Integrative Molecular Phenotyping

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Updated: 2 hours 9 min ago

The Grand Silver Medal 2015 is awarded to Gunnel Biberfeld, Britta Wahren and SGO Johansson

Thu, 17/09/2015 - 10:10
The Grand Silver Medal 2015 from Karolinska Institutet is awarded to Gunnel Biberfeld, Britta Wahren and SGO Johansson in special recognition of the outstanding contributions they have made to medical research and Karolinska Institutet. The medals will be presented at the installation ceremony on 15 October 2015. The medal committee's citations for Karolinska Institutet's Grand Silver Medals in 2015 are as follows: Gunnel Biberfeld, professor emerita of infectious disease control, especially clinical immunology, is awarded the Grand Silver Medal for her outstanding contribution to research and doctoral education in the area of HIV at Karolinska Institutet. She is one of the pioneers in HIV research, at KI and globally. At a very early stage, she realised the urgent need for research on HIV, and since the beginning of the HIV pandemic she has remained active in this area of research. She has fostered a generation of young HIV researchers at Karolinska Institutet, of which many are now leaders in the field. Gunnel Biberfeld's research into HIV focuses on a global perspective, especially considering her clinical vaccine studies in Tanzania. The research collaboration with Tanzania also includes a comprehensive doctoral program. In addition, Gunnel Biberfeld's studies on the prevention of HIV transmission from mother to child in Dar es Salaam, shows the importance of using antiretroviral therapy during both pregnancy and the postnatal period. The results of these studies have formed the basis for Tanzania's national guidelines for the prevention of HIV transmission from mother to child, and they have also contributed to WHO's recommendations in the area. Britta Wahren, professor emerita of clinical virology, is awarded the Grand Silver Medal for her outstanding contribution to research and doctoral education in the area of HIV and cancer research at Karolinska Institutet. Britta Wahren is one of the pioneers in HIV research and particularly in designing HIV vaccines, at KI and globally. At a very early stage, she realised the urgent need for research on immune responses and protection against HIV. She has fostered a generation of young researchers at Karolinska Institutet, of which many are now leaders in the field. Britta Wahren was the first person in the world to show that a genetic vaccine that expresses early genes/antigens of HIV could induce new cell mediated responses to HIV in already infected individuals. These finding were taken forward to perform experimental and clinical HIV vaccine studies against the many types of HIV that prevail in the world. She designed novel genetic HIV vaccines that induce cell-mediated and humoral immunity of prolonged nature in healthy individuals. Together with the National Institutes of Health and the US Army, a new prime-boost vaccine schedule has been proposed for prophylactic vaccination against HIV. Britta Wahren´s focus has been on translational research, from molecular studies of HIV, tumour viral immunogens and immune responses to the development of novel vaccine prototypes to HIV. S Gunnar O Johansson, professor emeritus of clinical immunology, especially allergology, is awarded the Grand Silver Medal for his outstanding contribution to the area of allergy research. He identified, in 1967, together with Hans Bennisch, a new class of immunoglobulins, IgE, and showed that these are associated with allergic responses. He has established and grown the research area of allergy at Karolinska Institutet, and his successful research has contributed to making Karolinska Institutet into a world leader in the area. SGO Johansson’s groundbreaking discovery of IgE and the development of allergy tests have improved the health and quality of life for a large proportion of the worldwide population. Previous winners

