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WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

KI News

Updated: 1 hour 9 min ago

Karolinska Institutet launches new collaborations for innovation and research

Fri, 22/05/2015 - 08:08
Karolinska Institute’s wholly owned company, Karolinska Institutet Holding AB, has signed an agreement with Johnson & Johnson Innovation. The collaboration aims to strengthen innovation at Karolinska Institute and integrate it into product and business development, and implementation of health care. At the same time a research collaboration is established between Karolinska Institutet and Janssen Pharmaceuticals. As part of the collaboration, Johnson & Johnson Innovation will establish a life science innovation hub at Karolinska Institutet to work with Karolinska Institutet Holding AB, to support and drive the growth of life science companies rooted in academic medical research. Promising projects in the Nordic life science industry should be supported to develop services and products to support patients and consumers. The collaboration benefits between Karolinska Institutet Holding AB and Johnson & Johnson Innovation serves to meet the needs of entrepreneurs in the pharmaceutical, medical technology and healthcare sectors. It will include knowledge sharing, establishment of coaching and scouting programs, investments in developing ideas into finished concepts, and funding for start-ups. “One of the main missions of Karolinska Institutet is to help develop medical discoveries into innovations and products for the benefit of patients”, said Professor Anders Hamsten, vice-chancellor of Karolinska Institutet. “An important part of our strategy for the years to come is to establish collaborations with industry so as to strengthen innovation at our university and support corporate development from new discoveries and the implementation in health care. The collaborations with Johnson & Johnson Innovation and Janssen are an important step in that direction.” While launching this Karolinska Institutet collaboration with the pharmaceutical company Janssen Pharmaceuticals NV, one of the Janssen Pharmaceutical Companies of  Johnson & Johnson, a number of research posts have been created for observational studies (Real World Evidence). The focus of this cooperation is the follow-up and effects of disease and treatment, using routine data from health care ("Real World Data") and how they relate to effects in clinical trials, all while social and economic factors will be evaluated. The research will initially focus on method development, depression, prostate cancer, psoriasis, and cancers of the immune-system. The collaboration between Karolinska Institutet and Janssen will be led by Johan Askling, professor at the Department of Medicine in Solna. “We will, among other things, study the relationship between data from randomized trials and observational data from clinical practice, in order to increase understanding of how these can be made comparable, and how observational data can be used as an adjunct to clinical trial data” said Johan Askling.

Subconscious learning shapes pain responses

Fri, 22/05/2015 - 08:08
In a new study led from Karolinska Institutet, researchers report that people can be conditioned to associate images with particular pain responses – such as improved tolerance to pain – even when they are not consciously aware of the images.  The findings are being published in the journal PNAS. Previous studies have shown that a person’s pain experience can be increased or decreased by associating a specific cue, such as an image, with high or low intensity pain. However, until now it has been unclear if it is necessary to be consciously aware of the cue in order to learn the association. In this recent study, Dr. Karin Jensen and colleagues tested whether unconscious learning affected pain responses, by using subliminal images and training participants to associate a certain image with high pain and another image with low pain. The study involved 49 participants in all, randomly assigned into four experimental groups that would elucidate the impact of different levels of conscious awareness during the experiment. All participants were generally healthy, with no chronic illnesses or psychiatric diagnoses. None of the participants reported receiving any medication apart from hormonal contraceptives. In the experiment, images of different faces were presented on a computer screen. To some of the participants the images were shown so quickly that they could not be consciously recognized. For each image exposure, participants were subjected to pain stimulation and asked to rate the pain according to a specific scale. As each image was repeatedly associated with either high or low pain, it turned into a high pain cue or a low pain cue that would affect the participants’ expectations. Without conscious awareness The results suggest that pain cues could be learned without conscious awareness, as participants reported increased pain when shown the high pain image and reduced pain when shown the low pain image during identical levels of pain stimulation, regardless of whether or not the images were shown subliminally,  “These results demonstrate that pain responses can be shaped by learning that takes place outside conscious awareness, suggesting that unconscious learning may have an extensive effect on higher cognitive processes in general”, says Karin Jensen. This work was funded by the Osher Center for Integrative Medicine at Karolinska Institutet, and support was also provided by a NCCIH/NIH Grant. The study was conducted by researchers from the Osher Center at the Department of Clinical Neuroscience at Karolinska Institutet, Sweden and from Beth Israel Deaconess Medical Center and Harvard Medical School, USA. View our press release about this study Publication Classical conditioning of analgesic and hyperalgesic pain responses without conscious awareness Karin Jensen, Irving Kirsch, Sara Odmalm, Ted J. Kaptchuk, and Martin Ingvar PNAS, published ahead of print May 15, 2015, doi:10.1073/pnas.1504567112

Thomas Helleday elected to EMBO

Thu, 21/05/2015 - 15:15
As the only researcher active in Sweden out of a total 58, professor Thomas Helleday has been elected as a new member of EMBO 2015. EMBO – the European Molecular Biology Organization – is a very highly regarded European organisation which promotes quality in research in the field of life science. More than 1,700 leading researchers have been elected thus far, of which 50 are Swedish, and 24 of these from Karolinska Institutet. Read the press release from EMBO

