| 11. |
- Layton, K. K. S., et al.
(författare)
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Predicting the future of our oceans : Evaluating genomic forecasting approaches in marine species
- 2024
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Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 30:3
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Forskningsöversikt (refereegranskat)abstract
- Climate change is restructuring biodiversity on multiple scales and there is a pressing need to understand the downstream ecological and genomic consequences of this change. Recent advancements in the field of eco-evolutionary genomics have sought to include evolutionary processes in forecasting species' responses to climate change (e.g., genomic offset), but to date, much of this work has focused on terrestrial species. Coastal and offshore species, and the fisheries they support, may be even more vulnerable to climate change than their terrestrial counterparts, warranting a critical appraisal of these approaches in marine systems. First, we synthesize knowledge about the genomic basis of adaptation in marine species, and then we discuss the few examples where genomic forecasting has been applied in marine systems. Next, we identify the key challenges in validating genomic offset estimates in marine species, and we advocate for the inclusion of historical sampling data and hindcasting in the validation phase. Lastly, we describe a workflow to guide marine managers in incorporating these predictions into the decision-making process. Predicting climate change impacts is of central importance in marine ecosystems that provide a major source of nutrition to global communities and this work must be based on a sound understanding of both ecological and genomic impacts. This opinion synthesizes knowledge about the genomic basis of adaptation in marine species, highlights the few examples where genomic forecasting has been applied in marine systems, identifies the key challenges in validating genomic offset estimates in marine species, and provides a workflow to guide marine managers in incorporating these predictions into the decision-making process.
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| 12. |
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| 13. |
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| 14. |
- Cristóbal, Andrés, et al.
(författare)
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Automatic Characterization of Block-In-Matrix Rock Outcrops through Segmentation Algorithms and Its Application to an Archaeo-Mining Case Study
- 2024
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Ingår i: Geosciences. - : MDPI AG. - 2076-3263. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- The mechanical behavior of block-in-matrix materials is heavily dependent on their block content. This parameter is in most cases obtained through visual analyses of the ground through digital imagery, which provides the areal block proportion (ABP) of the area analyzed. Nowadays, computer vision models have the capability to extract knowledge from the information stored in these images. In this research, we analyze and compare classical feature-detection algorithms with state-of-the-art models for the automatic calculation of the ABP parameter in images from surface and underground outcrops. The outcomes of this analysis result in the development of a framework for ABP calculation based on the Segment Anything Model (SAM), which is capable of performing this task at a human level when compared with the results of 32 experts in the field. Consequently, this model can help reduce human bias in the estimation of mechanical properties of block-in-matrix materials as well as contain underground technical problems due to mischaracterization of rock block quantities and dimensions. The methodology used to obtain the ABP at different outcrops is combined with estimates of the rock matrix properties and other characterization techniques to mechanically characterize the block-in-matrix materials. The combination of all these techniques has been applied to analyze, understand and try, for the first time, to model Roman gold-mining strategies in an archaeological site in NW Spain. This mining method is explained through a 2D finite-element method numerical model.
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| 15. |
- Estévez-Silva, Héctor M., et al.
(författare)
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Pridopidine modifies disease phenotype in a SOD1 mouse model of amyotrophic lateral sclerosis
- 2022
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Ingår i: European Journal of Neuroscience. - : John Wiley & Sons. - 0953-816X .- 1460-9568. ; 55:5, s. 1356-1372
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a lethal and incurable neurodegenerative disease due to the loss of upper and lower motor neurons, which leads to muscle weakness, atrophy, and paralysis. Sigma-1 receptor (σ-1R) is a ligand-operated protein that exhibits pro-survival and anti-apoptotic properties. In addition, mutations in its codifying gene are linked to development of juvenile ALS pointing to an important role in ALS. Here, we investigated the disease-modifying effects of pridopidine, a σ-1R agonist, using a delayed onset SOD1 G93A mouse model of ALS. Mice were administered a continuous release of pridopidine (3.0 mg/kg/day) for 4 weeks starting before the appearance of any sign of muscle weakness. Mice were monitored weekly and several behavioural tests were used to evaluate muscle strength, motor coordination and gait patterns. Pridopidine-treated SOD1 G93A mice showed genotype-specific effects with the prevention of cachexia. In addition, these effects exhibited significant improvement of motor behaviour 5 weeks after treatment ended. However, the survival of the animals was not extended. In summary, these results show that pridopidine can modify the disease phenotype of ALS-associated cachexia and motor deficits in a SOD1 G93A mouse model.
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| 16. |
- Estevez-Ventosa, Xian, et al.
