| 1. |
- Wigerius, Michael, et al.
(författare)
-
Scribble controls NGF-mediated neurite outgrowth in PC12 cells
- 2013
-
Ingår i: European Journal of Cell Biology. - : Urban & Fischer. - 0171-9335 .- 1618-1298. ; 92:6-7, s. 213-221
-
Tidskriftsartikel (refereegranskat)abstract
- Neurite outgrowth is mediated by dynamic changes of the cytoskeleton and is largely controlled by Rho GTPases and their regulators. Here, we show that the polarity protein Scribble controls PC12 cell neurite outgrowth in response to nerve growth factor. Scribble knockdown decreases neurite numbers and increases neurite length. This effect is linked to TrkA the cognate receptor for NGF as pharmacological inhibition of phosphorylated TrkA (pTrkA) reduces Scribble expression. Moreover, Scribble forms a complex with the MAPK components ERK1/2 in a growth factor dependent manner. In RNAi experiments where Scribble expression is efficiently depleted sustained ERK1/2 phosphorylation is reduced. Conversely, siRNA with intermediate Scribble silencing efficiency fails to match this effect indicating that ERK1/2 activation depends on basic Scribble protein levels. Finally, Scribble translocates to the plasma membrane in response to growth factor where it complexes with HRas and Rac1 suggesting that the phenotype activated by loss of Scribble may be a result of altered GTPase activity. Together, these results demonstrate a novel role for Scribble in neurite outgrowth of PC12 cells. (c) 2013 Elsevier GmbH. All rights reserved.
|
|
| 2. |
- Wigerius, Michael, et al.
(författare)
-
Rac1 and Scribble are targets for the arrest of neurite outgrowth by TBE virus NS5
- 2010
-
Ingår i: Molecular and Cellular Neuroscience. - : Elsevier BV. - 1044-7431 .- 1095-9327. ; 44:3, s. 260-271
-
Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis virus (TBEV) causes extensive CNS disease in humans known as TBE, however, relatively little is known of the molecular mechanisms for its progress. Here, we now show that TBEV produces defects in neuronal development of PC12 cells through a function of the viral NS5 protein. The methyltransferase domain of NS5 is critical and sufficient for restriction of nerve growth factor induced neurite outgrowth. This effect is reversed by expression of NS5 mutants unable to bind Scribble and unexpectedly, in Scribble depleted cells with binding-competent NS5. Furthermore, we also demonstrate that the Rho GTPase Rac1 and the guanine nucleotide-exchange factor, βPIX are outcompeted by NS5 for binding to Scribble, linking to effects on neurite outgrowth by TBEV. Together, these findings provide the first experimental evidence that Rac1 and βPIX are indirect targets of NS5 acting through the multifunctional polarity protein Scribble to oppose neuronal differentiation. In conclusion, our results offer a potential mechanism by which TBEV alters neuronal circuitry and opens new avenues for therapeutic interventions.
|
|
| 3. |
- Stenning, Anna, et al.
(författare)
-
Neurodiversity studies : mapping out possibilities of a new critical paradigm
- 2021
-
Ingår i: Disability & Society. - : Routledge. - 0968-7599 .- 1360-0508. ; 36:9, s. 1532-1537
-
Tidskriftsartikel (refereegranskat)abstract
- Neurodevelopmental classifications and the collective idea of neurodivergence can be seen as a ‘moving target’. In our understanding, this means that it responds to the needs of society as well as potentially infinite neurological differences between humans. Therefore, rather than assume that neurodiversity exists according to the existing clinical categories of autism and related conditions (that are often centred around autism as the exemplary kind of neurodivergence), we leave the possibility open that there are other forms of difference that have yet to be defined. In the paper we explore how neurodiversity has been described as a collective property of brains, as we try to negotiate between us what it is to be human and how we can work together to ensure our flourishing and to alleviate suffering. We consider implications of this understanding of neurodiversity for autism research, and propose that we unpick the analogy between neurodiversity and biodiversity.
|
|
| 4. |
- Gustafsson Sendén, Marie, et al.