Study questions beneficial effects of a Nordic diet on cardiovascular events

Thu, 21/05/2015 - 08:08
A new study led from Karolinska Institutet shows that although individual components of a healthy so-called Nordic diet previously have been linked to beneficial effects on cardiovascular health, as well as to other health effects, there is no evidence of an association with cardiovascular events in a general population. The study, which was conducted in in over 40,000 Swedish women, is being published in the Journal of Internal Medicine. Cardiovascular disease, such as heart attack and stroke, is a leading cause of death worldwide, and it has long been known that dietary factors have an important influence on cardiovascular health. Previous studies have shown beneficial effects of a healthy Nordic diet – comprising whole grain bread and oatmeal, fruit (apples/pears), vegetables (root vegetables and cabbage) and fish – on short-term markers of cardiovascular health, for example lower blood pressure and weight loss. Several studies have also showed beneficial effects of individual components included in the Nordic diet on cardiovascular events. However, the current study is the first to investigate the overall, long-term association between a healthy Nordic diet and the incidence of cardiovascular disease in the general population. The study was conducted in 43,310 middle-aged Swedish women. The participants answered questions in 1991/92 about their food intake, and the incidence of cardiovascular disease was recorded through the Swedish registries over approximately 20 years until the end of 2012. During the follow-up period, nearly 20% of the women developed cardiovascular disease. However, unexpectedly given the results of previous studies, the beneficial effect of a healthy Nordic diet did not register when looking at the incidence of concrete, cardiovascular events in the general population. “The reason for this for this discrepancy could be that previous studies showing effect of a healthy Nordic diet were intervention trials, which means participants had a very high adherence to this particular diet and also were selected, high-risk persons in relation to developing cardiovascular disease, whereas the present study expected a lesser degree of adherence, and looked and a group of overall healthy women”, says first author Nina Roswall, PhD, at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. Alcohol consumption or smoking An additional goal for the research team was to determine whether any relationship between the healthy Nordic diet and cardiovascular disease is modified by age, weight, alcohol consumption or smoking. Their results show that alcohol intake, weight (BMI) and age did not have any significant affect. “We did manage to show a beneficial effect of this diet among former smokers”, says Professor Elisabete Weiderpass, PhD, who supervised the study. “However, this may be due to the fact that smoking cessation is associated with dietary changes towards a healthier lifestyle, which may have affected the results. It is also important to point out that further investigation is required to confirm these findings.” Research organizations involved in this study, other than Karolinska Institutet, were the Danish Cancer Society Research Center, University of Auckland, New Zealand, Harvard School of Public Health, USA, Folkhälsan Research Center, Finland, The Cancer Registry of Norway, The Arctic University of Norway, and University of Tromsö, also in Norway. The investigation was supported by a grant from the Swedish Research Council. Publication No association between adherence to the healthy Nordic food index and cardiovascular disease among Swedish women – a cohort study Roswall Nina, Sandin Sven, Scragg Robert, Löf Marie, Skeie Guri, Olsen Anja, Adami Hans-Olov, Weiderpass Elisabete Journal of International Medicine, first published online 19 May 2015, DOI: 10.1111/joim.12378

The first Silvia doctors receive their diplomas from the Queen

Tue, 19/05/2015 - 15:15
“Now you can help to raise the life quality of these vulnerable patients and like flashing beacons spread your knowledge of dementia care,” said Karolinska Institutet’s vice-chancellor Anders Hamsten as he congratulated the first ever six doctors able to call themselves Silvia doctors. “I hope you all feel pride in what you’ve achieved.” Queen Silvia herself presented the diplomas to the six doctors who will now be bearing her name. The doctors have all taken a one-year’s Master’s programme in dementia care held jointly by Karolinska Institutet and the Silviahemmet Foundation, and received their diplomas at a degree ceremony at Drottningholm’s slottsteater. Also present was Minister for the Elderly, Åsa Regnér. In this unique 18th century theatre, with its orchestra in period garb and an audience from all over the world, the Queen talked of her own mother’s dementia and of how the difficulties giving and receiving proper care made her start the Silvia home, which has always trained Silvia sisters – nursing auxiliaries specialising in dementia – and Silvia nurses. Now there are also the first Silvia doctors, amongst them Moa Wibom, consultant and specialist in public health at Ängelholm Hospital. “These two years will be of benefit to us and our patients throughout our careers and our lives,” she says.   Text: Sara Nilsson Photo: Gustav Mårtensson

New knowledge about how type 2 diabetes develops

Tue, 19/05/2015 - 08:08
An international research team, led from Sweden’s Karolinska Institutet, have presented new knowledge about what happens when type 2 diabetes develops. By studying the insulin-producing beta cells in mice in real time, they have managed to identify a key part of the process that leads to the death of beta cells. The study is being published in the journal PNAS. Type 2 diabetes is characterised by two main events in the body. At the initial stage the cells become insulin-resistant, i.e. insensitive to insulin. At the next stage, the insulin-producing beta cells, which are located in the islets of Langerhans in the pancreas, die. Exactly how the disease develops is still unknown, but investigators at Karolinska Institutet and colleagues from Singapore and the USA have added another piece of the jigsaw. Ten years ago researchers at Karolinska Institutet discovered that blood levels of apolipoprotein CIII (apoCIII) become elevated in diabetes. This causes certain specific calcium channels in the beta cell wall to be overactivated which produces excessive calcium levels inside the beta cells. This has a toxic effect and results in beta cell death. However, the effect of apoCIII can be prevented by blocking the calcium channels. In the study in question, researchers have used insulin-resistant mice with type 2 diabetes. Because of the disease, the mice had elevated levels of apoCIII in their blood. This apoCIII was mainly produced in the liver although the islets themselves could also produce apoCIII as a consequence of local islet insulin resistance. Beta cell function and survival in real time The researchers then used a self-developed technique to transplant islets of Langerhans to the anterior eye chamber – a technique that makes it possible to study beta cell function and survival in real time. Normal islets of Langerhans which produce apoCIII were transplanted to one eye while genetically modified, non-apoCIII-producing islets were transplanted to the other eye. The researchers' main finding was that the beta cells reacted differently in each case. Despite the islets in both eyes being exposed to elevated levels of apoCIII circulating in the blood stream, only the apoCIII-producing islets showed an inflammatory reaction and, thereby, cell death. In the case of the genetically modified, non-apoCIII-producing islets, the beta cells survived. “This shows that local production of apoCIII has damaging effects on beta cells. Circulating apoCIII had no direct damaging effect on the beta cell under type 2 diabetic conditions,” says Lisa Juntti-Berggren, chief physician and professor at the Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery at Karolinska Institutet. Blocking the production of apoCIII locally The researchers are currently proceeding with animal studies to investigate the possibilities of blocking the production of apoCIII locally in islets of Langerhans. “Our goal is to develop a treatment strategy where you can prevent type 2 diabetes from developing in individuals with a high risk of the disease; people with insulin resistance, for example,” says Per-Olof Berggren, professor at the Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery at Karolinska Institutet. The study in question is funded by the Swedish Diabetes Association, Karolinska Institutet, Swedish Research Council, Novo Nordisk Foundation, Knut and Alice Wallenberg Foundation, Skandia insurance company, Diabetes Wellness Foundation, Bert von Kantzow Foundation, The Family Erling-Persson Foundation, The Swedish Diabetes Foundation, Lee Kong Chian School of Medicine, Nanyang Technological University Start-Up Grant, The Stichting af Jochnick Foundation and Diabetes Research Institute Foundation. Our press release about this study Publication Apolipoprotein CIII links islet insulin resistance to β-cell failure in diabetes Karin Åvall, Yusuf Ali, Ingo B. Leibiger, Barbara Leibiger, Tilo Moede, Meike Paschen, Andrea Dicker, Elisabetta Daré, Martin Köhler, Erwin Ilegems, Midhat H. Abdulreda, Mark Graham, Rosanne M. Crooke, Vanessa S. Y. Tay, Essam Refai, Stefan K. Nilsson, Stefan Jacob, Lars Selander, Per-Olof Berggren and Lisa Juntti-Berggren PNAS, 4 May 2015, doi: 10.1073/pnas.1423849112

