| 1. |
- Alekseenko, Zhanna, et al.
(författare)
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Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Stem cell therapies for Parkinson’s disease (PD) have entered first-in-human clinical trials using a set of technically related methods to produce mesencephalic dopamine (mDA) neurons from human pluripotent stem cells (hPSCs). Here, we outline an approach for high-yield derivation of mDA neurons that principally differs from alternative technologies by utilizing retinoic acid (RA) signaling, instead of WNT and FGF8 signaling, to specify mesencephalic fate. Unlike most morphogen signals, where precise concentration determines cell fate, it is the duration of RA exposure that is the key-parameter for mesencephalic specification. This concentration-insensitive patterning approach provides robustness and reduces the need for protocol-adjustments between hPSC-lines. RA-specified progenitors promptly differentiate into functional mDA neurons in vitro, and successfully engraft and relieve motor deficits after transplantation in a rat PD model. Our study provides a potential alternative route for cell therapy and disease modelling that due to its robustness could be particularly expedient when use of autologous- or immunologically matched cells is considered.
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| 2. |
- Bäckström, Caroline A., et al.
(författare)
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Expecting parents’ use of digital sources in preparation for parenthood in a digitalised society – a systematic review
- 2022
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Ingår i: Digital Health. - : Sage Publications. - 2055-2076. ; 8
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Forskningsöversikt (refereegranskat)abstract
- BackgroundIn today's society, people are experiencing the rapid development of digitalisation. Expecting parents may have difficulties evaluating the information online; they are not always sure which sources of information are trustworthy, and this exacerbates their feelings of anxiety. More research is needed to broaden the knowledge about how their use of digital sources may influence their health.QuestionThe focus of this study was to explore expecting parents’ use of digital sources and how this influences their health during pregnancy.MethodsA systematic review covered the thematic analysis of 39 articles.FindingsThe analysis resulted in the following theme: The digitalised society involves both opportunities and challenges, and expecting parents express a need for a variety of digital sources to improve their health, and sub-themes: Digital sources could promote parents’ health and well-being in a digitalised society; Consuming digital health information facilitates understanding, different feelings and social connections; and A variety of digital sources may facilitate parental identification and adaption to parenthood.ConclusionDifferent digital sources in our digitalised society mean access to information and opportunities to extend social connections for expecting parents. This can promote their ability to understand and adapt to parenthood, as well as to improve their health and well-being and make the parental transition. However, professional support during face-to-face consultations cannot always be exchanged to digital sources. It is important to base digital sources devoted to expecting parents and digitalisation overall on multi-sectorial collaborations and coordination between different organisations and the digital sources they provide.
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| 3. |
- Carlén, Albin, et al.
(författare)
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Energy effiency networks for small and medium sized enterprises : bosting the energy efficiency potential by joining forces
- 2016
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Ingår i: ECEEE Industry Summer Study 2016. - : European Council for an Energy Efficient Economy (ECEEE). - 9789198048292 - 9789198048285
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Konferensbidrag (refereegranskat)abstract
- Small –and medium-sized enterprises (SMEs) remain a cornerstone in individual economies. In terms of improved energy efficiency potentials, the relative potential for SMEs is larger than for energy-intensive companies. However, the level of deployment, due to various barriers such as lack of information and high transaction costs in general remains low among industrial SMEs. The most common policy activity towards industrial SMEs are energy audit policy programs. Deployment levels from the Swedish energy audit program is roughly 50 percent of the detected cost-effective energy efficiency measures, which goes in line with results from the world’s largest program, the American IAC (Industrial Assessment Center). In order to enhance deployment levels, the Swedish Energy Agency has recently started up a national energy efficiency network program for SMEs, funded by the European Regional Development Fund. The aim of this paper is to present an ex-ante evaluation of the Swedish energy efficiency networks (EENet). The paper adds value to the growing scientific literature on energy efficiency network policy evaluation in order to further enhance scientific knowledge on energy efficiency network operationalization and evaluation. Including costs for the program administration, the subsidy effectiveness varied between 1.75 and 2.03 kWh/SEK for the different analyzed scenarios. The outcome of the paper results was that the Swedish Energy Agency reduced threshold for participation in the EENet from 2 GWh/year to 1 GWh/year in annual energy use.