(författare)
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Scale effects on triaxial peak and residual strength of granite and preliminary PFC3D models
- 2022
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Ingår i: Geomechanics and Engineering. - : TECHNO-PRESS. - 2005-307X .- 2092-6219. ; 31:5, s. 461-476
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Tidskriftsartikel (refereegranskat)abstract
- Research studies on the scale effect on triaxial strength of intact rocks are scarce, being more common those in uniaxial strength. In this paper, the authors present and briefly interpret the peak and residual strength trends on a series of triaxial tests on different size specimens (30 mm to 84 mm diameter) of an intact granitic rock at confinements ranging from 0 to 15 MPa. Peak strength tends to grow from smaller to standard-size samples (54 mm) and then diminishes for larger values at low confinement. However, a slight change in strength is observed at higher confinements. Residual strength is observed to be much less size-dependent. Additionally, this study introduces preliminary modelling approaches of these laboratory observations with the help of three-dimensional particle flow code (PFC3D) simulations based on bonded particle models (BPM). Based on previous studies, two modelling approaches have been followed. In the first one, the maximum and minimum particle diameter (Dmax and Dmin) are kept constant irrespective of the sample size, whereas in the second one, the resolution (number of particles within the sample or phi v) was kept constant. Neither of these approaches properly represent the observations in actual laboratory tests, even if both of them show some interesting capabilities reported in this document. Eventually, some suggestions are provided to proceed towards improving modelling approaches to represent observed scale effects.
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| 17. |
- González-Fernández, Manuel A., et al.
(författare)
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Size effects on strength and deformability of artificially jointed hard rock
- 2024
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Ingår i: International Journal of Rock Mechanics And Mining Sciences. - : Elsevier Ltd. - 1365-1609 .- 1873-4545. ; 176
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Tidskriftsartikel (refereegranskat)abstract
- An extensive experimental study is presented including around 140 triaxial compressive strength tests on artificially jointed hard rock. The experiments were performed on cylindrical and jointed specimens with either 1 sub-vertical and 2 sub-horizontal (1 + 2) or 2 sub-vertical and 3-sub-horizontal (2 + 3) joint sets. The specimen diameter consisted of 38, 54 and 84 mm and the rock was Blanco Mera granite. The confining pressures ranged between 0.2 and 15 MPa and such a testing program complements the previous study in this regard with about 100 triaxial tests on intact rock specimens. A complete set of stress-strain curves were obtained from the experiments followed by extracting the peak and residual strengths as well as indicative deformability parameters (elastic and Poisson's ratio). For the jointed specimens, the indirect strain measurement was corrected to implicitly calculate the elastic parameters following the energy-based concept. It was found that the peak strength is joint set dependent as per the conventional rock mass classification systems. For jointed specimens a moderate strength size effect was observed in which the peak strength tended to increase with size from 38 mm to 54 mm and then decreased with a rise in specimen diameter. Also, it was concluded that the effect of size on peak strength become less prominent in cases with more joints and the influence of additional jointing becomes less significant for larger specimens; both are novel findings which have not been explored before. The approximated variable elastic parameters of jointed specimens exhibited size independency but joint and confinement dependency, while the variable Poisson's ratios specifically, appeared to be size and joint set independent. The presented stress-strain data from granite specimens suggests that the mechanical parameters of jointed rock are largely controlled by the rock structure where the specimen size can play a significant role, particularly at low confinements.
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| 18. |
- Hill, Sandra Malmgren, 1987, et al.
(författare)
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VCP/p97 regulates Beclin-1-dependent autophagy initiation
- 2021
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Ingår i: Nature Chemical Biology. - : Springer Science and Business Media LLC. - 1552-4450 .- 1552-4469. ; 17, s. 448-455
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy is an essential cellular process that removes harmful protein species, and autophagy upregulation may be able to protect against neurodegeneration and various pathogens. Here, we have identified the essential protein VCP/p97 (VCP, valosin-containing protein) as a novel regulator of autophagosome biogenesis, where VCP regulates autophagy induction in two ways, both dependent on Beclin-1. Utilizing small-molecule inhibitors of VCP ATPase activity, we show that VCP stabilizes Beclin-1 levels by promoting the deubiquitinase activity of ataxin-3 towards Beclin-1. VCP also regulates the assembly and activity of the Beclin-1-containing phosphatidylinositol-3-kinase (PI3K) complex I, thus regulating the production of PI(3)P, a key signaling lipid responsible for the recruitment of downstream autophagy factors. A decreased level of VCP, or inhibition of its ATPase activity, impairs starvation-induced production of PI(3)P and limits downstream recruitment of WIPI2, ATG16L and LC3, thereby decreasing autophagosome formation, illustrating an important role for VCP in early autophagy initiation.
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| 19. |
- Mediavilla, Tomás, et al.
(författare)
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Learning-related contraction of gray matter in rodent sensorimotor cortex is associated with adaptive myelination.