Type 2 diabetic patients should be prioritised for obesity surgery

Thu, 17/09/2015 - 09:09
A new Swedish study suggests that when considering overall costs of healthcare, obese patients with type 2 diabetes should be prioritised for obesity surgery over those who do not suffer from this disease. Many patients see a reversal of diabetes after surgery, and therefor do not need expensive diabetes medications or treatment for future complications.  The findings are being published in the journal The Lancet Diabetes & Endocrinology. The research is based on the Swedish Obese Subjects (SOS) study from Sahlgrenska Academy in Gothenburg and performed in collaboration with Dr Martin Neovius, Karolinska Institutet, Dr Lena Carlsson, Chief SOS Investigator, University of Gothenburg, and Dr Catherine Keating, Deakin University and Baker IDI Heart and Diabetes Institute, Melbourne, Australia. Currently most healthcare systems prioritise access to obesity surgery based on a person’s body-mass index (BMI), and in general, those with the highest BMI are prioritised. Patients with lower BMIs and comorbidities such as type 2 diabetes can also be considered eligible for surgery, but different countries have different guidelines. Several groups have recommended that a person’s diabetes status (rather than BMI alone), be used to prioritise obese patients to receive bariatric surgery. But so far, the long-term effect of bariatric surgery (relative to conventional therapy) on healthcare costs in obese patients according to their diabetes status has not been assessed using real-world data. Accumulated drug costs The data used from the SOS study included 2010 adults who underwent obesity surgery and 2037 matched controls recruited between 1987 and 2001. The analysis showed that accumulated drug costs over 15 years did not differ between the surgery and control group in patients without diabetes at the time of surgery, but were lower in surgery patients who had prediabetes (on average, -US$3329 per patient) or diabetes (-$5487 per patient). However, hospital costs were higher in all patients who had surgery.  No differences in outpatient costs were observed.  Compared with patients treated conventionally, total healthcare costs (accounting for costs of surgery, inpatient and outpatient hospital care and prescription drugs) were higher in surgery patients who did not have diabetes at the beginning of the study (by $22,390 per patient) or who had prediabetes ($26,292), but not in patients with diabetes, most likely because the remission of diabetes that often occurs after bariatric surgery means that patients need fewer diabetes medications and hospital appointments in the subsequent years. Remission of diabetes also means that diabetes complications are lessened, further reducing future healthcare costs. The study was funded by AFA Försäkring, the Swedish Research Council, and Diabetesfonden, amongst others. This news article is an edited version of a press release from The Lancet Diabetes & Endocrinology. Publication Health-care costs over 15 years after bariatric surgery for patients with different baselina glucose statuses: results from the Swedish Obese Subjects study Catherine Keating, Martin Neovius, Kajsa Sjöholm, Markku Peltonen, Kristina Narbro, Jonas K. Eriksson, Lars Sjöström, Lena M.S. Carlsson Lancet Diabetes & Endocrinology online 17 September 2015, S2213-8587(15)00290-9. 

Study explores association between SSRI use and violent crime

Tue, 15/09/2015 - 20:20
The use of antidepressant SSRIs is modestly associated with violent crime in adolescents and young adults, according to a new study published in the journal PLOS Medicine. The cohort study by researchers from Karolinska Institutet and the University of Oxford showed in subgroup analysis that this association was evident in participants aged 15-24, but not significant for individuals aged 25 and older. Selective serotonin reuptake inhibitors (SSRI) are widely prescribed, and effectively used to treat for example depression and anxiety syndrome. Inconclusive evidence, however, links SSRI use with violent behaviour. In the current study, Dr Seena Fazel of Oxford University and colleagues compared the rate of violent crime while individuals were prescribed SSRIs with the rate of violent crime in the same individuals while not receiving medication, using matched data from the Swedish Prescribed Drug Register and the Swedish national crime register. During the 4-year study period (2006-2009), about 850,000 individuals were prescribed SSRIs, and 1% of these individuals were convicted of a violent crime. In age-stratified analysis, associations between SSRI use and convictions for violent crimes were significant for individuals aged 15 to 24 years but not for older individuals. Increased risks were also found in individuals aged 15-24 years for violent arrests, non-violent convictions and arrests, non-fatal accidental injuries and emergency contacts for alcohol-related problems. Do not prove causation According to the study-authors, these findings do not prove causation, as possible time-varying confounding by one or more unidentified factors linked to both SSRI use and violent crime may explain the results. Any change to the advice given to young persons prescribed with SSRIs will need to be carefully considered, and should not be based on one study alone. Lead study-author was Dr Yasmina Molero Samuelson at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. The research has been funded with grants from the Wellcome Trust, Karolinska Institutet, and the Swedish Research Council. This news article is an edited version of a press release from PLOS Medicine. Publication Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study Yasmina Molero, Paul Lichtenstein, Johan Zetterqvist, Clara Hellner Gumpert, Seena Fazel PLoS Med 12(9): e1001875, online 15 September 2015, doi:10.1371/journal.pmed.1001875

