS-G and FI did not improve the prediction across any of the periods.Conclusions: Characteristics such as frailty and comorbidity change over time and therefore their predictive value is likely maximized in the short term. These results call for a shift in our approach to prognostic modeling for chronic diseases, focusing on yearly predictions rather than a single prediction across multiple years. Our findings underline the importance of considering possible fluctuations in predictors over time by performing regular longitudinal assessments in future studies as well as in clinical practice.
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| 17. |
- Handels, Ron L. H., et al.
(författare)
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Natural Progression Model of Cognition and Physical Functioning among People with Mild Cognitive Impairment and Alzheimer's Disease
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 37:2, s. 357-365
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Tidskriftsartikel (refereegranskat)abstract
- Background: Empirical models of the natural history of Alzheimer's disease (AD) may help to evaluate new interventions for AD. Objective: We aimed to estimate AD-free survival time in people with mild cognitive impairment (MCI) and decline of cognitive and physical function in AD cases. Methods: Within the Kungsholmen project, 153 incident MCI and 323 incident AD cases (international criteria) were identified during 9 years of follow-up in a cognitively healthy cohort of elderly people aged >= 75 at baseline (n = 1,082). Global cognitive function was assessed with the Mini-Mental State Examination (MMSE), and daily life function was evaluated with the Katz index of activities of daily living (ADL) at each follow-up examination. Data were analyzed using parametric survival analysis and mixed effect models. Results: Median AD-free survival time of 153 participants with incident MCI was 3.5 years. Among 323 incident AD cases, the cognitive decline was 1.84 MMSE points per year, which was significantly associated with age. Physical functioning declined by 0.38 ADL points per year and was significantly associated with age, education, and MMSE, but not with gender. Conclusion: Elderly people with MCI may develop AD in approximately 3.5 years. Both cognitive and physical function may decline gradually after AD onset. The empirical models can be used to evaluate long-term disease progression of new interventions for AD.
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| 18. |
- Hansson, Lars, et al.
(författare)
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Annie, a Tool for Integrating Ergonomics in the Design of Car Interiors
- 1999
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- An example of a result from a long-term cooperation with Lund University (together with professor Roland Axelsson at the Department for Work Environment) there some of the authors. (Engström) gained extensive grants (Wallenberg Stifelsen regarding equipment as well as other founding from e.g. the Swedish Work Environment Found).
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| 23. |
- Matteucci, A, et al.
(författare)
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Parkin-dependent regulation of the MCU complex component MICU1
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 14199-
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Tidskriftsartikel (refereegranskat)abstract
- The mitochondrial Ca2+ uniporter machinery is a multiprotein complex composed by the Ca2+ selective pore-forming subunit, the mitochondrial uniporter (MCU), and accessory proteins, including MICU1, MICU2 and EMRE. Their concerted action is required to fine-tune the uptake of Ca2+ into the mitochondrial matrix which both sustains cell bioenergetics and regulates the apoptotic response. To adequately fulfil such requirements and avoid impairment in mitochondrial Ca2+ handling, the intracellular turnover of all the MCU components must be tightly regulated. Here we show that the MCU complex regulator MICU1, but not MCU and MICU2, is rapidly and selectively degraded by the Ubiquitin Proteasome System (UPS). Moreover, we show that the multifunctional E3 ubiquitin ligase Parkin (PARK2), whose mutations cause autosomal recessive early-onset Parkinson’s disease (PD), is a potential candidate involved in this process since its upregulation strongly decreases the basal level of MICU1. Parkin was found to interact with MICU1 and, interestingly, Parkin Ubl-domain, but not its E3-ubquitin ligase activity, is required for the degradation of MICU1, suggesting that in addition to the well documented role in the control of Parkin basal auto-inhibition, the Ubl-domain might exert important regulatory functions by acting as scaffold for the proteasome-mediated degradation of selected substrates under basal conditions, i.e. to guarantee their turnover. We have found that also MICU2 stability was affected upon Parkin overexpression, probably as a consequence of increased MICU1 degradation. Our findings support a model in which the PD-related E3 ubiquitin ligase Parkin directly participates in the selective regulation of the MCU complex regulator MICU1 and, indirectly, also of the MICU2 gatekeeper, thus indicating that Parkin loss of function could contribute to the impairment of the ability of mitochondria to handle Ca2+ and consequently to the pathogenesis of PD.
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