| 21. |
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| 22. |
- Wierenga, Lara M., et al.
(författare)
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Greater male than female variability in regional brain structure across the lifespan
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 470-499
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Tidskriftsartikel (refereegranskat)abstract
- For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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| 23. |
- Woodruff, J. B., et al.
(författare)
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Regulated assembly of a supramolecular centrosome scaffold in vitro
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 348:6236, s. 808-812
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Tidskriftsartikel (refereegranskat)abstract
- The centrosome organizes microtubule arrays within animal cells and comprises two centrioles surrounded by an amorphous protein mass called the pericentriolar material (PCM). Despite the importance of centrosomes as microtubule-organizing centers, the mechanism and regulation of PCM assembly are not well understood. In Caenorhabditis elegans, PCM assembly requires the coiled-coil protein SPD-5.We found that recombinant SPD-5 could polymerize to form micrometer-sized porous networks in vitro. Network assembly was accelerated by two conserved regulators that control PCM assembly in vivo, Polo-like kinase-1 and SPD-2/Cep192. Only the assembled SPD-5 networks, and not unassembled SPD-5 protein, functioned as a scaffold for other PCM proteins. Thus, PCM size and binding capacity emerge from the regulated polymerization of one coiled-coil protein to form a porous network.
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| 24. |
- Zimmermann, E., et al.
(författare)
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Is the adiposity-associated FTO gene variant related to all-cause mortality independent of adiposity? Meta-analysis of data from 169,551 Caucasian adults
- 2015
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Ingår i: Obesity Reviews. - : Wiley. - 1467-7881. ; 16:4, s. 327-340
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Tidskriftsartikel (refereegranskat)abstract
- Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n=169,551; 0.32kgm(-2); 95% CI 0.28-0.32, P<1x10(-32)), WC (n=152,631; 0.76cm; 0.68-0.84, P<1x10(-32)) and FMI (n=48,192; 0.17kgm(-2); 0.13-0.22, P=1.0x10(-13)). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P=0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P=0.662) and for FMI (HR: 1.00; 0.96-1.04, P=0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.
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| 25. |
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| 26. |
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| 27. |
- Hollestein, V, et al.
(författare)
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Excitatory/inhibitory imbalance in autism: the role of glutamate and GABA gene-sets in symptoms and cortical brain structure
- 2023
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 13:1, s. 18-
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Tidskriftsartikel (refereegranskat)abstract
- The excitatory/inhibitory (E/I) imbalance hypothesis posits that imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) mechanisms underlies the behavioral characteristics of autism. However, how E/I imbalance arises and how it may differ across autism symptomatology and brain regions is not well understood. We used innovative analysis methods—combining competitive gene-set analysis and gene-expression profiles in relation to cortical thickness (CT) to investigate relationships between genetic variance, brain structure and autism symptomatology of participants from the AIMS-2-TRIALS LEAP cohort (autism = 359, male/female = 258/101; neurotypical control participants = 279, male/female = 178/101) aged 6–30 years. Using competitive gene-set analyses, we investigated whether aggregated genetic variation in glutamate and GABA gene-sets could be associated with behavioral measures of autism symptoms and brain structural variation. Further, using the same gene-sets, we corelated expression profiles throughout the cortex with differences in CT between autistic and neurotypical control participants, as well as in separate sensory subgroups. The glutamate gene-set was associated with all autism symptom severity scores on the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R) within the autistic group. In adolescents and adults, brain regions with greater gene-expression of glutamate and GABA genes showed greater differences in CT between autistic and neurotypical control participants although in opposing directions. Additionally, the gene expression profiles were associated with CT profiles in separate sensory subgroups. Our results suggest complex relationships between E/I related genetics and autism symptom profiles as well as brain structure alterations, where there may be differential roles for glutamate and GABA.
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| 28. |
- Mason, L., et al.
(författare)
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Preference for biological motion is reduced in ASD : implications for clinical trials and the search for biomarkers
- 2021
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Ingår i: Molecular Autism. - : Springer Nature. - 2040-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology.Methods: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N = 282) and non-autistic control (N = 204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL).Results: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline.Limitations: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons.Conclusions: Biological motion preference elicits small-to-medium-sized case–control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear.
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| 29. |
- Baumeister, J., et al.
(författare)
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Brain Activity in Predictive Sensorimotor Control for Landings: an EEG Pilot Study
- 2013
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Ingår i: International Journal of Sports Medicine. - : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 34:12, s. 1106-1111
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Tidskriftsartikel (refereegranskat)abstract
- Landing from a jump is related to predictive sensorimotor control. Frontal, central and parietal brain areas are known to play a role in this process based on online sensory feedback. This can be measured by EEG. However, there is only limited knowledge about brain activity during predictive preparation for drop landings (DL). The purpose is to demonstrate changes in brain activity in preparation for DL in different conditions. After resting, 10 athletes performed a series of DLs and were asked to concentrate on the landing preparation for 10s before an auditory signal required them to drop land from a 30cm platform. This task was executed before and after a standardized fatigue protocol. EEG spectral power was calculated during DL preparation. Frontal Theta power was increased during preparation compared to rest. Parietal Alpha-2 power demonstrated higher values in preparation after fatigue condition while lower limb kinematics remained unchanged. Cortical activity in frontal and parietal brain areas is sensitive for predictive sensorimotor control of drop landings. Frontal Theta power demonstrates an increase and is related to higher attentional control. In a fatigued condition the parietal Alpha-2 power increase might be related to a deactivation in the somatosensory brain areas.
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| 30. |
- Moschini, M, et al.
(författare)
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Open Versus Robotic Cystectomy: A Propensity Score Matched Analysis Comparing Survival Outcomes
- 2019
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: To assess the differential effect of robotic assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) on survival outcomes in matched analyses performed on a large multicentric cohort. Methods: The study included 9757 patients with urothelial bladder cancer (BCa) treated in a consecutive manner at each of 25 institutions. All patients underwent radical cystectomy with bilateral pelvic lymphadenectomy. To adjust for potential selection bias, propensity score matching 2:1 was performed with two ORC patients matched to one RARC patient. The propensity-matched cohort included 1374 patients. Multivariable competing risk analyses accounting for death of other causes, tested association of surgical technique with recurrence and cancer specific mortality (CSM), before and after propensity score matching. Results: Overall, 767 (7.8%) patients underwent RARC and 8990 (92.2%) ORC. The median follow-up before and after propensity matching was 81 and 102 months, respectively. In the overall population, the 3-year recurrence rates and CSM were 37% vs. 26% and 34% vs. 24% for ORC vs. RARC (all p values > 0.1), respectively. On multivariable Cox regression analyses, RARC and ORC had similar recurrence and CSM rates before and after matching (all p values > 0.1). Conclusions: Patients treated with RARC and ORC have similar survival outcomes. This data is helpful in consulting patients until long term survival outcomes of level one evidence is available.
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