KI ranked number nine in the world in QS Faculty Ranking

Tue, 15/09/2015 - 12:12
KI is number nine in the world in the Faculty Ranking Life Sciences and Medicine in the 2015 QS World University Rankings. Each year, QS presents an universal university ranking, as well as so called faculty rankings in different areas. The universal ranking only includes multi-faculty universities and KI is thus not featured in the universal ranking. In the Faculty Ranking Life Sciences and Medicine, KI is ranked number nine in the world and number three in Europe. Last year, KI was number eight in the world. The highest ranked university on the "Sciences and Medicine" list is Harvard University. The universal ranking list is topped by the same university as last year, MIT. Sweden is represented in the top100 by KTH and Lund University. Six months after the universal ranking, QS publishes area-specific rankings. In the area-specific rankings that were announced in March 2015 KI is ranked nine in "Medicine" and six in "Pharmacy&Pharmacology". KI tops the recently introduced ranking list in "Dentistry", in which Gothenburg University and Malmö University also ranked high. The QS rankings have been criticised for statistical uncertainty due to small subject areas, and lack of use of field-normalised bibliometry indicators. Starting with the 2015 ranking, QS uses field-normalised bibliometry data.  Read more at

Kerstin Tham leaves KI to lead Malmö University

Thu, 10/09/2015 - 15:15
The government decided today to appoint Professor Kerstin Tham, pro-vice-chancellor at KI, as vice-chancellor of Malmö University commencing 1 November 2015. Kerstin Tham has been professor of occupational therapy at the Department of Neurobiology, Care Science and Society since 2009 and the pro-vice-chancellor of Karolinska Institutet Since January 2013. Last May, the nomination committee at Malmö University decided to present Kerstin Tham as the only candidate for the post. She had also been selected for recommendation by the consultative assembly and union representatives out of the three shortlisted names. This means that Professor Tham will be vacating the office of pro-vice-chancellor at KI after over two and a half years, and that a replacement must now be found. The post of vice-chancellor at Malmö will last until 31 July 2021. Her predecessor at Malmö University, Stefan Bengtsson, left on August to become president and CEO of Chalmers in Gothenburg. For more on the recruitment of the new pro-vice-chancellor, see

Low resting heart rate associated with increased violent criminality

Thu, 10/09/2015 - 10:10
A low resting heart rate in late adolescence is associated with increased risk for violent criminality in men later in life, according to a new study by researchers at Karolinska Institutet and University of Helsinki, Finland. The findings are being published online in the journal JAMA Psychiatry. Low resting heart rate (RHR) has been viewed either as an indicator of a chronically low level of psychological arousal, which may lead some people to seek stimulating experiences, or as a marker of weakened responses to aversive and stressful stimuli, which can lead to fearless behaviour and risk taking. However, not much is known about RHR as a predictor of severe violence. A better understanding of individual-level biological risk factors in the cause of violence could help prevention and intervention efforts. In the current study, the research team examined the association of RHR in late adolescence to predict violent criminality later in life using data on 710,264 Swedish men born from 1958 to 1991 with up to 35.7 years of follow-up. RHR and blood pressure were measured at mandatory military conscription testing when the men were an average age of 18 years old. There were 40,093 men convicted of a violent crime during nearly 12.9 million person-years of follow-up. Beats per minute The researchers found that compared with 139,511 men with the highest RHR (greater than or equal to 83 beats per minute), the 132, 595 men with the lowest RHR (less than or equal to 60 beats per minute) had a 39 percent higher chance of being convicted of violent crimes and a 25 percent higher chance of being convicted of nonviolent crimes when the analysis models accounted for an assortment of variables. The study was supervised by Drs Paul Lichtenstein and Henrik Larsson at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, and funded with grants from the Swedish Research Council for Health, Working Life and Welfare, the Swedish Research Council, the Academy of Finland, the Alfred Kordelin Foundation, and the European Union Seventh Framework Programme. This news article is and edited version of a press release from JAMA Network. Publication A Longitudinal Study of Resting Heart Rate and Violent Criminality in More Than 700 000 Men Antti Latvala,  Ralf Kuja-Halkola,  Catarina Almqvist,  Henrik Larsson, Paul Lichtenstein,  JAMA Psychiatry, published online September 09, 2015. doi:10.1001/jamapsychiatry.2015.1165

