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| 2. |
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| 3. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 4. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 6. |
- Andela, C. D., et al.
(författare)
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MECHANISMS IN ENDOCRINOLOGY Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies
- 2015
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 173:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cushing's syndrome (CS) is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids. Objective: To review publications evaluating brain characteristics in patients with CS using magnetic resonance imaging (MRI). Methods: Systematic review of literature published in PubMed, Embase, Web of Knowledge, and Cochrane databases. Results: Nineteen studies using MRI in patients with CS were selected, including studies in patients with active disease, patients in long-term remission, and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e., cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life). Conclusion: Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.
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| 9. |
- Gregoire, V, et al.
(författare)
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Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NCRI, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines
- 2018
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Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 1879-0887. ; 126:1, s. 3-24
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Lim, Yi Huey, et al.
(författare)
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Effect of optic flow on postural control in children and adults with autism spectrum disorder
- 2018
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Ingår i: Neuroscience. - : Elsevier. - 0306-4522 .- 1873-7544. ; 393, s. 138-149
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with autism spectrum disorder (ASD) have been associated with sensorimotor difficulties, commonly presented by poor postural control. Postural control is necessary for all motor behaviors. However, findings concerning the effect of visual motion on postural control and the age progression of postural control in individuals with ASD are inconsistent. The aims of the present study were to examine postural responses to optic flow in children and adults with and without ASD, postural responses to optic flow in the central and peripheral visual fields, and the changes in postural responses between the child and adult groups. Thirty-three children (8–12 years old) and 33 adults (18–50 years old) with and without ASD were assessed on quiet standing for 60 seconds under conditions of varying optic flow illusions, consisting of different combinations of optic flow directions and visual field display. The results showed that postural responses to most optic flow conditions were comparable between children with and without ASD and between adults with and without ASD. However, adults with ASD appeared more responsive to forward-moving optic flow in the peripheral visual field compared with typically developed adults. The findings suggest that children and adults with ASD may not display maladaptive postural responses all the time. In addition, adults in the ASD group may have difficulties prioritizing visual information in the central visual field over visual information in the peripheral visual field when in unfamiliar environments, which may have implications in understanding their motor behaviors in new surroundings.
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| 12. |
- Lim, Yi Huey, et al.
(författare)
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Effect of visual information on postural control in adults with autism spectrum disorder
- 2019
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Ingår i: Journal of autism and developmental disorders. - : Springer. - 0162-3257 .- 1573-3432. ; 49:12, s. 4731-4739
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Tidskriftsartikel (refereegranskat)abstract
- Sensory processing difficulties affect the development of sensorimotor skills in individuals with autism spectrum disorder (ASD). However, the effect of sensory information on postural control is unclear in the ASD adult population. The present study examined the effect of visual information on postural control as well as the attentional demands associated with postural control in fourteen adults with ASD and seventeen typically developed adults. The results showed that postural sway and attention demands of postural control were larger in adults with ASD than in typically developed adults. These findings indicate that visual processing used for postural control may be different in adults with ASD. Further research in visual field processing and visual motion processing may elucidate these sensorimotor differences.
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| 13. |
- Lim, Yi Huey, et al.
(författare)
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Postural control adaptation to optic flow in children and adults with autism spectrum disorder
- 2019
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Ingår i: Gait & Posture. - : Elsevier. - 0966-6362 .- 1879-2219. ; 72, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sensory reweighting is important for humans to flexibly up-weigh and down-weigh sensory information in dynamic environments. There is an element of time involved in the sensory reweighting process. A longer time spent on sensory reweighting may increase the destabilizing effect of postural control. Individuals with autism spectrum disorder (ASD) are reported to have poor postural control. It is uncertain if a different sensory reweighting process underlies the postural control deficit in children and adults with ASD.Research question: To explore the sensory reweighting capability in ASD, the present study examined whether the temporal domains of postural control differed in children and adults, with and without ASD under various optic flow conditions.Methods: Thirty-three children (8–12 years old) and 33 adults (18–50 years old) with and without ASD underwent quiet standing in six radial optic flow conditions. Each condition lasted for 60 s and was shown twice to all participants. For each optic flow condition, changes in postural response within-trial and between-trials were measured.Results: Under various optic flow illusions, both children with and without ASD took a longer time to restore their posture compared with adults with and without ASD. Nonetheless, all groups demonstrated comparable abilities to adjust their posture to one that is close to the baseline position after one exposure to the optic flow stimulation.Significance: The present study showed that the temporal domains of postural control under different optic flow conditions were similar between individuals with and without ASD from the same age group. The ability to down-weigh visual information efficiently comes with the developmental progression of the sensory reweighting system. These findings suggest that the sensory reweighting process does not elucidate the postural control deficits in individuals with ASD and thus alternative explanations to determine the underlying mechanism for postural instability are needed.
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| 14. |
- Marshall, D. G., et al.
