| 1. |
- Pritchard-Jones, K, et al.
(författare)
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The state of research into children with cancer across Europe : new policies for a new decade
- 2011
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Ingår i: ecancermedicalscience. - : Ecancer Global Foundation. - 1754-6605. ; 5, s. 210-
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Tidskriftsartikel (refereegranskat)abstract
- Overcoming childhood cancers is critically dependent on the state of research. Understanding how, with whom and what the research community is doing with childhood cancers is essential for ensuring the evidence-based policies at national and European level to support children, their families and researchers. As part of the European Union funded EUROCANCERCOMS project to study and integrate cancer communications across Europe, we have carried out new research into the state of research in childhood cancers. We are very grateful for all the support we have received from colleagues in the European paediatric oncology community, and in particular from Edel Fitzgerald and Samira Essiaf from the SIOP Europe office. This report and the evidence-based policies that arise from it come at a important junction for Europe and its Member States. They provide a timely reminder that research into childhood cancers is critical and needs sustainable long-term support.
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| 2. |
- Montanier, Cedric, et al.
(författare)
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The Active Site of a Carbohydrate Esterase Displays Divergent Catalytic and Noncatalytic Binding Functions
- 2009
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885. ; 7:3, s. 687-697
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Tidskriftsartikel (refereegranskat)abstract
- Multifunctional proteins, which play a critical role in many biological processes, have typically evolved through the recruitment of different domains that have the required functional diversity. Thus the different activities displayed by these proteins are mediated by spatially distinct domains, consistent with the specific chemical requirements of each activity. Indeed, current evolutionary theory argues that the colocalization of diverse activities within an enzyme is likely to be a rare event, because it would compromise the existing activity of the protein. In contrast to this view, a potential example of multifunctional recruitment into a single protein domain is provided by CtCel5C-CE2, which contains an N-terminal module that displays cellulase activity and a C-terminal module, CtCE2, which exhibits a noncatalytic cellulose-binding function but also shares sequence identity with the CE2 family of esterases. Here we show that, unlike other CE2 members, the CtCE2 domain displays divergent catalytic esterase and noncatalytic carbohydrate binding functions. Intriguingly, these diverse activities are housed within the same site on the protein. Thus, a critical component of the active site of CtCE2, the catalytic Ser-His dyad, in harness with inserted aromatic residues, confers noncatalytic binding to cellulose whilst the active site of the domain retains its esterase activity. CtCE2 catalyses deacetylation of noncellulosic plant structural polysaccharides to deprotect these substrates for attack by other enzymes. Yet it also acts as a cellulose-binding domain, which promotes the activity of the appended cellulase on recalcitrant substrates. The CE2 family encapsulates the requirement for multiple activities by biocatalysts that attack challenging macromolecular substrates, including the grafting of a second, powerful and discrete noncatalytic binding functionality into the active site of an enzyme. This article provides a rare example of "gene sharing,'' where the introduction of a second functionality into the active site of an enzyme does not compromise the original activity of the biocatalyst.
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| 3. |
- Bergersen, L H, et al.
(författare)
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Immunogold detection of L-glutamate and D-serine in small synaptic-like microvesicles in adult hippocampal astrocytes.
- 2012
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Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 22:7, s. 1690-1697
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Tidskriftsartikel (refereegranskat)abstract
- Glutamate and the N-methyl-D-aspartate receptor ligand D-serine are putative gliotransmitters. Here, we show by immunogold cytochemistry of the adult hippocampus that glutamate and D-serine accumulate in synaptic-like microvesicles (SLMVs) in the perisynaptic processes of astrocytes. The estimated concentration of fixed glutamate in the astrocytic SLMVs is comparable to that in synaptic vesicles of excitatory nerve terminals (≈ 45 and ≈ 55 mM, respectively), whereas the D-serine level is about 6 mM. The vesicles are organized in small spaced clusters located near the astrocytic plasma membrane. Endoplasmic reticulum is regularly found in close vicinity to SLMVs, suggesting that astrocytes contain functional nanodomains, where a local Ca(2+) increase can trigger release of glutamate and/or D-serine.
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| 6. |
- Ahmadi, Khazar, et al.
(författare)
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Triple visual hemifield maps in a case of optic chiasm hypoplasia
- 2020
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119. ; 215
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Tidskriftsartikel (refereegranskat)abstract
- In humans, each hemisphere comprises an overlay of two visuotopic maps of the contralateral visual field, one from each eye. Is the capacity of the visual cortex limited to these two maps or are plastic mechanisms available to host more maps? We determined the cortical organization of the visual field maps in a rare individual with chiasma hypoplasia, where visual cortex plasticity is challenged to accommodate three hemifield maps. Using high-resolution fMRI at 7T and diffusion-weighted MRI at 3T, we found three hemiretinal inputs, instead of the normal two, to converge onto the left hemisphere. fMRI-based population receptive field mapping of the left V1–V3 at 3T revealed three superimposed hemifield representations in the left visual cortex, i.e. two representations of opposing visual hemifields from the left eye and one right hemifield representation from the right eye. We conclude that developmental plasticity including the re-wiring of local intra- and cortico-cortical connections is pivotal to support the coexistence and functioning of three hemifield maps within one hemisphere.