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| 4. |
- Carlén, Marie
(författare)
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Adult neurogenesis : from stem cell to functional neuron
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The adult mammalian central nervous system harbors a population of neural stem cells with the ability to generate neurons, astrocytes and oligodendrocytes. These pluripotent cells can be enriched in vitro, and by directing their differentiation it would be possible to generate populations of specific neural cell types to use for transplantation. Alternatively, gene therapies stimulating stem cells directly in the brain to produce more neurons of a desired type could be an attractive treatment. It has proven difficult to express genes in stem cells. We have therefore established and evaluated different gene delivery methods, both viral and nonviral, for introduction of genes into adult neural stem cells in vitro and in vivo. Using these different techniques, we show that it is possible to target gene expression to stem cells in the adult brain, and also that it is feasible to direct the differentiation of the stem cells to neurons in vitro. In the adult mammalian brain stem cells give rise to new neurons in the olfactory bulb and the hippocampus. A question has been whether neurons born in the adult integrate into the existing neuronal network of the brain. Using a transsynaptically transported virus, we have shown that adult-born neurons in both the olfactory bulb and the hippocampus do integrate into existing circuit. Moreover, markers for neuronal activity show that a high degree of the neurons born in the adult olfactory bulb participate in odor processing, showing that adult-born neurons not only integrate, they also function as they respond to relevant environmental stimuli. The finding that ongoing neuronal cell death in the substantia nigra does not alter the total number of neurons in the same area indicates that new neurons are continuously added and compensate for the cell loss. We have therefore investigated the neurogenic potential in the substantia nigra of the midbrain, the region where dopamine-producing neurons lost in Parkinson's disease reside. Two different mitotic markers were found in dopaminergic neurons of the substantia nigra, and we identified ependymal cells lining the ventricles of the midbrain as the most likely origin for the newborn neurons. The adult-born dopaminergic neurons were found to project to their appropriate target and also to integrate into the existing synaptic network. Additionally, we could show that the rate of neurogenesis is increased after a selective lesion of dopaminergic neurons. This indicates that the rate of adult neurogenesis can be altered, a finding with implications for cellular therapies of Parkinson's disease. The regulation of neurogenesis from stem cells in the adult brain is largely unknown. Notch receptor signaling has been suggested to be involved. We found several Notch receptors and ligands, as well as downstream genes, to be expressed in the stem cell niche in the adult neurogenic lateral ventricle wall. Genetic manipulations in transgenic mice have shown that inhibition of Notch signaling in ependymal cells leads to differentiation of ependymal cells into neurons. These neurons migrate and mature similarly to neurons normally born in the lateral ventricle wall. This demonstrates that Notch signaling keeps ependymal cells in a quiescent state and that ablation of this signaling pathway induces neurogenesis by ependymal cells in vivo. This further supports the finding of ependymal cells acting as neural stem cells in the adult brain.
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| 5. |
- Carlen, Marie, et al.
(författare)
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Forebrain ependymal cells are Notch-dependent and generate neuroblasts and astrocytes after stroke
- 2009
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Ingår i: Nature Neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 12:3, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Neurons are continuously generated from stem cells in discrete regions in the adult mammalian brain. We found that ependymal cells lining the lateral ventricles were quiescent and did not contribute to adult neurogenesis under normal conditions in mice but instead gave rise to neuroblasts and astrocytes in response to stroke. Ependymal cell quiescence was actively maintained by canonical Notch signaling. Inhibition of this pathway in uninjured animals allowed ependymal cells to enter the cell cycle and produce olfactory bulb neurons, whereas forced Notch signaling was sufficient to block the ependymal cell response to stroke. Ependymal cells were depleted by stroke and failed to self-renew sufficiently to maintain their own population. Thus, although ependymal cells act as primary cells in the neural lineage to produce neurons and glial cells after stroke, they do not fulfill defining criteria for stem cells under these conditions and instead serve as a reservoir that is recruited by injury.
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| 6. |
- Guyon, Nicolas, et al.