Smoking associated with accelerated disease progression in MS

Wed, 09/09/2015 - 08:08
Continued smoking after a diagnosis of multiple sclerosis (MS) appears to be associated with accelerated disease progression compared with those patients who quit smoking, according to a new study by researchers from Karolinska Institutet. The findings are being published online in JAMA Neurology. “There are of course a number of health risks connected to smoking, but for people diagnosed with a such a severe disease as MS, it is especially important to quit smoking immediately”, says study leader Jan Hillert, MD, PhD, Professor of Neurology at Karolinska Institutet’s Department of Clinical Neuroscience. MS is a neurogenerative disease and smoking is one of its known risk factors. While MS begins with an initial course of irregular and worsening relapses, it usually changes after about 20 years into secondary progressive (SP) disease. The time that passes from onset to conversion to SPMS is a frequently used measure of disease progression. The current study included 728 patients in Sweden with MS who smoked at diagnosis, of whom 216 converted to SP. Among the smokers, 332 were classified as 'continuers' who smoked continuously from the year after diagnosis, and 118 were 'quitters' who stopped smoking the year after diagnosis. Data on 1,012 never smokers also were included. Nearly 60 percent of patients with MS were smokers in the present study cohort and in a Swedish cohort of new cases, according to study background. Each additional year Analysis by the authors suggests each additional year of smoking after diagnosis accelerated the time to SP conversion by 4.7 percent. Other analysis suggested that those patients who continued to smoke each year after diagnosis converted to SP faster (at age 48) than those who quit (at age 56). Funding this study was provided by Neuroförbundet, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the AFA foundation, the Swedish Brain Foundation, Margareta af Ugglas Stiftelse, EU FP7 Neurinox, the Bibby and Nils Jensen Foundation, and the Karolinska Institutet Research fund. This news article is an edited version of a press release from JAMA Network. Publication Effect of Smoking Cessation on Multiple Sclerosis Prognosis Ryan Ramanujam, Anna-Karin Hedström, Ali Manouchehrinia, Lars Alfredsson, Tomas Olsson, Matteo Bottai, Jan Hillert JAMA Neurology, doi:10.1001/jamaneurol.2015.1788, online September 8, 2015

Emma Andersson and Robert Månsson is to be awarded the 2014 Hagberg prize

Tue, 08/09/2015 - 15:15
The Sven and Ebba-Christina Hagberg prize in medicine 2014 is awarded to Emma Andersson, Senior researcher at the Department of Biosciences and Robert Månsson, Assistant professor at the Department of Laboratory Medicine. Emma Andersson is awarded the prize for her work concerning how the Wnt and Notch signalling pathways control differentiation and morphogenesis during embryonic development. It is important to gain an understanding of these signalling pathways, since a range of diseases can arise when they do not function properly during development. Dr Andersson is doing important research into Alagille syndrome, a genetic disorder that arises in early childhood and affects the liver, heart and kidney.  Robert Månsson is awarded the prize for his work concerning early haematopoiesis and three-dimensional genomic architecture, and the relationship between this higher order genomic organization of genes and transcriptional regulation. He is particularly interested in genes that are involved in the development of blood cells. The overall aim of his work is to gain a greater understanding of normal blood cell development why some genetic mutations cause blood cancers. About the prize: The Sven and Ebba-Christina Hagberg Prize awards a personal prize and research funding to especially outstanding junior researchers at Karolinska Institutet. This year, the prizewinners will be awarded SEK 150,000 each as well as research funding to the sum of SEK 175,000 each. The prize will be awarded at Karolinska Institutet’s Installation Ceremony on 15 October 2015.