Kerstin Tham proposed as new vice-chancellor of Malmö University

Mon, 18/05/2015 - 09:09
KI’s pro-vice-chancellor, Kerstin Tham, has been put forward as the new vice-chancellor of Malmö University, the only candidate to be considered by the university board following recommendation by its selection committee.   Kerstin Tham, who was made professor of occupational therapy at the Department of Neurobiology, Care Sciences and Society in 2009 and Karolinska Institutet’s pro-vice-chancellor in January 2013, is the selection committee’s proposal for Malmö University’s new vice-chancellor. The consultative assembly and union representatives at the university both unanimously recommend Kerstin Tham out of the three final candidates to have been selected through interviews and tests from a starting field of 69. Malmö University will be holding an extraordinary board meeting to decide the matter on 22 May, after we go to press. It is then up to the government to consider the university’s proposal and officially announce the appointment, although no final date has been given for when this will happen. This means that after two and a half years as pro-vice-chancellor of KI, Professor Tham has to make a decision on taking up a new office and that KI will probably need to start looking for her replacement. “I’ve learnt an incredible amount in my 20-years and more at Karolinska Institutet and now feel that it’d be interesting to put my experience and knowledge to use in a new context,” she says. “Malmö University is really Sweden’s largest university college, and I’m convinced that my experience from KI will come in useful in its ambition to obtain full university status.” The incumbent vice-chancellor, Stefan Bengtsson, will be leaving in August to become president and CEO of Chalmers University in Gothenburg.

Tuberculosis drug can improve effect of CBT

Mon, 18/05/2015 - 09:09
A new study from Karolinska Institutet shows that the effect of internet-based CBT (cognitive behavioural therapy) for people with people with obsessive-compulsive disorder (OCD) may be boosted with a drug called d-cycloserine, which has long been used to treat TB. According to the results, which are published in the journal JAMA Psychiatry, this enhancing effect is counteracted by antidepressants. “These types of drugs are sometimes called cognitive enhancers, as they affect specific brain processes that can speed up and boost the effects of psychotherapy,” says Dr Christian Rück, psychiatrist and researcher, who conducted the study with his colleagues at Karolinska Institutet’s Department of Clinical Neuroscience. “You could say that it’s to CBT what spinach is to Popeye.” The active therapeutic component of CBT is based on the concept of exposure or extinction, whereby the individual puts him/herself in feared situations that evoke feelings of discomfort or anxiety and remains there until the sensation wanes. D-cycloserine (DCS) is an old tuberculosis drug that also affects one of the brain’s most common receptors, the NMDA receptor. Previous studies have shown, for example, that DCS can amplify the effect of CBT if taken just prior to exposure to the fear-inducing stimulus. In the present study, the researchers tried adding DCS to online CBT for people with OCD. Previous research had shown that DCS can speed up the therapeutic effect of CBT for this disorder, but no study had been large enough to demonstrate lasting effects once the therapy has finished. The study randomly assigned 128 people with an OCD diagnosis to either a DCS or a placebo group. Also taking antidepressants The initial analysis indicated that while there was no difference between DCS and placebo, the effect of online CBT was considerable. In their subsequent analysis, the team therefore took into account whether the participants were also taking antidepressants. Doing so, they found that those not on antidepressants responded much better to DCS. “This tells us that the mechanism for DCS can be affected by antidepressants or vice versa and that it might one day be possible to use DCS and similar substances to boost the effect of CBT,” says Dr Rück. “Our study is the largest to date on DCS and OCD, but more research needs to be done to substantiate these positive effects and to fully understand and utilise the biological mechanisms behind effective CBT therapy.” The study’s first author is Erik Andersson, PhD. It was financed by grants obtained from the Swedish Research Council and through the ALF agreement between KI and the Stockholm County Council. More about the Rück lab Publication D-Cycloserine vs Placebo as Adjunct to Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction with Antidepressants; A Randomzed Clinical Trial Erik Andersson, Erik Hedman, Jesper Enander, Diana Radu Djurfeldt, Brjánn Ljótsson, Simon Cervenka, Josef Isung, Cecilia Svanborg, David Mataix-Cols, Viktor Kaldo, Gerhard Andersson, Nils Lindefors, Christian Rück JAMA Psychiatry, online 13 May 2015, doi: 10.1001/jamapsychiatry.2015.0546

