Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
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DEPARTMENT OF MEDICAL
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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 59 min ago

New therapeutic principle for Parkinsonian dyskinesia shows clinical effect

Tue, 10/02/2015 - 12:12
Involuntary dyskinetic movements induced by treatment with levodopa (L-dopa) are a common problem for people with Parkinson’s disease. Now, however, researchers at Karolinska Institutet and Lund Universityseem to be close to a novel therapy to this distressing side effect. A treatment study published in the journal Brain shows that a drug that stimulates certain serotonin receptors in the brain counteracts the dyskinesia causing effects of L-dopa. The substance tested by the team, eltoprazine, is a so-called serotonin receptor agonist that targets receptor types 5-HT1A and 5-HT1B. Serotonin is a neurotransmitter involved in the regulation of many biological phenomena, such as satiation, sleep and mental wellbeing, as well as movement. Earlier research on animal models for Parkinson’s conducted by Anders Björklund, professor of histology at Lund University, and Per Svenningsson, professor of neurology at Karolinska Institutet, showed promising results using serotonin receptor agonists against L-dopa-induced hyperkinesia, and have prompted the researchers to examine if the principle also operates in humans. “Eltoprazine has been tested on patients in the psychiatric field, but this is the first time a study has been done with Parkinson’s disease,” says professor Svenningsson, who led the clinical study with Håkan Widner, professor of neurology, from Lund University. “What’s particularly exciting is that we’ve managed to translate laboratory findings into clinical application.”  Four-way crossover study The study included 22 patients with protracted and complicated Parkinson’s disease and L-dopa-induced dyskinesia. In the four-way crossover study, patients were given a single tablet of placebo and eltoprazine 2.5, 5 and 7.5 mg, alongside a challenge dose of levodopa that was 1.5 times that of their usual L-dopa dose. It was found that a 5 mg and 7.5 mg dose of eltoprazine both significantly reduced the patients’ dyskinesia. At the same time, the preparation had no adverse impact on the anti-Parkinsonian effects of the L-dopa treatment. Other than a few patients having some transient episodes of nausea, dizziness and other minor symptoms the treatment was well tolerated. “The treatment seems to be tolerated well by most Parkinson’s patients and counteracts L-dopa-induced dyskinesia via a new mechanism of action,” says Professor Svenningsson. “If our initial findings can be confirmed, this type of therapeutic principle can be of immense clinical benefit to a particularly vulnerable patient group.” Since the 1990s Even though eltoprazine has been around since the 1990s, it still has not been registered, and the combination study reported here was done on the initiative of the lead investigators themselves. The study was partly financed with a grant from the Michael J. Fox Foundation for Parkinson's research. Recently, however, the rights to eltoprazine were acquired by the US biotechnology company Amarantus BioScience Holdings, Inc. The compound is now advancing into a larger scale, longer duration study to evaluate the full treatment effect of eltoprazine in Parkinson’s patients with L-dopa-induced dyskinesia. Professor Svenningsson is affiliated to Karolinska Institutet's Department of Clinical Neuroscience, and to the Center for Molecular Medicine. He is also a specialist physician at the Karolinska University Hospital.  View our press release about this study Publication Eltoprazine counteracts L-dopa-induced dyskinesias in Parkinson's disease: A dose-finding study Per Svenningsson, Carl Rosenblad, Karolina af Edholm Arvidsson, Klas Wictorin, Charlotte Keywood, Bavani Shankar, David A. Lowe, Anders Björklund, Håkan Widner Brain – A Journal of Neurology, first online 10 February 2015

Novo Nordisk and Karolinska Institutet join forces in the field of diabetes

Tue, 10/02/2015 - 11:11
Karolinska Institutet and Novo Nordisk today signed a collaboration agreement in the field of diabetes. The programme will be fully funded by Novo Nordisk. In the new international post-doctoral fellowship programme, a total of 12 post-doctoral researchers will be offered a three-year grant to support their research primarily within the field of diabetes and metabolism. The research will be performed at Karolinska Institutet in Stockholm, Sweden, but there will also be possibility for research exchange performed at Novo Nordisk Research and Development in Denmark. “Novo Nordisk is the world leader in diabetes research and insulin, and this initiative is of strategic importance both to them and to us,” said Professor Anders Hamsten, vice-chancellor at Karolinska Institutet. “The agreement creates a unique opportunity for recruiting young diabetes researchers to Karolinska Institutet. In a comment to the collaboration agreement, Mads Krogsgaard Thomsen, executive vice president and chief science officer at Novo Nordisk, said: “Together, we will train scientists in exploring basic diabetes research and translating this into new potential treatments for patients. Building upon the unique academic and clinical tradition at Karolinska Institutet and our company’s excellence in research and development, the collaboration holds great potential to stimulate innovation and ultimately to improve the lives of the patients”. Novo Nordisk has research and development facilities in Denmark, US, China and India. More than 7,000 employees are involved in research and development activities, many of them working in partnerships with external biotech and academic researchers. “This agreement is yet another example of Karolinska Institutet’s ambition to strengthen collaboration with the business community, in this case Novo Nordisk, one of the leading pharmaceutical companies in the Nordic region,” said Professor Hans-Gustaf Ljunggren, dean of research at Karolinska Institutet. A joint steering committee with members from both Karolinska Institutet and Novo Nordisk will oversee the programme and will be responsible for recruiting researchers. The first four fellows in the programme are expected to start in the autumn of 2015.