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| 10. |
- Morland, Cecilie, et al.
(författare)
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Vesicular uptake and exocytosis of L-aspartate is independent of sialin.
- 2013
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Ingår i: The FASEB Journal. - : Federation of American Societies for Experimental Biology. - 0892-6638 .- 1530-6860. ; 27:3, s. 1264-1274
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism of release and the role of l-aspartate as a central neurotransmitter are controversial. A vesicular release mechanism for l-aspartate has been difficult to prove, as no vesicular l-aspartate transporter was identified until it was found that sialin could transport l-aspartate and l-glutamate when reconstituted into liposomes. We sought to clarify the release mechanism of l-aspartate and the role of sialin in this process by combining l-aspartate uptake studies in isolated synaptic vesicles with immunocyotchemical investigations of hippocampal slices. We found that radiolabeled l-aspartate was taken up into synaptic vesicles. The vesicular l-aspartate uptake, relative to the l-glutamate uptake, was twice as high in the hippocampus as in the whole brain, the striatum, and the entorhinal and frontal cortices and was not inhibited by l-glutamate. We further show that sialin is not essential for exocytosis of l-aspartate, as there was no difference in ATP-dependent l-aspartate uptake in synaptic vesicles from sialin-knockout and wild-type mice. In addition, expression of sialin in PC12 cells did not result in significant vesicle uptake of l-aspartate, and depolarization-induced depletion of l-aspartate from hippocampal nerve terminals was similar in hippocampal slices from sialin-knockout and wild-type mice. Further, there was no evidence for nonvesicular release of l-aspartate via volume-regulated anion channels or plasma membrane excitatory amino acid transporters. This suggests that l-aspartate is exocytotically released from nerve terminals after vesicular accumulation by a transporter other than sialin.
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| 11. |
- Taule, T., et al.
(författare)
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Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS) in Norway: Protocol for validation and a prospective cohort study
- 2019
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Ingår i: Contemporary Clinical Trials Communications. - : Elsevier BV. - 2451-8654. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- In amyotrophic lateral sclerosis (ALS) cognitive impairment may occur. This could detrimentally influence communication between patient and health-care professionals and make clinical assessment difficult. Given the short life expectancy after diagnosis, it is crucial to accurately identify ALS patients early. Although suitable cognitive screening tools for patients with ALS are available, they have not been evaluated in a Norwegian population. Interpretation of scores for available tests and practical application of scoring is also not well established. The protocol described here involves two related studies that aim to improve the quality of ALS clinical testing instruments used in the Norwegian population. The first is a validation study that evaluates the psychometric properties of the ECAS-Norwegian. The second is a prospective cohort study that evaluates the ECAS-Norwegian as a tool to predict early changes in ability to work, drive a car and the need for advanced therapy. Study 1 is a multicenter study using international quality criteria. Patients with ALS, healthy control subjects, and control subjects with dementia will be included. Primary outcome is ECAS-Norwegian scores. In study 2, patients with ALS will be included. ECAS-Norwegian compared to Clinical Dementia Rating score and Montreal Cognitive Assessment scores will be used as a prognostic tool for working, driving, and initiating advanced life-prolonging therapy. Before clinical implementation, the ECAS-Norwegian needs to be evaluated and validated. Successful validation and implementation of the ECAS-Norwegian may provide early identification of cognitive impairment in ALS, leading to more proactive, individualized treatment.
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| 12. |
- Taule, T., et al.
(författare)
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Translation, cultural adaptation, and validation of a screening test for cognitive and behavioural changes in amyotrophic lateral sclerosis
- 2022
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Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 44:23, s. 7069-7077
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To describe challenges of translating and culturally adapting the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen into Norwegian (ECAS-N), evaluate its content validity; provide age- and education-balanced norms for verbal fluency and cut-off values for abnormal performance. Materials and methods Translation to Norwegian and back-translation to English complied with standard methods. Patients and ALS experts evaluated the relevance, comprehensiveness and comprehensibility of the translated ECAS (ECAS-N). Content validity indexes at the item level (I-CVI), scale level (S-CVI) and inter-rater agreement were calculated. Performance of controls determined norms for written and spoken verbal fluency (n = 559) and cut-off scores for abnormal performance (n = 85). Results High levels of content validity was achieved for all items of the ECAS-N, I-CVI, S-CVI and inter-rater agreement was 87.5%. Age- and education-balanced norms for written and spoken verbal fluency were produced. Cut-off scores of abnormal performance were slightly lower than the original ECAS. Conclusions The ECAS-N holds promise for detecting cognitive and behavioural impairment in Norwegian patients with ALS. Cut-off scores are situational and could slightly vary between different cultures. The ECAS-N can be used in international research, but researchers should be aware of the differences between the tests applied in the studies.
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