Student from KI receives the Global Swede Award

Wed, 13/05/2015 - 19:19
Adeeb Tawseef, a student from the master's programme in bioentrepreneurship, is one of about 20 foreign students being given the Global Swede Award. The award ceremony will take place on 12 May with the awards handed out by the Minister for Enterprise and Innovation Mikael Damberg, together with the Swedish Institute' Director-General Annika Rembe. This is the fifth year in which this award has been given to foreign students studying in Sweden who have distinguished themselves within the fields of innovation and entrepreneurship. Adeeb Tawseef is studying for a master's degree in bioentrepreneurship at Karolinska Institutet and has previously gained a degree from the University of British Columbia in Vancouver, Canada. "What is especially significant for me is that it is not just Karolinska Institutet, but also the Government, that wants to highlight the contribution international students make to entrepreneurship and innovation. Karolinska Institutet has always encouraged me and the other students to get involved in these activities and I feel very honoured to be acknowledged like this", says Adeeb Tawseef. The number of students studying in other countries is increasing. In 2015, the number of international students in the world is estimated to be 4.3 million. "International exchanges and contacts mean a lot to Karolinska Institutet. While they are studying in Sweden these students also contribute to Swedish students' international perspective. International students also form relationships and networks that are important to both themselves and the contexts in which they will later be working", says Annika Östman Wernerson, Dead of Higher Education at Karolinska Institutet. The Global Swede Awards ceremony is a collaboration between the Swedish Institute and the Ministry for Foreign Affairs that aims to encourage the students to be ambassadors for Sweden. "The Global Swede Award is a way of promoting Swedish exports. By acknowledging top international students, valuable contacts are made which will benefit Swedish foreign trade in the long-term", says Minister for Enterprise and Innovation Mikael Damberg in a press statement. For more information, please view the Government offices website

Karolinska Institutet creates a new professorship in innovation and entrepreneurship

Wed, 13/05/2015 - 08:08
Karolinska Institutet has received a donation of 4 million USD, approximately 35 million SEK, for the creation of a professorship in innovation and entrepreneurship. The new professorship is financed by the 95-year-old doctor, researcher, innovator and business leader Professor Endre A. Balazs and his wife Dr Janet L. Denlinger. The “Endre A. Balazs Professorship in Innovation and Entrepreneurship” will now be advertised broadly. “The future incumbent could be a scientist, or an innovator and business leader with a PhD in the life science field,” says Dean of Research Hans-Gustaf Ljunggren. “We’re open to evaluate all kinds of candidates with strong profiles in the field.” The professor, who will be selected from an international field of competing applicants, will be expected to devote his or her time to research and education in the field of innovation and entrepreneurship. “An innovation culture is strategically important for Karolinska Institutet and for Swedish life science,” says the university’s vice-chancellor Anders Hamsten. “It’s part of our mission to help turn medical discoveries into innovations and products of use to the healthcare sector. We’re therefore extremely grateful for Endre Balazs’s generosity, as his donation opens up new, very exciting possibilities in this field.” Endre A. Balazs was a visiting researcher at Karolinska Institutet between 1947 and 1950, when he laid the foundation of a successful career as a scientist and entrepreneur. His ability to translate his research into commercial products has made him a wealthy man. In the 1940s, he managed to synthesize hyaluronic acid in large amounts from rooster combs. The substance is the base of a number of medical products, including Healon, which is an invaluable aid in lens transplants in cataract patients. Healon was licensed to Pharmacia in the early 1970s and was the company’s biggest product during the 1980s and 1990s. An estimated 300 million patients around the world have undergone cataract operations in which Healon and similar hyaluronic acid-based substances are used. Balazs and Denlinger later started the company Biomatrix and launched a product based on hyaluronic acid, which has been used for millions of patients suffering from arthrosis and other diseases of the joints.

How cancer tricks the lymphatic system into spreading tumours

Mon, 11/05/2015 - 12:12
Swollen lymph nodes are often the earliest sign of metastatic spread of cancer cells. Now cancer researchers and immunologists at Sweden’s Karolinska Institutet have discovered how cancer cells can infiltrate the lymphatic system by ‘disguising’ themselves as immune cells (white blood cells). The researchers hope that this finding, which is published in the scientific journal Oncogene, will inform the development of new drugs. The main reason why people die of cancer is that the cancer cells spread to form daughter tumours, or metastases, in vital organs, such as the lungs and liver. A route frequently used by cancer cells for dissemination is the lymphatic system. Upon entering lymphatic vessels, they migrate to nearby lymph nodes, which then swell up, and from there, to other organs via the blood. The details of how and why cancer cells use the lymphatic system for spread are, however, relatively unknown. “It’s not clear whether there are signals controlling this or whether it’s just random,” says principal investigator Jonas Fuxe, cancer researcher and Associate Professor at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics. “However, in recent years it has become evident that inflammation is a factor that can promote metastasis and that anti-inflammatory drugs may have a certain inhibitory effect on the spread of cancer.” The study is based on an interdisciplinary collaboration between cancer researchers and immunologists, which the researchers point out has has contributed to the new, exciting results. What they discovered was that an inflammatory factor known as TGF-beta (transforming growth factor-beta) can give cancer cells properties of immune cells by supplying the surface of the cancer cell with a receptor that normally only exists on the white blood cells that travel through the lymphatic system. New treatment models Equipped with this receptor, the cancer cells are able to recognise and migrate towards a gradient of a substance that is secreted from the lymphatic vessels and binds to the receptor. In this way, the cancer cells can effectively target lymphatic vessels and migrate on to lymph nodes, just like immune cells. According to the researchers, their results link inflammation and cancer in a novel way and make possible the development of new treatment models. “With this discovery in our hands, we’d now like to try to find out which additional immune-cell properties cancer cells have and study how they affect the metastatic process,” says Jonas Fuxe. “The possibility of preventing or slowing down the spread of cancer cells via the lymphatic system is an attractive one, as it could reduce the risk of metastasis to other organs.” Mikael Karlsson, Associate Professor and group leader at the Department of Microbiology, Tumour and Cell Biology at Karolinska Institutet was in charge of the immunological aspects of the study. In addition to the researchers at Karolinska Institutet, the study involved researchers from Umeå University, Sweden, Louisiana State University Health Sciences Centre and Princeton University in the USA and Nihon University School of Medicine in Tokyo, Japan. The study was financed by the Swedish Research Council, the Swedish Cancer Society, the Children’s Cancer Foundation, the Swedish Society for Medical Research (SSMF), Karolinska Institutet’s strategic research programme in cancer (StratCan), and the Nordic Cancer Union. Our press release about this research Publication  GF-β1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by activation of CCR7/CCL21-mediated chemotaxis  Mei-Fong Pang, Anna-Maria Georgoudaki, Laura Lambut, Joel Johansson, Vedrana Tabor, Kazuhiro Hagikura, Yi Jin, Malin Jansson, Jonathan S. Alexander, Celeste M. Nelson, Lars Jakobsson, Christer Betsholtz, Malin Sund, Mikael C. I. Karlsson & Jonas Fuxe Oncogene advance online publication 11 May 2015; doi: 10.1038/onc.2015.133

