Stockholm, Sweden

Karolinska Institutet
Stockholm, Sweden

Karolinska Institutet is a medical university in Solna within the Stockholm urban area, Sweden, and one of Europe's largest and most prestigious medical universities. It was founded in 1810 on Kungsholmen on the west side of Stockholm; the main campus was relocated decades later to Solna, just outside Stockholm. A second campus was established more recently in Flemingsberg, Huddinge, south of Stockholm.Karolinska Institute is Sweden's third oldest medical school, after Uppsala University and Lund University . Research at Karolinska Institute accounts for more than 40% of all academic medical research in Sweden. Karolinska Institute consistently ranks among the top universities in the world on a number of prestigious ranking tables, and is currently the eighth best medical university in the world. According to the 2012 Times Higher Education World University Rankings, Karolinska Institute is ranked 32nd worldwide, 5th in Europe behind Oxford university, Cambridge university and UCL, 1st in the Nordic region and according to the 2011 Academic Ranking of World Universities, Karolinska Institute is ranked 11th in the world in the field of clinical medicine and pharmacology, 18th in life science and 3rd in pharmacy.The Karolinska University Hospital, located in Solna and Huddinge, is associated with the university as a research and teaching hospital. Together they form an academic health science centre. It is one of Sweden's largest centres for training and research, accounting for 30 percent of the medical training and 40 percent of the medical academic research conducted nationwide. While most of the medical programs are taught in Swedish, the bulk of the Ph.D. projects are conducted in English.A committee of the institute appoints the laureates for the Nobel prize in Physiology or Medicine. The Nobel Assembly at Karolinska Institutet is a body at Karolinska Institutet that awards the Nobel Prize in Physiology or Medicine. The Nobel Assembly consists of fifty professors from various medical disciplines at the Karolinska Institute. Wikipedia.

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Klingberg T.,Karolinska Institutet
Nature Reviews Neuroscience | Year: 2016

Working memory-the ability to maintain and manipulate information over a period of seconds-is a core component of higher cognitive functions. The storage capacity of working memory is limited but can be expanded by training, and evidence of the neural mechanisms underlying this effect is accumulating. Human imaging studies and neurophysiological recordings in non-human primates, together with computational modelling studies, reveal that training increases the activity of prefrontal neurons and the strength of connectivity in the prefrontal cortex and between the prefrontal and parietal cortex. Dopaminergic transmission could have a facilitatory role. These changes more generally inform us of the plasticity of higher cognitive functions. © 2016 Macmillan Publishers Limited.

Kristensson K.,Karolinska Institutet
Nature Reviews Neuroscience | Year: 2011

The nervous system is protected by barriers that restrict the invasion of pathogens. Nevertheless, mechanisms have evolved by which microbes can pass these barriers, enter and exit neurons and target various regions of the nervous system. In the brain, immune responses to pathogens are generally not robust, so microbes can hide and survive or, conversely, cause severe uncontrolled infections. Depending on their sites of entry and the regions that they target, microbes can cause diverse nervous system dysfunctions and even influence host behaviour to their own advantage. This Review discusses routes by which microbes can reach the nervous system and cause persistent or life-threatening infections. © 2011 Macmillan Publishers Limited. All rights reserved.

Chagin A.S.,Karolinska Institutet
Current Opinion in Pharmacology | Year: 2016

Although some modulators of autophagy are emerging as drugs or supplements for anti-cancer therapy, the effects of these compounds on normal tissues must be examined carefully. Here, I review the role of autophagy in skeletal tissues in this context. First, I briefly review preclinical studies indicating the role of autophagy in cancer, as well as related on-going clinical trials. Thereafter, the role of autophagy in the physiology of skeletal tissues is discussed, with a focus on recent genetic preclinical studies. Specifically, I discuss the mTOR-autophagy pathway in relationship to epiphyseal chondrocytes, articular chondrocytes, osteoblasts, osteocytes and osteoclasts and potential side effects of targeting either mTOR pathway or autophagy in general in connection with anti-cancer therapy. Current preclinical findings indicate that inhibiting autophagy will not seriously reduce bone mass and enhance osteoporosis. However, inhibition of autophagy might damage articular cartilage and cause osteoarthritis, whereas treatment with rapalogs might result in relatively beneficial effects on articular cartilage. Modulation of the mTOR pathway or autophagy during childhood may have an undesirable influence on adult height, as well as acquisition of bone mass. © 2015 Elsevier Ltd. All rights reserved.

Andersson E.R.,Karolinska Institutet | Lendahl U.,Karolinska Institutet
Nature Reviews Drug Discovery | Year: 2014

The Notch signalling pathway is evolutionarily conserved and is crucial for the development and homeostasis of most tissues. Deregulated Notch signalling leads to various diseases, such as T cell leukaemia, Alagille syndrome and a stroke and dementia syndrome known as CADASIL, and so strategies to therapeutically modulate Notch signalling are of interest. Clinical trials of Notch pathway inhibitors in patients with solid tumours have been reported, and several approaches are under preclinical evaluation. In this Review, we focus on aspects of the pathway that are amenable to therapeutic intervention, diseases that could be targeted and the various Notch pathway modulation strategies that are currently being explored.