(författare)
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Morganella morganii bacteria produces phenol as the sex pheromone of the New Zealand grass grub from tyrosine in the colleterial gland
- 2016
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Ingår i: The Science of Nature. - : Springer Science and Business Media LLC. - 0028-1042 .- 1432-1904. ; 103:7-8
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Tidskriftsartikel (refereegranskat)abstract
- Costelytra zealandica (Coleoptera: Scarabeidae) is a univoltine endemic species that has colonised and become a major pest of introduced clover and ryegrass pastures that form about half of the land area of New Zealand. Female beetles were previously shown to use phenol as their sex pheromone produced by symbiotic bacteria in the accessory or colleterial gland. In this study, production of phenol was confirmed from the female beetles, while bacteria were isolated from the gland and tested for attractiveness towards grass grub males in traps in the field. The phenol-producing bacterial taxon was identified by partial sequencing of the 16SrRNA gene, as Morganella morganii. We then tested the hypothesis that the phenol sex pheromone is biosynthesized from the amino acid tyrosine by the bacteria. This was shown to be correct, by addition of isotopically labelled tyrosine (C-13) to the bacterial broth, followed by detection of the labelled phenol by SPME-GCMS. Elucidation of this pathway provides specific evidence how the phenol is produced as an insect sex pheromone by a mutualistic bacteria.
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| 15. |
- Niklasson, Mia, et al.
(författare)
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Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses
- 2017
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 77:7, s. 1741-1752
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Tidskriftsartikel (refereegranskat)abstract
- Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstreamsignaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. Our results suggest new therapeutic targets to attack aggressive gliomas.
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| 16. |
- Perley, Daniel A., et al.
(författare)
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The fast, luminous ultraviolet transient AT2018cow : extreme supernova, or disruption of a star by an intermediate-mass black hole?
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 484:1, s. 1031-1049
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Tidskriftsartikel (refereegranskat)abstract
- Wide-field optical surveys have begun to uncover large samples of fast (t(rise) less than or similar to 5 d), luminous (M-peak < 18), blue transients. While commonly attributed to the breakout of a supernova shock into a dense wind, the great distances to the transients of this class found so far have hampered detailed investigation of their properties. We present photometry and spectroscopy from a comprehensive worldwide campaign to observe AT 2018cow (ATLAS 18qqn), the first fast-luminous optical transient to be found in real time at low redshift. Our first spectra (<2 days after discovery) are entirely featureless. A very broad absorption feature suggestive of near-relativistic velocities develops between 3 and 8 days, then disappears. Broad emission features of H and He develop after >10 days. The spectrum remains extremely hot throughout its evolution, and the photospheric radius contracts with time (receding below R < 10 (14) cm after 1 month). This behaviour does not match that of any known supernova, although a relativistic jet within a fallback supernova could explain some of the observed features. Alternatively, the transient could originate from the disruption of a star by an intermediate-mass black hole, although this would require long-lasting emission of highly super-Eddington thermal radiation. In either case, AT 2018cow suggests that the population of fast luminous transients represents a new class of astrophysical event. Intensive follow-up of this event in its late phases, and of any future events found at comparable distance, will be essential to better constrain their origins.
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| 17. |
- Schmidt, Linnéa, et al.
(författare)
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Case-specific potentiation of glioblastoma drugs by pterostilbene
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:45, s. 73200-73215
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures. The potentiating effect of pterostilbene was observed to a varying degree across a panel of 41 patient-derived GCs, and correlated in a case specific manner with the presence of missense mutation of EGFR and PIK3CA and a focal deletion of the chromosomal region 1p32. We identify pterostilbene-induced cell cycle arrest, synergistic inhibition of MAPK activity and induction of Thioredoxin interacting protein (TXNIP) as possible mechanisms behind pterostilbene's effect. Our results highlight a nontoxic stilbenoid compound as a modulator of anticancer drug response, and indicate that pterostilbene might be used to modulate two anticancer compounds in well-defined sets of GBM patients.
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| 18. |
- Wee, Boyoung, et al.
(författare)
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ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Glioma cells with stem cell traits are thought to be responsible for tumor maintenance and therapeutic failure. Such cells can be enriched based on their inherent drug efflux capability mediated by the ABC transporter ABCG2 using the side population assay, and their characteristics include increased self-renewal, high stem cell marker expression and high tumorigenic capacity in vivo. Here, we show that ABCG2 can actively drive expression of stem cell markers and self-renewal in glioma cells. Stem cell markers and self-renewal was enriched in cells with high ABCG2 activity, and could be specifically inhibited by pharmacological and genetic ABCG2 inhibition. Importantly, despite regulating these key characteristics of stem-like tumor cells, ABCG2 activity did not affect radiation resistance or tumorigenicity in vivo. ABCG2 effects were Notch-independent and mediated by diverse mechanisms including the transcription factor Mef. Our data demonstrate that characteristics of tumor stem cells are separable, and highlight ABCG2 as a potential driver of glioma stemness.
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