Recent infections may curb risk of rheumatism

Thu, 05/02/2015 - 10:10
Recent gut and urinary tract infections may curb the risk of developing rheumatoid arthritis, suggests a new study from Karolinska Institutet published online in the journal Annals of the Rheumatic Diseases. According to the researchers, one possible explanation could lie in the way in which these infections alter the types of bacteria resident in the gut (microbiome). The research team set out to look at the impact of different types of infection on the risk of developing rheumatoid arthritis in almost 6500 people living in south and central Sweden. Of the entire sample, 2831 had been newly diagnosed with rheumatoid arthritis between 1996 and 2009. The remaining 3570, who were randomly selected from the population, were healthy, but matched for age, sex, and area of residence with the patients. The average age of all participants at study entry was 52, and 7 out of 10 of them were women. All participants were asked whether they had had any gut, urinary tract, or genital infections in the preceding two years. They were also asked if they had had prostatitis (inflamed prostate), or antibiotic treatment for sinusitis, tonsillitis/other throat infection, or pneumonia during this time. Significantly lowered risk  Gut, urinary tract, and genital infections within the preceding two years were each associated with a significantly lowered risk of developing rheumatoid arthritis: 29 percent, 22 percent, and 20 percent, respectively. Further, having all three types of infection in the preceding two years was linked to a 50 percent lower risk, after taking account of influential factors.  By contrast, no such associations were found for recent respiratory infections and pneumonia. Factoring in smoking and socioeconomic background made no difference to the overall findings. However, since this is an observational study researchers point out that no definitive conclusions can be drawn about cause and effect. Lead author of the current study is Maria Sandberg, PhD, at Karolinska Institutet’s Institute of Environmental Medicine . The work was financially supported by grants from the Swedish Medical Research Council, the Swedish Research Council for Health, Working Life and Welfare, the AFA foundation, Vinnova, King Gustaf V’s 80-year foundation, the Swedish Rheumatic Foundation, and the Swedish Foundation for Strategic Research.  This news article is an adapted version of a press release from BMJ Journals. Publication Recent infections are associated with decreased risk of rheumatoid arthritis –a population-based case-control study Maria EC Sandberg, Camilla Bengtsson, Lars Klareskog, Lars Alfredsson, Saedis Saevarsdottir Annals of the Rheumatic Diseases, online first 5 February 2015,  doi 10.1136/annrheumdis-2014-206493

Mutual benefit from partnership between KI and Makerere University

Wed, 04/02/2015 - 07:07
For low-income countries it is necessary to improve national research quality and capacity, and one way of doing this is through partnership with universities in high-income countries. However, the benefit of this kind of academic collaboration is mutual, according to the authors of a recent article in PLOS Medicine, in which they present the long-term partnership between Karolinska Institutet and Makerere University in Uganda. The collaboration between Karolinska Institutet and Makerere University started in 2001 and includes amongst other things the possibility for students to receive a novel joint PhD degree from both universities.  To date, 28 such joint degrees have been awarded. In all, the partnership has resulted in 44 graduated PhD students, of which 11 were from Sweden and 33 from Uganda, and over 500 peer-reviewed articles have been published in scientific journals. “The program makes it possible for PhD students to spend most of their time at the home university, travelling abroad not more than two or three months per year”, said Stefan Peterson, Professor of Global Health at Karolinska Institutet. “This has been beneficial to students with young children, and has served to minimize so called brain drain from Uganda. All Ugandan PhD graduates have remained in the country and thirteen of them have embarked on postdoc training.” Ugandan health system priorities This collaboration effort was enabled by core support from the Swedish Sida, and has mainly addressed Ugandan health system priorities. It has resulted in policy and practice reforms concerning improved mother and child health care in Uganda, also benefitting other African countries by means of WHO and UNCEF policy changes. “The research projects have focused on everything from mental health to Malaria”, said Stefan Peterson. “We are just starting a new study on diabetes and health systems, where the Swedish health system will learn from the Ugandan how to use community resources and expert patients to change lifestyles, rather than going to your GP.” According to Stefan Peterson, Sweden has a unique possibility through joint PhDs to contribute to a sustainable global development by supporting PhD education focusing on local problem issues in low-income countries and global health issues. This will also to benefit Sweden: “The world is one, and Swedish students, lecturers and scientist have a lot to learn”, said Stefan Peterson. “Not only Sida and the Swedish Foreign Ministry can benefit, but the Ministry of Higher Education as well, and should fund these kind of efforts. “ More about Karolinska Institutet's collaboration with Uganda Publication Enabling Dynamic Partnerships through Joint Degrees between Low- and High-Income Countries for Capacity Development in Global Health Research: Experience from the Karolinska Institutet/Makerere University Partnership Nelson Sewankambo, James K. Tumwine, Göran Tomson, Celestino Obua, Freddie Bwanga, Peter Waiswa, Elly Katabira, Hannah Akuffo, Kristina Persson, Stefan Peterson PLOS Medicine, online 3 February 2015, doi: 10.1371/journal.pmed.1001784

New facilities at SciLifeLab makes way for advanced cell analyses

Tue, 03/02/2015 - 14:14
Three new facilities for single cell biology are being set up at SciLifeLab in Stockholm and Uppsala during spring 2015. The new facilities will render technological advances in Sweden and abroad widely available to the Swedish scientific community, with the goal for the region to become world leading in advanced molecular single cell analyses. Advances in cell sorting and molecular analyses now enable researchers to comprehensively describe properties and functions of individual cells. This is in contrast to conventional biochemistry and molecular biology, which focuses on analyses of whole tissue samples and whole microbial populations or communities. The three new single cell-facilities will be integrated in the SciLifeLab national platform Functional Genomics. The facilities build on unique expertise that will allow Swedish researchers to capitalize on recent technological advances to characterize individual cells at genomic, transcriptomic, and proteomic levels. The aim is to provide new insights into heterogeneity and division of labor within tissues or communities of cells from all domains of life. “Single cell genomics can be applied to understand the heterogeneity of tumors, to explain how genetically identical cells may show distinct behavior, and to explore the vast, uncharacterized microbial landscape. Therefore, these technologies have the potential to revolutionize biology and medicine.” says Sten Linnarsson, Senior Researcher at Karolinska Institutet and Platform Director of the Eukaryotic Single-Cell Analysis facility. Read more here