Ion pump gives the body its own pain alleviation

Mon, 11/05/2015 - 09:09
In a recent study, published in the journal Science Advances, researchers at Karolinska Institutet and Linköping University present a small ion pump in organic electronics that can stop pain impulses in living, freely moving rats by using the body’s own pain relief signals. This innovation gives new hope to people suffering from sever nerve pain for which no other cure yet has been found. The research team describes the implantable ion pump as a kind of pacemaker for alleviating pain, and estimate that it could be in clinical use in five to ten years.  However, while a pacemaker sends electrical impulses to the heart, the ion pump sends out the body’s own pain alleviator – charged molecules of what are known as neurotransmitters – to the exact place where the damaged nerves come into contact with the spinal cord. This means that the pain impulses never reach the brain. Organic electronics is a class of materials capable of easy translation between electronic and biochemical signals. In the current study, the device delivered the neurotransmitter γ-aminobutyric acid (GABA), whose natural task is to inhibit stimuli in our central nervous system. An electric current through the ion pump is all that is needed for the GABA neurotransmitter to be spread as a thin cloud at these exact locations on the spinal cord. So far, the pain alleviation has had no negative side effects, according to the researchers. The ion pump project is a part of a the OBOE multidisciplinary research center within organic bioelectronics, which includes ten research groups from Linköping Unviersity, Karolinska Institutet and Acreo Swedish ITC. Principal investigator at Linköping University was Professor Magnus Berggren, and head of the preclinical part of the project at Karolinska Instiutet was professor Bengt Linderoth. This work was funded by VINNOVA, the Knut and Alice Wallenberg Foundation, and the Swedish Research Council, amongst others. Read more in a press release from Linköping University Publication Therapy using implanted organic bioelectronics Amanda Jonsson, Zhiyang Song, David Nilsson, Björn A. Meyerson, Daniel T. Simon, BengtLinderoth, Magnus Berggren Science Advances 8 May 2015, Vol. 1 no. 4 e1500039, DOI: 10.1126/sciadv.1500039

Her mission: the world

Fri, 08/05/2015 - 14:14
She is the new deputy vice-chancellor for international affairs at Karolinska Institutet and wants to make KI’s global role more prominently defined, both internally and internationally. Meet Maria Masucci in interview with KI News. “Globalisation brings exciting developments in all areas, so it’s obvious that the university has an important part to play,” says Maria Masucci, professor of virology at Karolinska Institutet and the university’s deputy vice-chancellor for international affairs since May 1. Above all, she wants to contribute to the initiative that the university management launched in its Strategy 2018, which has a strong focus on internationalisation. Sweden is a small country, but research knows no national borders. Collaboration is possible thanks to new technology and communication, says Professor Masucci, as well as student exchanges, which must be made easier and more effective. “There are already many different initiatives at KI and I’m not intending to reinvent the wheel,” she says, adding that these initiatives can, however, be made more structured in order to provide an overview of the situation. It must be made clear where KI can be found in the world, and that the world can be found at KI.     Read more in a pressrelease.

Gene variant determines early or late onset of Huntington’s disease

Tue, 05/05/2015 - 08:08
Researchers at Karolinska Institutet and the University of British Columbia, Canada, have identified a gene variant that influences whether Huntington’s disease breaks out earlier or later than expected. The findings, which are published in the scientific journal Nature Neuroscience, can contribute to improved diagnosis and disease-modifying therapies. A typical symptom of the inherited, progressive, neurodegenerative Huntington’s disease is involuntary movements. While the symptom normally debuts in middle-age, there is wide individual variation in how the disease manifests itself, and even though two people carry the exact same genetic mutation that codes for the huntingtin protein, there can be up to a 20-year difference in onset. Scientists have now discovered a small genetic change just outside the huntingtin gene that exchanges one base in the DNA molecule for another and that they think plays an important part in this phenomenon. “We’ve identified for the first time a gene variant that affects the onset of the disease,” says principal investigator Dr Kristina Bečanović from Karolinska Institutet’s Department of Clinical Neuroscience. “What’s interesting is that we managed to show that it can both delay and accelerate the development of the disease depending on which gene copy it sits on.” Most people who develop Huntington’s disease have a normal and a mutated huntingtin gene. In the present study, the researchers found that when the gene variant was on the gene copy that codes for the normal huntingtin protein, the patients developed motor symptomson average four years earlier than expected; on the other hand, the gene variant had a protective effect when sitting on the gene copy that codes for the mutated protein, which is toxic for the brain. These patients developed their motor symptoms on average ten years later than expected. Explains the differences The researchers also found that a transcription factor, NF-kappaB , activates the huntingtin gene, but also that the gene variant makes it harder for NF-kappaB to activate the expression of huntingtin. The study suggests that the gene variant therefore leads to lower levels of the normal or the mutated protein depending on which gene copy it sits on, and that this explains the differences in disease onset. “Our findings are extremely important to the development of disease-modifying treatments, which not only reduce the symptoms but also protect the brain,” says Dr Bečanović. “For example, much research has gone into silencing the expression of the huntingtin protein, something that will be tested in patients within the near future. Our work is the first to support the claim that this type of therapy could help people with Huntington’s disease by slowing the progress of the disease.” “The study offers a smorgasbord of ideas for new therapies, and is the very successful outcome of a genuinely translational and international collaboration between preclinical researchers and clinicians,” says Dr Ola Hermanson from Karolinska Institutet’s Department of Neuroscience, one of the co-authors. The study was financed with grants from several bodies, including the Swedish Research Council, and involved researchers from Karolinska Institutet, the University of British Columbia (Canada), Copenhagen University (Denmark), University College London (UK) and the University of Iowa (USA).  View our press release about this study Publication A SNP in the HTT promoter alters NF-kB binding and is a bidirectional genetic modifier of Huntington disease Kristina Bečanović, Anne Nørremølle, Scott J Neal, Chris Kay, Jennifer A Collins, David Arenillas, Tobias Lilja, Giulia Gaudenzi, Shiana Manoharan, Crystal Doty, Jessalyn Beck, Nayana Lahiri, Elodie Portales-Casamar, Simon C Warby, Colúm Connolly, Rebecca A G DeSouza, REGISTRY Investigators of the European Huntington’s Disease Network, Sarah J Tabrizi, Ola Hermanson, Douglas R Langbehn, Michael R Hayden, Wyeth W Wasserman & Blair R Leavitt Nature Neuroscience, online 4 May 2015, doi: 10.1038/nn.4014