New molecular test can reveal biological age

Tue, 08/09/2015 - 09:09
A new molecular test, which can indicate the unique rate at which a person is ageing, could transform the way ageing is approached in medical research by assessing a person’s ‘biological age’ rather than the number of years one has lived. The findings, published the journal Genome Biology, could help manage age-related disease by identifying people most at risk of diseases affected by age, as well as improve the way anti-ageing treatments are evaluated. The seven-year collaborative study at King’s College London, Karolinska Institutet and Uppsala University in Sweden, and Duke University in the USA, used a process called RNA-profiling to measure and compare gene expression in thousands of human tissue samples. Rather than look for genes associated with disease or extreme longevity, the researchers discovered that the ‘activation’ of 150 genes in the blood, brain and muscle tissue were a hallmark of good health at 65 years of age. After discovering that it was the levels of the exact same genes that were regulated in very different types of tissue, the researchers were able to create a formula for ‘healthy ageing’, and use this test to tell how well a person is ageing when compared to others born the same year. The extensive range in ‘biological age’ scores of people born at the same time indicates that a person’s biological age is separate and distinct to his/her chronological age. Lower cognitive status Importantly, a low score was found to reflect lower cognitive status, with low levels of gene expression measured in the blood also reflecting regulation of the same genes in brain regions involved with neurodegeneration. These findings imply that the molecular test could translate into a simple blood test to predict those most at risk of Alzheimer’s disease and suitable for taking part in prevention trials. The Swedish part of this study was supervised by Dr Thomas Gustafsson, MD, PhD, Associate Professor at the Department of Laboratory Medicine, Karolinska Institutet. The project was funded by the Swedish Research Council, the Wallenberg Foundation, Sweden, the Medical Research Council (MRC), UK, National Institutes of Health (NIH), US, and the Innovative Medicines Initiative (IMI), a joint undertaking between the European Union and the pharmaceutical industry association EFPIA. This news article is an abbreviation of a press release from MRC.   Publication A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status Sanjana Sood, Iain J Gallagher, Katie Lunnon, Eric Rullman, Aoife Keohane, Hannah Crossland, Bethan E Phillips, Tommy Cederholm, Thomas Jensen, Luc JC van Loon, Lars Lannfelt, William E Kraus, Philip J Atherton, Robert Howard, Thomas Gustafsson, Angela Hodges and James A Timmons Genome Biology 2015, 16:185, online 7 September 2015,  doi:10.1186/s13059-015-0750-x