Hong Kong-based businessman Ming Wai Lau donates USD 50 million to Karolinska Institutet

Mon, 02/02/2015 - 09:09
Karolinska Institutet is to set up its own research base in Hong Kong. This is made possible by a donation of USD 50 million, equivalent to SEK 400 million made by Hong Kong-based businessman Ming Wai Lau. The Ming Wai Lau Center for Regenerative Medicine will comprise two nodes, one in Stockholm and one in Hong Kong, and will allow scientists from Hong Kong, China, and around the world to work together in an independent research environment under the auspices of Karolinska Institutet. The Center’s research focus will be on three major disease areas in which Karolinska Institutet and several Hong Kong universities possess unique expertise. One of its objectives is to use stem cell technology to rebuild damaged tissue, focusing, for example, on heart tissue damaged by infarction, spinal injury and finding a cure for Parkinson’s disease, and on repairing a damaged liver using stem cell transplants. “This exceedingly generous donation from Ming Wai presents unprecedented opportunities to do groundbreaking research in these extremely important disease areas,” says Professor Anders Hamsten, vice-chancellor of Karolinska Institutet. “The new center will provide our university with a pathway to critically important knowledge and bring us closer to key partners.” The donor Mr. Ming Wai Lau is the Chairman and Chief Executive Officer of Chinese Estates Holdings Ltd and Vice Chairman of the Bauhinia Foundation Research Centre. He holds a Master of Laws and a PhD from the London School of Economics and King’s College London, with his doctoral thesis being published as a book by Oxford University Press in 2011. He is also a registered attorney in the State of New York and in 2014 was a visiting lecturer at Harvard Law School, Boston, USA. Ming Wai Lau is also active in public affairs.   Read more in a press release.  

KI withdraws application for recruitment of top scientist

Fri, 30/01/2015 - 13:13
Karolinska Institutet has withdrawn the application to the Swedish Research Council approved last month for the recruitment of Professor Nils-Göran Larsson from the Max Planck Institute for Biology of Ageing in Cologne, Germany.  The application did not meet the formal requirements, a mistake that the university discovered just before receiving and signing the contract. On 15 January, the Swedish Research Council (VR) decided to grant Karolinska Institutet a total of 100 million kronor to finance the recruitment of Professor Larsson; this sum has now been retracted since KI drew attention to the fact that the formal application requirements had not been met. Since 2007, when Professor Larsson was appointed director of the Max Planck Institute in Cologne, he has been on 80 per cent leave from his duties at KI in accordance with the Max Planck Institute’s regulations for side-line occupations. VR allows temporary employment of up to 20 per cent of full time at KI (as a visiting professor) under the current programme for the international recruitment of outstanding researchers, but not permanent employment (even if the employee is on 80 per cent leave). KI has therefore withdrawn the application in question and regrets having failed to fully heed VR’s regulations at the time of application.  

Investigations into suspected irregularities

Wed, 28/01/2015 - 09:09
Two cases of suspected scientific misconduct involving Paolo Macchiarini, surgeon and visiting researcher at Karolinska Institutet, are now under investigation. In one of the cases, the vice-chancellor has tasked an external expert to issue a statement on the matter, which although expected in mid-February, could be delayed a few weeks given the volume of material. The statement will be passed to the vice chancellor, who will then announce his decision on the matter.  For the second of the two cases involving Professor Macchiarini, the vice-chancellor has requested a pronouncement from Karolinska Institutet’s Ethics Council. This too is expected in February and will also be submitted to the vice-chancellor. The Ethics Council has also been asked by the vice-chancellor to issue a statement on a report against Dr Karl-Henrik Grinnemo, who is affiliated to Karolinska Institutet and who is one of the four doctors behind the allegations against Professor Macchiarini. This third case concerns suspected irregularities relating to a grant application that were reported by a colleague of Professor Macchiarini. The Ethics Council’s statement is expected within the coming few weeks.  The Higher Education Ordinance requires an institute to investigate suspected scientific misconduct should it receive a report of such. According to Karolinska Institutet’s regulations, it is the duty of the vice-chancellor to investigate a report of this kind and decide on it either by passing it on without further action, or, if misconduct is confirmed, by taking appropriate action. Karolinska Institutet does not wish to anticipate the outcome of these investigations and will pass no comment on them until they have been concluded. Some press reports on these cases: New York Times: "Leading Surgeon Is Accused of Misconduct in Experimental Transplant Operations". Nature: "Investigations launched into artificial tracheas".