Kiehn O.,Karolinska Institutet
Nature Reviews Neuroscience | Year: 2016

Unravelling the functional operation of neuronal networks and linking cellular activity to specific behavioural outcomes are among the biggest challenges in neuroscience. In this broad field of research, substantial progress has been made in studies of the spinal networks that control locomotion. Through united efforts using electrophysiological and molecular genetic network approaches and behavioural studies in phylogenetically diverse experimental models, the organization of locomotor networks has begun to be decoded. The emergent themes from this research are that the locomotor networks have a modular organization with distinct transmitter and molecular codes and that their organization is reconfigured with changes to the speed of locomotion or changes in gait. © 2016 Macmillan Publishers Limited. All rights reserved.

El Manira A.,Karolinska Institutet
Current Opinion in Neurobiology | Year: 2014

Spinal circuits generate coordinated locomotor movements. These hardwired circuits are supplemented with neuromodulation that provide the necessary flexibility for animals to move smoothly through their environment. This review will highlight some recent insights gained in understanding the functional dynamics and plasticity of the locomotor circuits. First the mechanisms governing the modulation of the speed of locomotion will be discussed. Second, advantages of the modular organization of the locomotor networks with multiple circuits engaged in a task-dependent manner will be examined. Finally, the neuromodulation and the resulting plasticity of the locomotor circuits will be summarized with an emphasis on endocannabinoids and nitric oxide. The intention is to extract general principles of organization and discuss some onto-genetic and phylogenetic divergences. © 2014 Elsevier Ltd.

Reig R.,Karolinska Institutet | Silberberg G.,Karolinska Institutet
Neuron | Year: 2014

The basal ganglia are involved in sensorimotor functions and action selection, both of which require the integration of sensory information. In order to determine how such sensory inputs are integrated, we obtained whole-cell recordings in mouse dorsal striatum during presentation of tactile and visual stimuli. All recorded neurons responded to bilateral whisker stimulation, and a subpopulation also responded tovisual stimulation. Neurons responding to both visual and tactile stimuli were located in dorsomedial striatum, whereas those responding only to whisker deflections were located dorsolaterally. Responses were mediated by overlapping excitation and inhibition, with excitation onset preceding that of inhibition by several milliseconds. Responses differed according to the type of neuron, with direct pathway MSNs having larger responses and longer latencies between ipsilateral and contralateral responses than indirect pathway MSNs. Our results suggest that striatum acts as a sensory "hub" with specialized functional roles for the different neuron types. © 2014 The Authors.

Kiehn O.,Karolinska Institutet
Current Opinion in Neurobiology | Year: 2011

The coordination and timing of muscle activities during rhythmic movements, like walking and swimming, are generated by intrinsic spinal motor circuits. Such locomotor networks are operational early in development and are found in all vertebrates. This review outlines and compares recent advances that have revealed the developmental and functional organization of these fundamental spinal motor networks in limbed and non-limbed animals. The comparison will highlight common principles and divergence in the organization of the spinal locomotor network structure in these different species as well as point to unresolved issues regarding the assembly and functioning of these networks. © 2010 Elsevier Ltd.

Currently used anticoagulants prevent thrombosis but increase bleeding. We show an anticoagulation therapy without bleeding risk based on a plasma protease factor XII function-neutralizing antibody. We screened for antibodies against activated factor XII (FXIIa) using phage display and demonstrated that recombinant fully human antibody 3F7 binds into the FXIIa enzymatic pocket. 3F7 interfered with FXIIa-mediated coagulation, abolished thrombus formation under flow, and blocked experimental thrombosis in mice and rabbits. We adapted an extracorporeal membrane oxygenation (ECMO) cardiopulmonary bypass system used for infant therapy to analyze clinical applicability of 3F7 in rabbits. 3F7 provided thromboprotection as efficiently as heparin, and both drugs prevented fibrin deposition and thrombosis within the extracorporeal circuit. Unlike heparin, 3F7 treatment did not impair the hemostatic capacity and did not increase bleeding from wounds. These data establish that targeting of FXIIa is a safe mode of thromboprotection in bypass systems, and provide a clinically relevant anticoagulation strategy that is not complicated by excess bleeding.

Human natural killer (NK) cells are functionally regulated by killer cell immunoglobulin-like receptors (KIRs) and their interactions with HLA class I molecules. As KIR expression in a given NK cell is genetically hard-wired, we hypothesized that KIR repertoire perturbations reflect expansions of unique NK-cell subsets and may be used to trace adaptation of the NK-cell compartment to virus infections. By determining the human "KIR-ome" at a single-cell level in more than 200 donors, we were able to analyze the magnitude of NK cell adaptation to virus infections in healthy individuals. Strikingly, infection with human cytomegalovirus (CMV), but not with other common herpesviruses, induced expansion and differentiation of KIR-expressing NK cells, visible as stable imprints in the repertoire. Education by inhibitory KIRs promoted the clonal-like expansion of NK cells, causing a bias for self-specific inhibitory KIRs. Furthermore, our data revealed a unique contribution of activating KIRs (KIR2DS4, KIR2DS2, or KIR3DS1), in addition to NKG2C, in the expansion of human NK cells. These results provide new insight into the diversity of KIR repertoire and its adaptation to virus infection, suggesting a role for both activating and inhibitory KIRs in immunity to CMV infection.

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