Surgery with mosquito mesh may reduce the suffering of millions

Mon, 07/09/2015 - 12:12
Mosquito mesh can prevent malaria, but also be used to reduce the suffering of millions of poor people in other ways. Through a collaboration of researchers at Umeå University, Karolinska Institutet and Makerere University in Uganda, it has been shown that mosquito mesh can be used safely in groin hernia surgery. The findings are being presented in a new doctoral thesis. “Mosquito mesh with the purpose of catching mosquitoes can now be used to prevent the intestines from falling through the hole in the abdominal wall”, says Jenny Löfgren, a doctoral student at the Department of Surgical and Perioperative Sciences, Umeå University, and author of the thesis. “This progress means that even the poor can benefit from the network-based surgical technique used in high-income countries.” Over 200 million people suffer from groin hernia worldwide. Without surgery, groin hernias can cause much suffering and about 40 000 people die from this condition every year. Groin hernia repair is among the most commonly performed surgical procedures on the planet. Around 20 million hernia repairs are performed every year – but over 180 million are not operated. The majority of those who do not benefit from surgery are poor and live in Low and Middle Income Countries. In Uganda, for instance, over six per cent of adult men have a groin hernia but less than one in a hundred groin hernia patients are operated per year. Instead of the expensive mesh In western countries, hernias are mostly repaired using a synthetic commercial mesh. Mesh repairs have proven unequalled compared to previous surgical methods, but the mesh costs 100 US Dollars or more. Such an expense is insurmountable to the world’s poor. According to Jenny Löfgren, this is where the mosquito mesh has its potential, as it can be used instead of the expensive mesh. Mosquito mesh is already used in groin hernia surgery in some places but the safety and effectiveness of this practice has hardly been evaluated. The current research project compared expensive commercial mesh with mosquito mesh. Almost all the 300 patients were followed for one year and there were no differences in terms of complications, hernia recurrence or patient satisfaction. “Therefore, our study provides solid evidence that the mosquito mesh can be safely used for the treatment of groin hernia”, says Jenny Löfgren. “Now, a superior surgical method can also be provided for poor patients at a fraction of the cost of the expensive mesh. These findings may benefit the many millions of groin hernia patients living in Low and Middle Income Countries.”   This doctoral thesis will be presented at Umeå university on September 17th, 2015. Supervisor has been Dr Andreas Wladis, MD, PhD, at the Department of Clinical Science and Education, Södersjukhuset at Karolinska Institutet. Learn more in a press release from Umeå University More about Karolinska Institutet's collaborations in Uganda Doctoral thesis Groin hernias and unmet need for surgery in Uganda - epidemiology, mosquito nets and cost effectiveness Jenny Löfgren, Umeå University 2015, ISBN: 978-91-7601-316-8

Pioneer and donor Endre A. Balazs has passed away

Fri, 04/09/2015 - 13:13
Professor Endre Alexander Balazs, physician, scientist, innovator and entrepreneur, died August 29 in France, aged 95. Earlier this year, professor Balazs and his wife, Dr Janet L. Denlinger, donated 4 million dollars for the establishment of a Professorship in Innovation and Entrepreneurship at Karolinska Institutet. The couple visited Karolinska Institutet in May to attend the ceremony at which the deed of gift was signed. Professor Balazs, called “Bandi”, dedicated his life to research on the structure and biological activity of the polysaccharide hyaluronan. In the 1940s, he successfully extracted the substance in large volumes from cockscombs. He was the founder of companies that contributed to the development of the therapeutic application of hyaluronan in cataract operations, which as of today have improved the eyesight of hundreds of millions of patients. Hyaluronan is also used in the treatment of osteoarthritis and facial wrinkles. The Endre A. Balazs Professorship in Innovation and Entrepreneurship made possible by the donation will contribute to the development and commercialisation of research discoveries for the benefit of society. Read more about the donation on KI News, May 13, 2015: “Karolinska Institutet creates a new professorship in innovation and entrepreneurship“

Two KI researchers receive Anders Jahre‘s Awards for Medical Research

Fri, 04/09/2015 - 11:11
Two of the four winners of Anders Jahre‘s Awards for Medical Research are researchers at Karolinska Institutet. The awards are among the largest within Nordic biomedical research. Professor Rikard Holmdahl at the Department of Medical Biochemistry and Biophysics and professor Ludvig M. Sollid at the University of Oslo share the Anders Jahre Senior Medical Prize, including a grant of NOK 1,000,000. They receive the award in recognition of their pioneering research in the field of autoimmune diseases. Professor Pernilla Lagergren at the Department of Molecular Medicine and Surgery is awarded Anders Jahre‘s Prize for Young Scientists. She is awarded the prize for her ”groundbreaking research on factors that affect survival and quality of life following cancer surgery”. The grant of NOK 400,000 is shared with dr Kaisa Haglund at the Oslo University Hospital. Anders Jahre‘s Awards for Medical Research honour excellent research in basic and clinical medicine. They are awarded annually by a committee at the University of Oslo.  