Swedish scientists show the impact of approved drugs on human proteins

Fri, 23/01/2015 - 10:10
A research article published in Science presents the first major analysis based on the Human Protein Atlas, including a detailed picture of the proteins that are linked to cancer, and the targets for all approved drugs on the market. The Human Protein Atlas, launched in November 2014, is an open source tissue-based interactive map of the human proteome. Based on 13 million annotated images, the database maps the distribution of proteins in all major tissues and organs in the human body. As an open access resource, it is expected to help drive the development of new diagnostics and drugs, but also to provide basic insights in normal human biology. In the newly published Science article, over 90 percent of the approximately 20,000 protein coding genes in humans were analysed. The study shows that some proteins are present in all tissues and others in specific organs such as heart, liver and blood. This information is important for the pharmaceutical industry. The 618 proteins that act as targets of all approved drugs on the market were analysed specifically, and it was shown that 70 percent of these were excreted or in the cell membrane. Present in all tissues The information can be used to explain how different drugs work and why some of them have side effects. For example, the analysis showed that 30 percent of the targets are present in all tissues. This can explain why certain drugs have side effects. The researchers hope that the results of the analysis can be used to develop improved drugs in the future. “It is such a great time to do research", said study co-author Jan Mulder, researcher at the Department of Neuroscience at Karolinska Institutet and affiliated to the national research facility Science for Life Laboratory (SciLifeLab). "By completing the human protein atlas we  are now able to retrospectively look at drug targets and their distribution in normal tissue. The next step would be to utilize this data and other global expression data that is rapidly being generated to find new and better targets for many of the diseases humanity struggles with.” This study was carried out by researchers in Sweden at Royal Institute of Technology (KTH), Uppsala University, Karolinska Institutet, Chalmers University of Technology, Lund University, Stockholm University, and SciLifeLab.  It was funded by the Knut and Alice Wallenberg Foundation.  The research was led by Mattias Uhlén at KTH and SciLifeLab. Learn more about the Human Protein Atlas View a press release from KTH about the findings Publication Tissue-based map of the human proteome Mathias Uhlén, Linn Fagerberg, Björn M Hallström, Cecilia Lindskog, Per Oksvold, Adil Mardinoglu, Åsa Sivertsson, Caroline Kampf, Evelina Sjöstedt, Anna Asplund,  IngMarie Olsson, Karolina Edlund, Emma Lundberg, Sanjay Navani, Cristina Al-Khalili Szigyarto, Jacob Odeberg, Dijana Djureinovic, Jenny Ottosson Takanen, Sophia Hober, Tove Alm, Per-Henrik Edqvist, Holger Berling, Hanna Tegel, Jan Mulder, Johan Rockberg, Peter Nilsson, Jochen M Schwenk, Marica Hamsten, Kalle von Feilitzen, Mattias Forsberg, Lukas Persson, Fredric Johansson, Martin Zwahlen, Gunnar von Heijne, Jens Nielsen, Fredrik Pontén Science, online  23 January 2015, doi: 10.1126/science.1260419

KI receives 100 million for recruitment of top international scientist

Mon, 19/01/2015 - 10:10
The Swedish Research Council (VR) has decided to grant Karolinska Institutet a total of 100 million kronor to finance the recruitment of Professor Nils-Göran Larsson from the Max Planck Institute for Biology of Ageing in Cologne, Germany. The funds will be distributed over a period of ten years. Nils-Göran Larsson has worked at the Department of Laboratory Medicine, Karolinska Institutet for several years. His research concerns mitochondrial function and dysfunction in the healthy and sick, with a particular emphasis on ageing. His work at Karolinska Institutet is expected to contribute to the establishment of strong translational research environments in a clinical setting.  VR has approved three of 44 submitted applications to finance the international recruitment of outstanding researchers. The remaining funds will go to Uppsala and Stockholm universities.

Environment drives human immune variation more than genes

Thu, 15/01/2015 - 18:18
A study of twins conducted by Swedish and American investigators shows that our environment, not our heredity, plays the starring role in determining the state of our immune system, the body’s primary defense against disease. This is especially true as we age, the study indicates. The findings are being published in the journal Cell. Much has been made of the role genes play in human health. Stunning advances in gene-sequencing technologies have caused many scientists to focus to minute variations in the genome, in the hope of predicting people’s future health. Such studies have revealed genetic contributions to health outcomes. But, with some notable exceptions, very few of those individual genetic variants seem to contribute much in particular health conditions. To determine nature’s and nurture’s relative contributions, scientists at Sweden’s Karolinska Institutet and Science for Life Laboratory (SciLifeLab) together with colleagues at Stanford University in the United States turned to a century-old method of teasing apart environmental and hereditary influences: They compared pairs of monozygotic twins — best known to most of us as “identical — and of dizygotic, or fraternal, twins. Monozygotic twins inherit the same genome. Despite inevitable copying errors when cells divide, which cause numerous tiny genetic divergences to accumulate between monozygotic twins over time, they remain almost 100 percent genetically identical. Dizygotic twins are no more alike genetically than regular siblings, on average sharing 50 percent of their genes. Sophisticated laboratory methods Because both types of twins share the same environment in utero and usually share the same environment in childhood, they make excellent subjects for contrasting hereditary versus environmental influence. For the new study, the researchers recruited 78 monozygotic-twin pairs and 27 pairs of dizygotic twins from the registry and then applied sophisticated laboratory methods to participants’ blood samples to measure more than 200 distinct immune-system components and activities. “Examining differences in the levels and activity states of these components within pairs of monozygotic and dizygotic twins, we found that in three-quarters of the measurements, non-heritable influences such as previous microbial or toxic exposures, vaccinations, diet and dental hygiene trumped heritable ones when it came to accounting for differences within a pair of twins”, said lead author Petter Brodin, MD, PhD at SciLifeLab and Karolinska Institutet’s Department of Medicine, Solna. “This environmental dominance became more pronounced when divergences between young identical twins, under the age of 20, were compared to those much older twins, ages 60 and up. Even traits that correlated quite strongly within these pairs in youth often lost that correlation in advanced age.” The research team also observed considerable environmental influence over the quantities of antibodies produced in members of twin pairs who had been vaccinated for influenza. While many previous studies have suggested a powerful genetic component in vaccine responsiveness, Brodin et al noted that those studies typically were performed in very young children who had not yet undergone the decades of environmental exposure that appears to reshape the immune system over time. Chronic carriers of cytomegalovirus In a striking example of the immune system’s plasticity, the study found that the presence or absence of a single chronic, viral infection could have a massive effect on the system’s composition and responsiveness. Three out of five Americans and as many as nine out of 10 people in the developing world are chronic carriers of cytomegalovirus, which is dangerous in immune-comprised people but otherwise generally benign. In 16 of the 27 monozygotic twin pairs participating in the study, one member of the pair had been exposed to cytomegalovirus but the other had not. For nearly 60 percent of all the features measured, cytomegalovirus’s presence in one twin and absence in another made a big difference. “Non-heritable influences, particularly microbes, seem to play a huge role in driving immune variation,” said senior author Mark Davis, PhD, professor of microbiology and director of Stanford’s Institute for Immunity, Transplantation and Infection. “At least for the first 20 or so years of your life, when your immune system is maturing, this amazing system appears able to adapt to wildly different environmental conditions. A healthy human immune system continually adapts to its encounters with hostile pathogens, friendly gut microbes, nutritional components and more, overshadowing the influences of most heritable factors.” The work was funded principally by the National Institutes of Health, the Howard Hughes Medical Institute, the Wenner-Gren Foundation, and the Sweden-America Foundation. More about this study in a press release from Stanford University  Publication Variation in the human immune system is largely driven by non-heritable influences Petter Brodin, Vladimir Jojic, Tianxiang Gao, Sanchita Bhattacharya, Cesar J Lopez Angel, David Furman, Shai Shen-Orr, Cornelia L Dekker, Gary E. Swan, Atul J Butte, Holden T Maecker, Mark M Davis Cell online 15 January 2015