New insights into ‘DNA parasites’ and genomic stability

Mon, 04/05/2015 - 17:17
A study led by newly recruited faculty Simon Elsässer at Karolinska Institutet/SciLifeLab shows that a specialized histone protein, one of the abundant molecules responsible for packaging our DNA in the cell nucleus, maintains genomic stability by silencing 'parasitic' DNA-elements. The study was published in Nature. Simon Elsässer joined Karolinska Institutet and the SciLifeLab in the beginning of 2015, from the MRC Laboratory of Molecular Biology, Cambridge, UK. In his research, he focuses on applying new synthetic and chemical biology methods to understand chromatin structure and function. Publishing in Nature, together with colleagues at the Rockefeller University in New York, USA he has now elucidated the mechanism of how certain DNA elements in mouse cells are silenced. These 'parasitic' DNA elements called transposons can jump and multiply within a host genome and have played an active role in animal evolution, facilitating genetic variation and adaptation. But their activity represents a threat to the host genome and thus they are almost always actively repressed, or silenced, by various proteins and regulatory RNAs produced by the host genome. Simon Elsässer’s team has found a new factor that is used to mark specific DNA elements that should be silenced. It is a protein called histone H3.3, a variant of the canonical histone H3. Histones are proteins that wrap our DNA like strings on beads and facilitate packing of DNA 10 000 fold to fit in the cell nucleus. Through this packaging mechanism, researchers think that histone proteins are the key to regulating access to the genetic information by making different parts of the DNA accessible to factors that express the gene, so-called epigenetic regulation. “Histone proteins carry a large number of distinct hemical modifications or ‘marks’, providing a verbose epigenetic language,” says Simon Elsässer. “As a field, we have only started to appreciate the intricate complexity of this histone code. It has been appreciated in the last decade that, just like errors in the genetic language itself, failure to maintain the epigenetic information can cause human disease, such as developmental disorders or cancer". Exceptionally strong signal H3.3 has been intensely studied in other processes, but until now no one has looked at transposable elements. Unexpectedly, the current study shows that a large fraction of H3.3 occupies transposable elements in the mouse embryonic stem cells and that it is required to permanently silence the underlying DNA elements. The combination of H3.3 and a known silencing mark – histone H3 lysine 9 trimethylation (which in no other instance are found together) – provides an exceptionally strong signal to the cell to 'not read from this genomic region'. When Simon Elsässer’s team deleted all H3.3 genes, they found that certain previously silenced transposable elements were reactivated and continued to multiply in the genome; the result is the appearance of new genetic alleles and chromosomal abnormalities, both are familiar early events in the formation of tumors. The researchers think that, while different types of transposable elements are prevalent in humans, the same mechanism may be in action in human cells. Over the last few years a number of cancer types have been found to harbor frequent and recurrent mutations in the histone variant H3.3.  The study has been funded by grants from the Rockefeller University Fund, the Tri-Institutional Stem Cell Initiative, and the Cambridge University Herchel Smith Fund. Read more about this research on the website of SciLifeLab  View a press release from Rockefeller University Publication Histone H3.3 is required for endogenous retroviral element silencing in embryonic stem cells Simon J. Elsässer, Kyung-Min Noh, Nichole Diaz, C. David Allis, Laura A. Banaszynski Nature, online 4 May 2015, doi: 10.1038/nature14345