Study reveals the genetic start-up of a human embryo

Thu, 03/09/2015 - 12:12
An international team of scientists led from Sweden’s Karolinska Institutet has for the first time mapped all the genes that are activated in the first few days of a fertilised human egg. The study, which is being published in the journal Nature Communications, provides an in-depth understanding of early embryonic development in human – and scientists now hope that the results will help finding for example new therapies against infertility. At the start of an individual’s life there is a single fertilised egg cell. One day after fertilisation there are two cells, after two days four, after three days eight and so on, until there are billions of cells at birth. The order in which our genes are activated after fertilisation has remained one of the last uncharted territories of human development. There are approximately 23,000 human genes in total. In the current study, scientists found that only 32 of these genes are switched on two days after fertilization, and by day three there are 129 activated genes. Seven of the genes found and characterised had not been discovered previously. “These genes are the ‘ignition key’ that is needed to turn on human embryonic development. It is like dropping a stone into water and then watching the waves spread across the surface”, says principal investigator Juha Kere, professor at the Department of Biosciences and Nutrition at Karolinska Institutet and also affiliated to the SciLifeLab facility in Stockholm. The researchers had to develop a new way of analysing the results in order to find the new genes. Most genes code for proteins but there are a number of repeated DNA sequences that are often considered to be so-called ‘junk DNA’, but are in fact important in regulating gene expression. Treatment of infertility In the current study, the researchers show that the newly identified genes can interact with the ‘junk DNA’, and that this is essential to the start of development. “Our results provide novel insights into the regulation of early embryonic development in human. We identified novel factors that might be used in reprogramming cells into so-called pluripotent stem cells for possible treatment of a range of diseases, and potentially also in the treatment of infertility”, says Outi Hovatta, professor at Karolinska Institutet’s Department of Clinical Science, Intervention and Technology, and a senior author. The study was a collaboration between three research groups from Sweden and Switzerland that each provided a unique set of skills and expertise. The work was supported by the Karolinska Institutet Distinguished Professor Award, the Swedish Research Council, the Strategic Research Program for Diabetes funding at Karolinska Institutet, Stockholm County, the Jane & Aatos Erkko Foundation, the Instrumentarium Science Foundation, and the Åke Wiberg and Magnus Bergvall foundations. The computations were performed on resources provided by SNIC through Uppsala Multidisciplinary Center for Advanced Computational Science (UPPMAX). View out press release about this study Publication Novel PRD-like homeodomain transcription factors and retrotransposon elements in early human development Virpi Töhönen, Shintaro Katayama, Liselotte Vesterlund, Eeva-Mari Jouhilahti, Mona Sheikhi, Elo Madissoon, Giuditta Filippini-Cattaneo, Marisa Jaconi, Anna Johnsson, Thomas R. Bürglin, Sten Linnarsson, Outi Hovatta and Juha Kere Nature Communications, 3 September 2015, doi: 10.1038/NCOMMS9207