(författare)
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Adult trkB signaling in parvalbumin interneurons is essential to prefrontal network dynamics
- 2021
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Ingår i: Journal of Neuroscience. - Stockholm : Karolinska Institutet, Dept of Neuroscience. - 0270-6474. ; 41:14, s. 3120-3141
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitory interneurons expressing parvalbumin (PV) are central to cortical network dynamics, generation of c oscillations, and cognition. Dysfunction of PV interneurons disrupts cortical information processing and cognitive behavior. Brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (trkB) signaling regulates the maturation of cortical PV interneurons but is also implicated in their adult multidimensional functions. Using a novel viral strategy for cell-type-specific and spatially restricted expression of a dominant-negative trkB (trkB.DN), we show that BDNF/trkB signaling is essential to the integrity and maintenance of prefrontal PV interneurons in adult male and female mice. Reduced BDNF/trkB signaling in PV interneurons in the medial prefrontal cortex (mPFC) resulted in deficient PV inhibition and increased baseline local field potential (LFP) activity in a broad frequency band. The altered network activity was particularly pronounced during increased activation of the prefrontal network and was associated with changed dynamics of local excitatory neurons, as well as decreased modulation of the LFP, abnormalities that appeared to generalize across stimuli and brain states. In addition, our findings link reduced BDNF/trkB signaling in prefrontal PV interneurons to increased aggression. Together our investigations demonstrate that BDNF/trkB signaling in PV interneurons in the adult mPFC is essential to local network dynamics and cognitive behavior. Our data provide direct support for the suggested association between decreased trkB signaling, deficient PV inhibition, and altered prefrontal circuitry.
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| 7. |
- Guyon, Nicolas, et al.
(författare)
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Network asynchrony underlying increased broadband gamma power
- 2021
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Ingår i: The Journal of Neuroscience. - Stockholm : Karolinska Institutet, Dept of Neuroscience. - 0270-6474. ; 41:13, s. 2944-2963
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Tidskriftsartikel (refereegranskat)abstract
- Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies expression of cortical γ rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband γ power in the local field potential. Increased baseline broadband γ is also a prominent characteristic in schizophrenia and a hallmark of network alterations induced by NMDAR antagonists, such as ketamine. Whether enhanced broadband γ is a true rhythm, and if so, whether rhythmic PV inhibition is involved or not, is debated. Asynchronous and increased firing activities are thought to contribute to broadband power increases spanning the γ band. Using male and female mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that neuronal activity with decreased synchronicity is associated with increased prefrontal broadband γ power. Specifically, reduced spike time precision and spectral leakage of spiking activity because of higher firing rates (spike “contamination”) affect the broadband γ band. Desynchronization was evident at multiple time scales, with reduced spike entrainment to the local field potential, reduced cross-frequency coupling, and fragmentation of brain states. Local application of S(1)-ketamine in (control) mice with intact NMDAR activity in PV neurons triggered network desynchronization and enhanced broadband γ power. However, our investigations suggest that disparate mechanisms underlie increased broadband γ power caused by genetic alteration of PV interneurons and ketamine-induced power increases in broadband c. Our study confirms that enhanced broadband γ power can arise from asynchronous activities and demonstrates that long-term deficiency of PV inhibition can be a contributor.
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| 8. |
- Lundh Snis, Ulrika, 1970-, et al.