Attempted suicide among young people can be reduced by 50 percent

Fri, 09/01/2015 - 08:08
A new study published in journal The Lancet outlines a programme for preventing suicidality among young people. The results provide strong endorsement for a method whereby school students learn to discover signs of mental ill-health in themselves and their friends, while they are also trained to understand, interpret and manage challenging emotions. The European study was led from Karolinska Institutet, and researchers now hope to see the method reach a large number of young people in European schools. At a global level, suicide is the second leading cause of death in the age group 15-29. Only road traffic accidents cause more fatalities in this age group.  At the same time, there has been a lack of knowledge about which strategy is best for preventing suicidal behaviours in young people. A major EU-funded study which embraces more than 11,000 school students from 168 schools in ten EU countries has therefore evaluated different strategies for prevention of suicidality in young people.  Three methods In the study, schools were randomized to receive one of three suicide prevention models or alternatively become part of a control group. The three methods were: An US method whereby teachers and other school personnel are trained to recognise signs of suicidality and motivate the students to seek help.   A classroom screening test where psychiatrists, psychologists and counsellors identify students with mental health problems and refer them to treatment. The Awareness Programme which was developed by researchers at Karolinska Institutet in Sweden and Columbia University in the USA. It is a method whereby students learn both to recognise signs of mental health problems and cultivate good mental health with short lectures, posters in classroom environments and a more comprehensive brochure to take home. Students were also invited to take part in supervised role-play where they could explore their emotions and learn coping strategies for a variety of difficult life situations that could lead to suicidal behaviours. The educational programme lasted five hours over four weeks. No measures were taken in the control group except for putting up the posters that were part of the Awareness Programme in the classrooms. The study provides results showing the effectiveness of the Awareness Programme – which gives students a tool to exercise influence over their mental health – in preventing attempted suicide and serious suicidal thoughts with plans how to commit suicide. One year after completing the programme, the number of attempted suicides and serious suicidal thoughts and planned suicides in this group was 50% lower compared with the control group. Professional health care personnel In the two other groups, where the responsibility for the students’ mental health rested exclusively with the teacher or professional health care personnel, the proportion was the same as in the control group. “This study provides much-needed evidence for the effectiveness of universal school-based public health programmes designed for students. The study shows that it possible to implement suicide prevention programmes in schools with good results. Now we can take the step from following statistics that indicate the seriousness of the problem, towards actively and comprehensively using the Awareness Programme in schools. We also plan to develop the method into a modern web-based solution such as a mobile phone app to reach as many young people as possible,” said Danuta Wasserman, Professor at the Department of Learning, Informatics, Management and Ethics, and head of the National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP) at Karolinska Institutet, Sweden. The study was funded by an EU grant from the Seventh Framework Programme (FP7). It is led from NASP, which also is WHO’s collaborative partner in the field.  View a press release about this research Publication A Randomised Controlled Trial of School-based Suicide Preventive Programmes; The Saving and Empowering Young Lives in Europe Study (SEYLE) Danuta Wasserman, Christina W Hoven, Camilla Wasserman, Melanie Wall, Ruth Eisenberg, Gergö Hadlaczky, Ian Kelleher, Marco Sarchiapone, Alan Apter, Judit Balazs, Julio Bobes, Romuald Brunner, Paul Corcoran, Doina Cosman, Francis Guillemin, Christian Haring, Miriam Iosue, Michael Kaess, Jean-Pierre Kahn, Helen Keeley, George Musa, Bogdan Nemes, Vita Postuvan, Pilar Saiz, Stella Reiter-Theil, Airi Varnik, Peeter Varnik & Vladimir Carli The Lancet, online 9 January 2015

Urban Lendahl new Secretary for the Nobel Prize in Physiology or Medicine

Fri, 19/12/2014 - 15:15
Professor Urban Lendahl has been elected as the new Secretary of the Nobel Assembly at Karolinska Institutet and Nobel Committee for Physiology or Medicine. Lendahl succeeds Professor Göran Hansson, who has been has been elected Permanent Secretary of the Royal Swedish Academy of Sciences. Lendahl will take office starting January 1, 2015.  Professor Lendahl is Professor of Genetics at the Department of Cell- and Molecular Biology, Karolinska Institutet. He was a member of the Nobel Committee for Physiology or Medicine 2007-2013 and Chairman of the Nobel Committee 2012. He has been a member of the Nobel Assembly since July 1, 2000.The present Secretary, Professor Göran Hansson, has been elected Permanent Secretary of the Royal Swedish Academy of Sciences and will take up this position on July 1, 2015. Professor Hansson remains a member of the Nobel Assembly. - Urban Lendahl has high integrity and is extremely well respected amongst his colleagues. I am delighted to have this opportunity to work together with Professor Lendahl as he takes on this important task. It has been a pleasure to work together with Professor Hansson and I look forward to further interactions in his role as Permanent Secretary of the Royal Swedish Academy of Sciences and Member of the Nobel Assembly, says Professor Juleen R. Zierath, Chairman of the Nobel Committee at Karolinska Institutet.