- 2022
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Ingår i: eLife. - : eLife Sciences Publications. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- From observations in rodents, it has been suggested that the cellular basis of learning-dependent changes, detected using structural MRI, may be increased dendritic spine density, alterations in astrocyte volume, and adaptations within intracortical myelin. Myelin plasticity is crucial for neurological function, and active myelination is required for learning and memory. However, the dynamics of myelin plasticity and how it relates to morphometric-based measurements of structural plasticity remains unknown. We used a motor skill learning paradigm in male mice to evaluate experience-dependent brain plasticity by voxel-based morphometry (VBM) in longitudinal MRI, combined with a cross-sectional immunohistochemical investigation. Whole-brain VBM revealed nonlinear decreases in gray matter volume (GMV) juxtaposed to nonlinear increases in white matter volume (WMV) within GM that were best modeled by an asymptotic time course. Using an atlas-based cortical mask, we found nonlinear changes with learning in primary and secondary motor areas and in somatosensory cortex. Analysis of cross-sectional myelin immunoreactivity in forelimb somatosensory cortex confirmed an increase in myelin immunoreactivity followed by a return towards baseline levels. Further investigations using quantitative confocal microscopy confirmed these changes specifically to the length density of myelinated axons. The absence of significant histological changes in cortical thickness suggests that nonlinear morphometric changes are likely due to changes in intracortical myelin for which morphometric WMV in somatosensory cortex significantly correlated with myelin immunoreactivity. Together, these observations indicate a nonlinear increase of intracortical myelin during learning and support the hypothesis that myelin is a component of structural changes observed by VBM during learning.
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| 20. |
- Scahill, R. I., et al.
(författare)
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Biological and clinical characteristics of gene carriers far from predicted onset in the Huntington?s disease Young Adult Study (HD-YAS): a cross-sectional analysis
- 2020
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Ingår i: Lancet Neurology. - : Elsevier BV. - 1474-4422. ; 19:6, s. 502-512
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Tidskriftsartikel (refereegranskat)abstract
- Background Disease-modifying treatments are in development for Huntington's disease; crucial to their success is to identify a timepoint in a patient's life when there is a measurable biomarker of early neurodegeneration while clinical function is still intact. We aimed to identify this timepoint in a novel cohort of young adult premanifest Huntington's disease gene carriers (preHD) far from predicted clinical symptom onset. Methods We did the Huntington's disease Young Adult Study (HD-YAS) in the UK. We recruited young adults with preHD and controls matched for age, education, and sex to ensure each group had at least 60 participants with imaging data, accounting for scan fails. Controls either had a family history of Huntington's disease but a negative genetic test, or no known family history of Huntington's disease. All participants underwent detailed neuropsychiatric and cognitive assessments, including tests from the Cambridge Neuropsychological Test Automated Battery and a battery assessing emotion, motivation, impulsivity and social cognition (EMOTICOM). Imaging (done for all participants without contraindications) included volumetric MRI, diffusion imaging, and multiparametric mapping. Biofluid markers of neuronal health were examined using blood and CSF collection. We did a cross-sectional analysis using general least-squares linear models to assess group differences and associations with age and CAG length, relating to predicted years to clinical onset. Results were corrected for multiple comparisons using the false discovery rate (FDR), with FDR <0.05 deemed a significant result. Findings Data were obtained between Aug 2, 2017, and April 25, 2019. We recruited 64 young adults with preHD and 67 controls. Mean ages of participants were 29.0 years (SD 5.6) and 29.1 years (5.7) in the preHD and control groups, respectively. We noted no significant evidence of cognitive or psychiatric impairment in preHD participants 23.6 years (SD 5.8) from predicted onset (FDR 0.22-0.87 for cognitive measures, 0.31-0.91 for neuropsychiatric measures). The preHD cohort had slightly smaller putamen volumes (FDR=0.03), but this did not appear to be closely related to predicted years to onset (FDR=0.54). There were no group differences in other brain imaging measures (FDR >0.16). CSF neurofilament light protein (NfL), plasma NfL, and CSF YKL-40 were elevated in this far-from-onset preHD cohort compared with controls (FDR<0.0001, =0.01, and =0.03, respectively). CSF NfL elevations were more likely in individuals closer to expected clinical onset (FDR <0.0001). Interpretation We report normal brain function yet a rise in sensitive measures of neurodegeneration in a preHD cohort approximately 24 years from predicted clinical onset. CSF NfL appears to be a more sensitive measure than plasma NfL to monitor disease progression. This preHD cohort is one of the earliest yet studied, and our findings could be used to inform decisions about when to initiate a potential future intervention to delay or prevent further neurodegeneration while function is intact.
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