Brain scan reveals out-of-body illusion

Thu, 30/04/2015 - 18:18
The feeling of being inside one’s own body is not as self-evident as one might think. In a new study from Sweden’s Karolinska Institutet, neuroscientists created an out-of-body illusion in participants placed inside a brain scanner. They then used the illusion to perceptually ‘teleport’ the participants to different locations in a room and show that the perceived location of the bodily self can be decoded from activity patterns in specific brain regions. The sense of owning one’s body and being located somewhere in space is so fundamental that we usually take it for granted. To the brain, however, this is an enormously complex task that requires continuous integration of information from our different senses in order to maintain an accurate sense of where the body is located with respect to the external world. Studies in rats have shown that specific regions of the brain contain GPS-like 'place cells' that signal the rat’s position in the room – a discovery that was awarded the 2014 Nobel Prize in Physiology or Medicine. To date, however, it remains unknown how the human brain shapes our perceptual experience of being a body somewhere in space, and whether the regions that have been identified in rats are involved in this process. In a new study, published in the scientific journal Current Biology, the scientists created an out-of-body illusion in fifteen healthy participants placed inside a brain scanner. In the experiment, the participants wore head-mounted displays and viewed themselves and the brain scanner from another part of the room. From the new visual perspective, the participant observes the body of a stranger in the foreground while their physical body is visible in the background, protruding from the bore of the brain scanner. To elicit the illusion, the scientist touches the participant’s body with an object in synchrony with identical touches being delivered to the stranger’s body, in full view of the participant. “In a matter of seconds, the brain merges the sensation of touch and visual input from the new perspective, resulting in the illusion of owning the stranger’s body and being located in that body’s position in the room, outside the participant’s physical body,” says Arvid Guterstam, lead author of the present study. Different places in the scanner room In the most important part of the study, the scientists used the out-of-body illusion to perceptually ‘teleport’ the participants between different places in the scanner room. They then employed pattern recognition techniques to analyze the brain activity and show that the perceived self-location can be decoded from activity patterns in specific areas in the temporal and parietal lobes. Furthermore, the scientists could demonstrate a systematic relationship between the information content in these patterns and the participants’ perceived vividness of the illusion of being located in a specific out-of-body position. “The sense of being a body located somewhere in space is essential for our interactions with the outside world and constitutes a fundamental aspect of human self-consciousness,” says Arvid Guterstam. “Our results are important because they represent the first characterization of the brain areas that are involved in shaping the perceptual experience of the bodily self in space.” One of the brain regions from which the participants’ perceived self-location could be decoded was the hippocampus – the structure in which the Nobel Prize awarded ´'place cells' have been identified. “This finding is particularly interesting because it indicates that place cells are not only involved in navigation and memory encoding, but are also important for generating the conscious experience of one’s body in space,” says principal investigator Henrik Ehrsson, professor at the Department of Neuroscience, Karolinska Institutet. This study was made possible by funding from amongst others the Swedish Research Council, the James McDonnell Foundation, and Riksbankens Jubileumsfond. Our press release about this research View a short movie illustrating these experiments Publication Posterior Cingulate Cortex Integrates the Senses of Self-location and Body Ownership Arvid Guterstam, Malin Björnsdotter, Giovanni Gentile & Henrik Ehrsson Current Biology, online 30 April 2015, doi: http://dx.doi.org/10.1016/j.cub.2015.03.059

Bottleneck analysis can improve care for mothers and newborns in poor settings

Thu, 30/04/2015 - 14:14
In a study published in the Bulletin of the World Health Organization, researchers from universities including Karolinska Institutet present a new model for identifying 'bottlenecks' when it comes to implementing health interventions for mothers and newborns in rural areas in low income countries The study is based on information from households and health facilities in two rural areas in Tanzania, East Africa. The researchers investigated five health interventions that can contribute to reduce mortality among mothers and newborns when implemented as intended: screening for syphilis and preeclampsia, monitoring child birth using a partogram, active management of the third stage of labour and care of the mother during the first two days after delivery. By analysing the implementation chain, they were able to estimate the proportion of mothers and newborns in the two areas who received these health interventions and in what way. They could also get an idea of which deficiencies caused the potential bottlenecks. “We show that, despite more frequent use of health care, even in rural areas in Tanzania, the proportion of mothers and newborns who receive life-saving health interventions is still small”, says lead author Dr Ulrika Baker, a doctoral student at Karolinska Institutet. “Bottlenecks can be caused by lack of drugs or deficient clinical practice and our study shows how these bottlenecks vary considerably between nearby areas.” Further efforts are needed  One conclusion made by the researchers is that further efforts are needed to facilitate access to and use of local data in order to improve health and medical care in low-resource settings. How coverage of health interventions is defined and measured is crucial to be able to prioritise efforts to reduce mortality among mothers and newborns. “A bottleneck analysis provides deeper insights into why certain things don’t work, that is more information than just stating that a certain proportion of the population isn’t reached by a health intervention”, says Professor Stefan Swartling Peterson, one of the researchers behind the study. “The results therefore become more useful for planning purposes. It is true that there is a great lack of many things, but it is also a matter of what health workers do with the available resources.” “We need to shift our focus from increasing access to care to increasing quality of care in low income countries”, says Dr Claudia Hanson, postdoc, who supervised the study. “With improved communication and development, poor quality of health care becomes the largest barrier for improved health and reduced mortality.” The work has been finances with funds from the Seventh Framework Programme of the European Community, through the project EQUIP, Stockholm County Council and Karolinska Institutet. Ulrika Baker, Claudia Hanson and Stefan Peterson are all affiliated to the Department of Public Health Sciences at Karolinska Institutet.  Publication Identifying implementation bottlenecks for maternal and newborn health interventions in rural districts of the United Republic of Tanzania Ulrika Baker, Stefan Peterson, Tanya Marchant, Godfrey Mbaruku, Silas Temu, Fatuma Manzi & Claudia Hanson Bulletin of the World Health Organization, online 22 April 2015, Article ID: BLT.14.141879  

KI high up on world university rankings for different subjects

Thu, 30/04/2015 - 08:08
Karolinska Institutet is well-placed on the international “QS world university rankings by subject”. The results are based on reputation surveys and citation data, and are a breakdown of the more general rankings published last autumn, which placed KI 8th in Life Sciences & Medicine field. KI has results in 15 defined subject fields and has been listed in six different disciplines. Examples of KI’s rankings are Medicine: 9th in the world; Pharmacy & Pharmacology: 6th; and Dentistry (new for 2015): 1st. For this subject, however, comparisons are difficult to make, partly due to the lack of results from previous years. Find more about QS World University Rankings by Subject 2015.    