Endogenous retroviruses important in immune response

Fri, 19/12/2014 - 09:09
A new study in Science, in which researchers from Karolinska Institutet participated, shows that retroviruses may not only be harmful to humans. According the findings, so called endogenous retroviruses, which are included in the genome of each person, could play an important role in the body’s immune defense against common bacterial and viral pathogens. Retroviruses are best known for causing contagious scourges, such as AIDS or cancer. They are able to insert into the genomic DNA of cells that they infect, including germ cells. Millions of years ago, retroviruses were included in the human genome through a process called retrotransposition. About 45 percent of a person’s DNA is of retroviral origin, and some of the better preserved copies are termed endogenous retroviruses (ERV).  These genetic elements do not cause infection, and it has been unclear if they have any function at all. Writing in the journal Science, researchers at UT Southwestern Medical Center and Karolinska Institutet have found that when B cells are activated by large polymeric antigens such as polysaccharides of bacteria, they rapidly produce protective antibodies in what is termed the type II T-independent antibody response. This response, central to the body’s defense against common bacterial and viral pathogens, is dependent on ERV.  “We believe that, once retroviruses have become part of the host germline, they are subject to selection for beneficial effects just like any other part of the genome, and their ability to activate an innate immune response seems to have been utilized to the benefit of the host,” says Dr. Gunilla Karlsson Hedestam, Professor at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. Reverse transcriptase The research team shows that within activated B cells the ERV are driven to express RNA copies of themselves, which in turn are copied into DNA by an enzyme called reverse transcriptase. The RNA copies of endogenous retroviruses are detected by a protein called RIG-I, and the DNA copies are detected by another protein called cGAS.  These two proteins send further signals that enable the B cells to sustain their activated state, proliferate, and produce antibodies. “Mice lacking elements of the RIG-I or cGAS pathways show diminished responses to type II T-independent antigens, and mice lacking both pathways show almost no antibody response at all to these antigens. Moreover, reverse transcriptase inhibiting drugs also partially inhibit the type II T-independent antibody response”, observes Gunilla Karlsson Hedestam. Principal investigator of this current study has been Dr. Bruce Beutler, Professor and Director of UT Southwestern Center for the Genetics of Host Defense, who shared the 2011 Nobel Prize in Physiology or Medicine. The work was funded by donations from the Lyda Hill Foundation and the Kent and JoAnn Foster Family Foundation, and by NIH grants. View a commentary in Science about the findings View a press release from UT Southwestern Medical Center Publication MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses Ming Zeng, Zeping Hu, Xiaolei Shi, Xiaohong Li, Xiaoming Zhan, Xiao-Dong Li, JianhuiWang, Jin Huk Choi, Kwan-wenWang, Tiana Purrington, Miao Tang, Maggy Fina, Ralph J. De Berardinis, Eva Marie Y. Moresco, Gabriel Pedersen, Gerald M. McInerney, Gunilla B. Karlsson Hedestam, Zhijian J. Chen, Bruce Beutler Science online 18 December 2014, doi: 10.1126/science.1257780

Physical activity improves survival for men with localized prostate cancer

Fri, 19/12/2014 - 09:09
A new study from Karolinska Institutet shows that men with localized prostate cancer who engaged in higher levels of physical activity had lower rates of overall mortality and lower rates of prostate cancer-specific mortality, compared with less active counterparts. The findings are being published in the journal Cancer Epidemiology, Biomarkers & Prevention. Researchers analyzed data from 4,623 men in the National Prostate Cancer Register of Sweden Follow-up Study, who were diagnosed with localized prostate cancer from 1997 to 2002 and followed until 2012. Data on physical activity was obtained through paper- and web-based questionnaires about lifestyle. Information about cause and date of death were obtained from the Swedish Cause-of-Death Registry. The results show that men with localized prostate cancer who walked or cycled for 20 or more minutes a day had a 30 percent decreased risk of death from any cause (overall mortality) and a 39 percent decreased risk of death as a result of their disease (prostate cancer-specific mortality) compared with those who walked or cycled less. For those who engaged in 1 or more hours of exercise per week, overall and prostate cancer-specific mortality rates were decreased by 26 percent and 32 percent, respectively, compared with less active counterparts. “Our results extend the known benefits of physical activity to include prostate cancer-specific survival,” says Stephanie Bonn, MSc, a doctoral student at the Department of Medical Epidemiology and Biostatistics. “However, it is important to remember that our results are based on group level. An individual’s survival depends on many factors, but physical activity is one factor that individuals can modify. Hopefully, our study can motivate men to be physically active even after a prostate cancer diagnosis.” The study was supported by the Swedish Cancer Society, and the Swedish Research Council for Health, Working life and Welfare, and it was headed by Katarina Bälter, PhD, Senior lecturer at the Department of Medical Epidemiology and Biostatistics. Publication Physical activity and survival among men diagnosed with prostate cancer Stephanie E Bonn, Arvid Sjölander, Ylva Trolle Lagerros, Fredrik Wiklund, Pär Stattin, Erik Holmberg, Henrik Grönberg, Katarina Bälter Cancer Epidemiology, Biomarkers & Prevention, online 19 December 2014