(författare)
-
Gender bias in assessment of future work ability among pain patients - an experimental vignette study of medical students' assessment
- 2019
-
Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 19:2, s. 407-414
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Pain is a prevalent problem in many countries. Women are more often on sick-leave for pain than men. Such gender differences have been explained through biological factors, different demands for on the job market, and home conditions. Fewer studies have focused on how gender stereotypes may bias the medical assessment of pain patients. The aim of the present research was to investigate if a gender bias in medical students' evaluations of chronic pain patients can contribute to explaining the gender differences in sick-leave due to pain. Specifically, we investigated whether medical students' estimates of a patient's accuracy of their own work ability and amount of domestic work differed between female and male patients, and how such estimates influenced the medical students' judgments of the patient's work ability. Methods: Medical students (n = 137; 60 women; 74 men; three unspecified) read a vignette describing a patient with pain and filled out a questionnaire. The vignette was identical and gender neutral, except for the name of the patient signaling gender. A between-subjects experimental design was used in which participants were randomly assigned to an experimental condition. Participants then judged the patient's work ability, the accuracy of the patient's self-assessed work ability, and the amount of domestic work they believed was performed by the patient. All ratings were made on seven-point items. Results: The results showed that there was no main effect of gender on perceived future work ability of the patient, F (1,131) = 0.867, p = 0.353. However, male patients were considered to be more accurate in their self-assessed work ability than female patients F (1,131) = 5.925 p = 0.016 (M-female = 4.87, SDfemale = 1.22, and M-male = 5.33, SDmale = 1.02). Moreover, female patients were thought to perform more domestic work, F (1,131) = 25.56, p < 0.001 (M-female = 4.14, SDfemale = 1.41, and M-male = 3.07, SDmale = 1.16). Finally, perceived amount of domestic work moderated the effects of perceived future work ability for female but not for male patients, B = 0.42, p = 0.005. Hence, there was a positive effect of amount of domestic work performed on work ability judgments for women, such that the more domestic work they were assumed to perform, the more they were perceived to be able to work. Conclusions: Gender stereotypes influenced assessments of future work ability in pain patients, mainly because women were assumed to perform more domestic work which had a positive effect on perceived work ability. Because domestic work should have a negative effect on recovery, expectations from the physician that domestic work is expected by female patients may in fact have the opposite effect prolonging sick-leave. Moreover, the students trusted the male patients' ability to assess their own work capacity more than women's.
|
|
| 5. |
- Jeong, D. Y., et al.
(författare)
-
Empirical assessment of biases in cerebrospinal fluid biomarkers of alzheimer’s disease : An umbrella review and re-analysis of data from meta-analyses
- 2021
-
Ingår i: European Review for Medical and Pharmacological Sciences. - : Verduci Publisher. - 1128-3602. ; 25:3, s. 1536-1547
-
Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: Alzheimer’s disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger’s test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.
|
|
| 6. |
- Tikka, Pia, et al.
(författare)
-
From naturalistic neuroscience to modeling radical embodiment with narrative enactive systems
- 2014
-
Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 8, s. 794-
-
Tidskriftsartikel (refereegranskat)abstract
- Mainstream cognitive neuroscience has begun to accept the idea of embodied mind, which assumes that the human mind is fundamentally constituted by the dynamical interactions of the brain, body, and the environment. In today’s paradigm of naturalistic neurosciences, subjects are exposed to rich contexts, such as video sequences or entire films, under relatively controlled conditions, against which researchers can interpret changes in neural responses within a time window. However, from the point of view of radical embodied cognitive neuroscience, the increasing complexity alone will not suffice as the explanatory apparatus for dynamical embodiment and situatedness of the mind. We suggest that narrative enactive systems with dynamically adaptive content as stimuli,may serve better to account for the embodied mind engaged with the surrounding world. Among the ensuing challenges for neuroimaging studies is how to interpret brain data against broad temporal contexts of previous experiences that condition the unfolding experience of nowness. We propose means to tackle this issue, as well as ways to limit the exponentially growing combinatoria of narrative paths to a controllable number.
|
|
| 7. |
- Yoon, Sojung, et al.