(författare)
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Enhancing Quality through Work Integrated Learning and Collaboration Partnership
- 2022
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Ingår i: International Conference on Work Integrated Learning. - Trollhättan : University West. - 9789189325302 ; , s. 90-91
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- For Sweden to be able to compete in the global economy, our students with a degree from higher education must be ready for a career in working life. Today's work life is facing a major ongoing transformation, characterized by increased complexity, higher specialization, and digitalization. This demands competencies beyond traditional theoretical knowledge, such as preparing for uncertainty and unknown outcomes (Barnett, 2000; Vallo Hult & Byström, 2021). Therefore, it is essential to engage students in learning to learn, i.e., lifelong learning so that the tools and methods for learning in higher education can also be developed through future work (Billett, 2014; Islind, Norström, Vallo Hult, & Ramadani Olsson, 2021). For University West, this means that our education programs must be developed in collaboration with industry partners from the surrounding society to provide arelevant and attractive education, which corresponds to the labour market's long-term competence needs. We want our students to develop abilities and skills that enable them to be part of and drive sustainable societal development in practice.Work Integrated Learning (WIL) is University West's overarching profile, based on the concept of advanced knowledge – characterized by complex problem solving – and the mutual acknowledgment of advanced knowledge within the academy and among its partners. What characterizes WIL at University West is that we have developed and refined a combination of different approaches over a long period, including research -based WIL, through fundamental learning concepts such as socio- cultural, critical and action-oriented learning theories. These influences have shaped WIL at University West into a dynamic and academic area of knowledge and subject. In order to achieve a strategic and qualitative development of work-integrated learning, the University West Board decided to WIL-certify all educational programs with a clear sustainability perspective. The quality processis called the WIL certification process. It has now been developed at the university fortwo years.Experience andrefinements are ready to mature into an overall quality framework worth conceptualizing and disseminating to more universities that systematically want to develop WIL as an explicit quality dimension in higher educa tion. The project is still ongoing but have generated some preliminary findings and outcomes from the initial phase. Data collection activities include workshops and focus groups with selected participants from the target groups at the university (managers/prefects and teachers) as well as at the collaborative partner organization (managers and supervisors/mentors). The focus of the workshops was placed on capturing the participants understanding and perspectives on WIL as a concept, and to map the conditions for and experiences of conducting WIL in teaching and learning at work. We aim for identifying good (or less good) examples of WIL, what they are, how they are understood and why they are (or are not) important.The purpose of this paper is to describe the lessons learned so far and present a conceptual quality framework for WIL in higher education with a clear connection to sustainable development. The quality framework may function as a mediating “support object” between higher education institutions, industry partners, and actors in the surrounding society to promote WIL concepts and experiences in collaboration strategies.
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| 9. |
- Lundh Snis, Ulrika, 1970-, et al.
(författare)
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Enhancing Work-Integrated Learning (Wil) through Strategic Stakeholder Collaboration
- 2023
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Ingår i: ICERI 2023 Proceedings. - : The International Academy of Technology, Education and Development. - 9788409559428 ; , s. 1298-1302
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- For graduates to be able to compete in the global world, study programmes must include knowledge, competences and skills that ensures that students with a higher education degree are ready for both a complex working life and continuous competence development. This demands competencies beyond traditional theoretical knowledge, such as preparing for uncertainty and unknown outcomes. Therefore, it is essential to engage students in learning to learn, i.e., lifelong learning so that the tools and methods for learning in higher education can also be developed through future work.At University West (UW) in Sweden, this means that programmes are developed in collaboration with societal partners to provide a relevant and attractive educational offer. The University West uses the concept of work-integrated learning (WIL) to embrace a sustained/systematic collaboration with strategic partners outside academia. We consider that knowledge is created in the encounter between academia and our strategic partners, through the integration of knowledge, skills and competences acquired both within academia and work life.To achieve a strategic and qualitative development of work-integrated learning (WIL), the Board of University West in 2018 decided to WIL-certify all educational programs including a sustainability perspective and enhance this process by engaging in strategic partnerships with stakeholders from civic society to international companies. The process is a development of existing and future programmes and their pedagogical approach. The WIL certification process has developed into a renewal of the pedagogical approach through a development process based on a lively exchange of experiences from study programme representatives from political science to nursing; and discussions with our strategic partners that benefits both students, staff as well as the strategic partners through competence development and lifelong learning.The purpose of this paper is to describe the lessons learned so far and present a conceptual quality framework for WIL in higher education with a clear connection to sustainable development. Based on the experiences from the development of the institutional WIL project and a Swedish Innovation agency (VINNOVA) research project we aim for a better understanding and insights into how theoretical and practical knowledge can enhance learning both within academia and within strategic partners. Data collection activities include workshops and focus groups with selected participants from the target groups at the university (managers/prefects and teachers) as well as at the collaborative partner organization (managers and supervisors/mentors). Initial findings suggest that the meeting between academia, working life and the surrounding society can ensure that insights, solutions and mutual development are created to meet the challenges society faces. The paper will discuss the methodology of creating work-integrated learning environments that include well-functioning communication and a community of practice (Wenger, 1998) connecting learners, teachers, and other staff with local, regional and national stakeholders.
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| 10. |
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