Website statistics can predict emergency room visit volumes

Mon, 15/12/2014 - 13:13
A new study from Karolinska Institutet and Södersjukhuset suggests that statistics on website visits may be used to predict the level of demand at emergency departments. The study, which is being published in the journal Annals of Emergency Medicine, shows a significant correlation between Internet searches on a regional medical website and next-day visits to regional emergency departments. Using Google Analytics, researchers tallied and graphed Internet searches of the Stockholm Health Care Guide (SHCG), a regional medical website, over a one-year period and compared them to emergency department visits over the same period. Visits to the SHCG between the hours of 6:00 p.m. and midnight were significantly correlated to the number of emergency room visits the next day.  The most accurate forecasting for emergency department visits was achieved for the entire county, with an error rate of 4.8 percent.  The error rate of forecasting individual hospitals’ emergency department visit rates based on Internet searches ranged from 5.2 percent to 13.1 percent.  (An error rate below 10 percent was considered good performance, as this is on par with other methods already described for forecasting emergency room visit volumes.) The research team behind the finding, conclude that website analytics may be used to predict emergency room visits for a geographic region, as well as for individual hospitals. Looking forward, researchers also suggest that it might be possible to create a model to predict emergency department visits that would enable better matching of personnel scheduling to emergency room volumes. All co-authors are affiliated to Karolinska Institutet’s Department of Clinical Science and Education, Södersjukhuset (Stockholm South General Hospital). Annals of Emergency Medicine is the peer-reviewed scientific journal for the American College of Emergency Physicians. View a press release from the American College of Emergency Physicians Publikation Forecasting Emergency Department Visits Using Internet Data Andreas Ekström, Lisa Kurland, Nasim Farrokhnia, Maaret Castrén & Martin Nordberg Annals of Emergency Medicine, published online as corrected proof on December 4th, 2014, doi: http://dx.doi.org/10.1016/j.annemergmed.2014.10.008

Swede of the Year Johan von Schreeb started the Ebola training course

Thu, 11/12/2014 - 13:13
The Ebola outbreak will get out of hand in early December if attempts to combat the disease do not intensify, predicted the UN in mid-October. Since then, the government has ring-fenced half a billion kronor to stop the spread of the disease, and Karolinska Institutet has trained some 100 individuals to work in the affected areas. The course was instigated by Johan von Schreeb, surgeon and docent at KI’s Centre for Disaster Medicine and recipient of Focus magazine’s Swede of the Year title. The course was created as a direct result of the acute lack of healthcare workers in West Africa. It is two days long and involves several experts. Earlier this autumn, Johan von Schreeb returned home from Sierra Leone, where he was working for the World Health Organisation. To him, like other experts in the area, it is clear that the Ebola crisis can not be solved by money alone. “We can’t rely on organisations like Doctors without Borders to handle the situation on their own and must send Swedish medical personnel down,” says Dr von Schreeb. “Ebola training for fieldworkers” was put together in just over a week, which probably makes it the most hastily organised course in KI’s history. As late as just a few days before the scheduled start on 13 October, a training centre was being set up in accordance with specifications issued by Doctors without Borders for how an Ebola treatment centre (ETC) is to be organised for the care of patients with a suspected or confirmed infection. The physical location of the training camp is the old gymnastics hall on the KI campus. The course focuses on handling the influx of patients into the camp and on training important things like handling samples and putting on and taking off protective clothing, including rubber boots, double gloves, breathing mask and visor. Another important aspect is prioritising the patients. It is essential to preventing the spread of Ebola that only infected people are brought into the ETC. Nurse Anneli Eriksson, who is leading the course with Dr von Schreeb, has a great deal of experience working and training personnel in the field. Earlier this autumn she returned home from one of Doctors without Borders’s largest camps in Liberia.   “The safety of medical staff is top priority, but we need to prepare ourselves if we’re to work in a way that doesn’t expose us to danger,” says Ms Eriksson. Even though her camp was the organisation’s largest, the staff still had to turn away some of the sick. The principle there is effectively “one corpse out, one patient in”. The training also includes the handling of dead bodies and safe burials. Originally, the idea was for KI to hold three courses and then evaluate them. But at the start of November, an additional course was quickly arranged to meet the need for more trained medics in Liberia. Despite the short notice, the course was over-subscribed and the majority of its participants are already booked to travel. Drumming up interest in the course is thus no problem. If the shoe pinches anywhere, it is with the employers. “If Swedish medical staff are to go to Africa and help, they must be released by their managers in the healthcare services, which isn’t always the case,” says Dr von Schreeb. The training is organised by the Centre for Excellence for Disaster Medicine at KI in association with the National Board of Health and Welfare, Doctors without Borders, the Public Health Agency of Sweden, and the Swedish Civil Contingencies Agency (MSB).   Text: Jenny Ryltenius   How Ebola spreads: Ebola is caused by a virus and is a type of viral hemorrhagic fever. It is passed on through direct contact with infected bodily fluids, such as vomit, saliva, blood, coughs and sneezes, and with infected dead bodies. Infection is most likely to occur during the care and handling of the sick, so those at greatest risk are family members and medical personnel. Source: The Public Health Agency of Sweden and Doctors without Borders. "I'm deeply honoured", says Johan von Schreeb in the Focus magazine. Read the full article (in Swedish only).      