(författare)
-
Differential expression of MicroRNAs in Alzheimer’s disease : a systematic review and meta-analysis
- 2022
-
Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 27, s. 2405-2413
-
Forskningsöversikt (refereegranskat)abstract
- Alzheimer’s disease (AD) results in progressive cognitive decline owing to the accumulation of amyloid plaques and hyperphosphorylated tau. MicroRNAs (miRNAs) have attracted attention as a putative diagnostic and therapeutic target for neurodegenerative diseases. However, existing meta-analyses on AD and its association with miRNAs have produced inconsistent results. The primary objective of this study is to evaluate the magnitude and consistency of differences in miRNA levels between AD patients, mild cognitive impairment (MCI) patients and healthy controls (HC). Articles investigating miRNA levels in blood, brain tissue, or cerebrospinal fluid (CSF) of AD and MCI patients versus HC were systematically searched in PubMed/Medline from inception to February 16th, 2021. Fixed- and random-effects meta-analyses were complemented with the I2 statistic to measure the heterogeneity, assessment of publication bias, sensitivity subgroup analyses (AD severity, brain region, post-mortem versus ante-mortem specimen for CSF and type of analysis used to quantify miRNA) and functional enrichment pathway analysis. Of the 1512 miRNAs included in 61 articles, 425 meta-analyses were performed on 334 miRNAs. Fifty-six miRNAs were significantly upregulated (n = 40) or downregulated (n = 16) in AD versus HC and all five miRNAs were significantly upregulated in MCI versus HC. Functional enrichment analysis confirmed that pathways related to apoptosis, immune response and inflammation were statistically enriched with upregulated pathways in participants with AD relative to HC. This study confirms that miRNAs’ expression is altered in AD and MCI compared to HC. These findings open new diagnostic and therapeutic perspectives for this disorder.
|
|
| 8. |
- Lecusay, Robert, 1974-, et al.
(författare)
-
Cultural-historical activity theory and the zone of proximal development in the study of idioculture design and implementation
- 2008
-
Ingår i: Cognitive Systems Research. - : Elsevier. - 2214-4366 .- 1389-0417. ; 9:1-2, s. 92-103
-
Tidskriftsartikel (refereegranskat)abstract
- For a large part of its history cognitive science has been grounded in views of the mind based on the traditional Cartesian dualisms. These dichotomies have been reinforced in particular by the view of the mind as an encased symbol-processing system ''protected from the external world'' (Newell, A., Rosenbloom, P. S., & Laird J. E. (1990). Symbolic architectures for cognition. In M. I. Posner (Ed.), Foundations of cognitive science, Cambridge, MA: Bradford Books/MIT Press, pp. 93-131: 107). Cultural-Historical Activity Theory (CHAT) seeks to supersede Cartesianism, thinking about cognition and culture as mutually constitutive of each other. This approach analyzes thought processes as embedded in and manifested through systems of historically developing, culturally mediated activity. Consequently for CHAT, a basic unit for the study of human thought is joint mediated activity. In this paper we will discuss an example of research that follows the CHAT approach to the analysis of learning and development. The data sample is taken from a session of the Fifth Dimension, an after-school activity designed to implement CHAT principles in order to promote the cognitive and social development of adult and child participants alike. (C) 2007 Elsevier B.V. All rights reserved.
|
|
| 9. |
|
|
| 10. |
- Tikka, Pia, et al.
(författare)
-
Phenomenological Considerations on Time Consciousness under Neurocinematic Search Light
- 2014
-
Ingår i: Cinéma & cie : international film studies journal. - 2036-461X. ; XIV:22-23
-
Tidskriftsartikel (refereegranskat)abstract
- Film narratives are intrinsically time-dependent designs. This article proposes a model of narrative nowness, based on Husserl's concepts of retention and protention on one hand, and Francisco Varela's neurophenomenological exploration of time consciousness on the other, relating this further to narrative experience and its neural epiphenomena. Only recently has brain research been equipped with the possibility of dealing with temporal frames relevant for time consciousness in the scope of whole narratives. The study of cinema using neuroscientific methods and insights is referred to as neurocinematics. We promote neurocinematics as a complementary method of traditional film research, rather than an approach of brain sciences in general. Neurocinematic methods may provide film studies with new tools for re-evaluating established filmmaking conventions and developing new ways to study, for instance, the film viewer's experience and related aspects of time consciousness.
|
|