Key factor in the neural death that causes Parkinson’s identified

Tue, 28/04/2015 - 13:13
A team of scientists from Karolinska Institutet and Ludwig Cancer Research has discovered how disruption of a developmental mechanism in the brain alters the very nerve cells that are most affected in Parkinson’s disease. The study, which is being published in the journal Nature Neuroscience, also explains how this disruption induces a lethal dysfunction in the internal, house-keeping processes of such neurons. An incurable neurological disorder, Parkinson’s disease (PD) typically begins in patients as a mere tremor and progresses to a debilitating loss of control over movement and cognitive dysfunction, eventually leading to dementia and death. These symptoms are caused by the gradual wasting away of dopaminergic (DA) neurons, which respond to the neurotransmitter dopamine and are primarily clustered in the midbrain. The causes of their wholesale death in PD, however, remain something of a mystery. In the current study, led by Professor Thomas Perlmann, researchers investigated a pair of closely related transcription factors – Lmx1a and Lmx1b – which are involved in the development of DA neurons. These developmentally vital transcription factors persist even after the neurons have matured. To find out what they do in mature neurons, the researchers painstakingly engineered mice in a manner that permitted them to delete the Lmx1a/b genes in DA neurons alone, and to do so at a time of their choosing. “When we looked at the DA neurons that lacked the Lmx1a/b genes, those in adult mice had many of the same abnormalities you see in various stages of PD,” says Thomas Perlmann. "The engineered mice were also shown in behavioral tests to have poor memory and motor control, both of which are symptoms of PD.” Affecting the neurons The team found that midbrain DA neurons from patients with PD express far lower levels of the Lmx1b protein than do their non-PD counterparts. So the researchers looked into how the loss of Lmx1a and b was affecting the neurons. They found that Lmx1b, in particular, controls the expression of a number of genes central to a process known as lysosomal autophagy by which cells break down abnormally folded protein molecules so that they don’t poison the cell. This process is believed to be compromised in PD. Treating young mice with a compound that boosts autophagy reversed the neural degeneration induced by loss of Lmx1b. In sum, the studies suggest the loss of Lmx1b expression is probably involved in the development of PD, that it induces a decline in the function of DA neurons by undermining autophagy and that this gradually sickens and then kills the DA neuron. This study was supported by Ludwig Cancer Research, the European Union’s Seventh Framework Programme, the Swedish Strategic Research Foundation, the Swedish Research Council, Hjärnfonden and Parkinsonfonden. This news article is an abbreviated version of a press release from Ludwig Cancer Research. Publication Dopaminergic control of autophagic-lysosomal function implicates Lmx1b in Parkinson's disease Ariadna Laguna, Nicoletta Schintu, André Nobre, Alexandra Alvarsson, Nikolaos Volakakis, Jesper Kjaer Jacobsen, Marta Gómez-Galán, Elena Sopova, Eliza Joodmardi, Takashi Yoshitake, Qiaolin Deng, Jan Kehr, Johan Ericson, Per Svenningsson, Oleg Shupliakov & Thomas Perlmann Nature Neuroscience, AOP 27 April 2015, doi: 10.1038/nn.4004

Scientists create the sensation of invisibility

Thu, 23/04/2015 - 15:15
The power of invisibility has long fascinated man and inspired the works of many great authors and philosophers. In a study from Sweden’s Karolinska Institutet, a team of neuroscientists today reports a perceptual illusion of having an invisible body and show that the feeling of invisibility changes our physical stress response in challenging social situations. The history of literature features many well-known narrations of invisibility and its effect on the human mind, such as the myth of Gyges’ ring in Plato’s dialogue The Republic and the science fiction novel The Invisible Man by H.G. Wells. Recent advances in materials science have shown that invisibility cloaking of large-scale objects, such as a human body, might be possible in the not-so-distant future; however, it remains unknown how invisibility would affect our brain and body perception. In an article in the journal Scientific Reports, the researchers describe a perceptual illusion of having an invisible body. The experiment involves the participant standing up and wearing a set of head-mounted displays. The participant is then asked to look down at her body, but instead of her real body she sees empty space. To evoke the feeling of having an invisible body, the scientist touches the participant’s body in various locations with a large paintbrush while, with another paintbrush held in the other hand, exactly imitating the movements in mid-air in full view of the participant. “Within less than a minute, the majority of the participants started to transfer the sensation of touch to the portion of empty space where they saw the paintbrush move and experienced an invisible body in that position,” says Arvid Guterstam, lead author of the present study. “We showed in a previous study that the same illusion can be created for a single hand. The present study demonstrates that the ‘invisible hand illusion’ can, surprisingly, be extended to an entire invisible body.” Make a stabbing motion The study examined the illusion experience in 125 participants. To demonstrate that the illusion actually worked, the researchers would make a stabbing motion with a knife toward the empty space that represented the belly of the invisible body. The participants’ sweat response to seeing the knife was elevated while experiencing the illusion but absent when the illusion was broken, which suggests that the brain interprets the threat in empty space as a threat directed toward one’s own body. In another part of the study, the researchers examined whether the feeling of invisibility affects social anxiety by placing the participants in front of an audience of strangers. “We found that their heart rate and self-reported stress level during the ‘performance’ was lower when they immediately prior had experienced the invisible body illusion compared to when they experienced having a physical body,” says Arvid Guterstam. “These results are interesting because they show that the perceived physical quality of the body can change the way our brain processes social cues.” The researches hope that the results of the study will be of value to future clinical research, for example in the development of new therapies for social anxiety disorder.   “Follow-up studies should also investigate whether the feeling of invisibility affects moral decision-making, to ensure that future invisibility cloaking does not make us lose our sense of right and wrong, which Plato asserted over two millennia ago,” says principal investigator Dr. Henrik Ehrsson, professor at the Department of Neuroscience. This research was funded by the Swedish Research Council, and the Söderberg Foundation. View our press release about this research Publication Illusory ownership of an invisible body reduces autonomic and subjective social anxiety responses Arvid Guterstam, Zakaryah Abdulkarim & Henrik Ehrsson Scientific Reports online 23 April 2015, doi: doi: 10.1038/srep09831

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