Hexagonal patterns in Aula Medica foyer celebrate Nobel lectures

Tue, 09/12/2014 - 09:09
The 2014 Nobel laureates in Physiology or Medicine, John O'Keefe, May-Britt Moser and Edvard Moser, provided a mix of data old and new as well as a good few laughs at the Nobel lectures in the Karolinska Institutet auditorium on Sunday 7 December. By eleven when Aula Medica opened, some people had already been waiting outside for an hour so as not to miss the Nobel lectures, which began two hours later. If it had not been for the red candles and a Christmas tree in the entrance, one might have forgotten it was December, given the bright sunshine and above-zero temperatures. After more queuing indoors, where posters of the Nobel-winning discovery of the brain’s own GPS system were quickly snapped up, the members of the audience were finally able to find their places in the auditorium itself. On welcoming everyone to the lectures, Karolinska Institutet’s vice-chancellor, Professor Anders Hamsten, handed over to Professor Hans Forssberg to introduce the three laureates. First up was Professor John O’Keefe, who quoted a poem that he and a colleague wrote back in 1978: “Space plays a role in all our behaviour. We live in it, move through it, explore it, defend it”. His research was about the cells that make up a positioning system in the brain: the hippocampal place cells that he himself discovered, plus other cells like the grid cells in the entorhinal cortex, that the Mosers discovered. His lecture included data suggesting that part of the positioning system appears in neonate rats even before they have had any real sensory input from their surroundings. He also described a water maze for laboratory animals invented by a colleague to test one of his early hypotheses. “This water maze is still the most popular and most potent test of hippocampal function available today,” he said. Professor Edvard Moser was next, and lectured on the hexagonal patterns that the grid cells create in the brain, adding that they are also present in other, different contexts, such as the windows of Aula Medica. “I suspect that the Nobel Committee has been planning this day for a long time,” he said, raising a chuckle from the audience, some of whom perhaps noted afterwards that it wasn’t only the exterior of the auditorium that had a hexagonal pattern, but also the floor of the foyer and the paving outside. Professor May-Britt Moser began her lecture with a short film that also raised a peal of laughter from the audience. It was of a mouse trying to carry a biscuit up onto a platform, which she compared to a scientist trying to solve scientific problem. After many failed attempts, the mouse finally succeeded. “Science is a field where the impossible can become possible,” she said. She then went on to talk about how the grid cells and other cells influence the place cells, about cells in the entorhinal cortex that detect speed, and about how smells can be associated with locations. Edvard Moser and May-Britt Moser both spent some time at John O’Keefe’s lab at the start of their careers. “It was the most efficient learning period of my life,” said Edvard Moser during his lecture. It is the kind of interaction that the Mosers and John O’Keefe are still engaged in to this day. During the post-lecture reception May-Britt Moser mentioned that next year John O’Keefe will be at Norway’s Teknisk‐Naturvitenskapelige Universitet in Trondheim, where the Mosers work, as a visiting professor. And Edvard Moser said that the three of them have together invited 160 guests to a joint party in the Nobel Forum later that evening. “This is a research field in which everyone knows each other really well, and we wanted to invite all those people who have done their bit for science,” he said. “But of course we couldn’t invite everyone to the Nobel party.”   Text: Lisa Reimegård Photo: Erik Cronberg     Watch the lectures on YouTube:

Long-term endurance training impacts muscle epigenetics

Tue, 09/12/2014 - 08:08
A new study from Karolinska Institutet in Sweden shows that long-term endurance training in a stable way alters the epigenetic pattern in the human skeletal muscle. The research team behind the study, which is being published in the journal Epigenetics, also found strong links between these altered epigenetic patterns and the activity in genes controlling improved metabolism and inflammation. The results may have future implications for prevention and treatment of heart disease, diabetes and obesity. “It is well-established that being inactive is perilous, and that regular physical activity improves health, quality of life and life expectancy”, says Professor Carl Johan Sundberg, Principal Investigator at the Department of Physiology and Pharmacology. “However, exactly how the positive effects of training are induced in the body has been unclear. This study indicates that epigenetics is an important part in skeletal muscle adaptation to endurance training.” Epigenetics can simply be described as temporary biochemical changes in the genome, caused by various forms of environmental impact. One type of epigenetic change is methylation, where a methyl group is added to or removed from a base in the DNA molecule without affecting the original DNA sequence. If genes are considered the hardware of cells, then epigenetics can be seen as their software. One-legged cycling The current study included 23 young and healthy men and women who performed supervised one-legged cycling, where the untrained leg served as a control. The volunteers participated in 45 minutes training sessions four times per week during a three month period. Performance was measured in both legs before and after training. In the skeletal muscle biopsies, markers for skeletal muscle metabolism, methylation status of 480 000 sites in the genome, and activity of over 20 000 genes were measured.  Results show that there were strong associations between epigenetic methylation and the change in activity of 4000 genes in total. Genes associated to genomic regions in which methylation levels increased, were involved in skeletal muscle adaptation and carbohydrate metabolism, while a decreasing degree of methylation occurred in regions associated to inflammation. Important novel finding An interesting and potentially very important novel finding was that a majority of the epigenetic changes occurred in regulatory regions of our genome, so called enhancers. These sequences in our DNA are often situated far away from the actual genes they regulate, in comparison to so called promoter regions, which traditionally have been considered to control most of the gene activity. “We found that endurance training in a coordinated fashion affects thousands of DNA methylation sites and genes associated to improvement in muscle function and health”, says Carl Johan Sundberg. “This could be of great importance for the understanding and treatment of many common diseases such as diabetes and cardiovascular disease, but also for how to maintain a good muscle function throughout life. Interestingly, we also saw that there were epigenetic differences between male and female skeletal muscle, which may be of importance to develop gender specific therapies in the future.” First study-authors are Maléne Lindholm and Francesco Marabita, both at Karolinska Institutet. The study has been funded by grants from the Swedish National Centre for Research in Sports, Torsten Söderberg Foundation, the STATegra network within the EU’s FP7, Stockholm County Council, and the Swedish Research Council. View a press release about this research Publication  An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training Maléne E Lindholm, Francesco Marabita, David Gomez-Cabrero, Helene Rundqvist, Tomas J Ekström, Jesper Tegnér & Carl Johan Sundberg Epigenetics, first online 7th December 2014, doi:10.4161/15592294.2014.982445

The election is over – at least for KI

Fri, 05/12/2014 - 13:13
The academic election year at Karolinska Institutet, during which deans, assistant deans and faculty representatives were voted onto the University Board and the three internal boards, drew to a close on 3 December. The deans and assistant deans were elected back in the spring, and on 3 December the identities were established of the faculty members who will be sitting on the boards that the deans will be heading. This means that the boards of Higher Education, Doctoral Education and Research are now ready to set to work for their new term of office that will last from 1 January to 31 December 2017. Earlier in the autumn it was also announced who will be representing the teachers on Karolinska Institutet’s highest executive body, the University Board, from the new year. Elias Arnér will be continuing for another three years, joined by new members Anna Karlsson and Lena Von Koch. All three were elected by KI’s teachers with voting rights in September by means of electronic ballot. The faculty representatives on the internal boards were elected in turn by a nomination assembly comprising 67 departmental representatives. The election of the deans last spring was decided after a consultative election by teachers with voting rights at Karolinska Institutet, whereupon the final decision was taken by Vice-Chancellor Anders Hamsten.  

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