New mechanism discovered behind infant epilepsy

Thu, 03/09/2015 - 11:11
Scientists at Karolinska Institutet and Karolinska University Hospital have discovered a new explanation for severe early infant epilepsy. Mutations in the gene encoding the protein KCC2 can cause the disease, hereby confirming an earlier theory. The findings are being published in the journal Nature Communications. Through large-scale genetic analyses of a family with two affected children at SciLifeLab in Stockholm, mutations were identified in the gene encoding the transport protein KCC2. In a collaboration with scientists at the University College London, another family with children carrying mutations in the same gene was further identified. Two of the children in each family demonstrated similar symptoms that can be connected to a severe variant of infant epilepsy with MPSI (Migrating Partial Seizures of Infancy). “Epilepsy occurs in many different forms. Earlier associations with KCC2 have been observed, such as a downregulation of the protein after brain damage that increases the tendency for seizures, but firm evidence for this disease mechanism has been lacking so far”, says Anna Wedell, senior physician at Karolinska University Hospital and professor at the Department of Molecular Medicine and Surgery at Karolinska Institutet. “Through our discovery we have been able to prove that a defective function of the KCC2 protein causes epilepsy and hence that an imbalance in the brain’s chloride ion regulation system can be the reason behind the disease. The next step is to investigate to which extent this imbalance occurs in more common variants of epilepsy.” KCC2 constitutes a chloride channel specifically localized in the brain and have earlier been shown to play a major role in synaptic inhibition by maintaining a low concentration of chloride ions inside the neurons. Normally the amount of KCC2 increases shortly after birth, causing the signal substance GABA to switch from being stimulating to being inhibitory. GABA remain stimulatory “Mutations in the gene encoding KCC2 prevent this switch which makes GABA remain stimulatory, incapable of inhibiting the signals of the brain”, says Dr. Wedell. “The neurons then discharge at times, when they normally should not, giving rise to epilepsy.” By conducting detailed investigations of cells expressing both the normal and the mutated forms of KCC2, the scientists demonstrated that the identified mutations led to disrupted chloride ion regulation and that an imbalance in this system thus brings about severe infant epilepsy, a potentially treatable disease. “Clinical trials are ongoing with a drug that, if successful, will compensate for the disrupted regulation and ameliorate the disease in small children with epilepsy, says Dr. Wedell.”      First study-author of the current study is Tommy Stödberg, a senior physician at Astrid Lindgren's Childrens Hospital, Karolinska University Hospital, and doctoral student at the Department of Women's and Children's Health, Karolinska Institutet. The study was financed by the Swedish Research Council, Karolinska Institutet, Stockholm County Council, Swedish Brain Foundation, and the Knut and Alice Wallenberg Foundation. Text: Frida Wennerholm View our press release about this study More about Anna Wedell's research Publication Mutations in SLC12A5 in epilepsy of infancy with migrating focal seizures Tommy Stödberg, Amy McTague, Arnaud Ruiz, Hiromi Hirata, Juan Zhen, Philip Long, Irene Farabella, Esther Meyer, Atsuo Kawahara, Grace Vassallo, Stavros Stivaros, Magnus Bjursell, Henrik Stranneheim, Stephanie Tigerschiöld, Bengt Persson, Iftikhar Bangash, Krishna Das, Deborah Hughes, Nicole Lesko, Joakim Lundeberg, Rodney Scott, Annapurna Poduri, Ingrid Scheffer, Holly Smith, Paul Gissen, Stephanie Schorge, Maarten Reith, Maya Topf, Dimitri Kullmann, Robert Harvey, Anna Wedell, and Manju Kurian Nature Communications online 3rd August 2015, doi: 10.1038/NCOMMS9038

Miriam Elfström receives Dimitris N. Chorafas Prize

Wed, 02/09/2015 - 10:10
Miriam Elfström, previously a doctoral student at the Department of Medical Epidemiology and Biostatistics has received the Dimitris N. Chorafas Prize for 2015 for her dissertation Optimizing cervical cancer prevention through screening and HPV vaccination. In her thesis she describes, among other things, the long term efficacy of different screening strategies and the long term risks associated with HPV infection, the quality of different screening programmes and their organization, as well as the efficacy of different vaccination strategies. The aim of the research is to maximize the benefit of prevention initiatives in Sweden and Europe. As a doctoral student Miriam Elfström was the first author of an article in the British Medical Journal and co-author of an article in the Lancet. After her doctoral studies, Miriam Elfström is working as a postdoctoral researcher at the Department of Laboratory Medicine at Karolinska Institutet and process leader for cancer prevention at the Regional Cancer Centre Stockholm-Gotland region. More about her research. The Dimitris N. Chorafas Foundation was founded in  1992 and since 1996 the Foundation has a collaboration with 23 partner universities, including Karolinska Institutet. The subject area ‘medical science’ focuses on new PhD holders or doctoral students who are in the final phase of their doctoral work. The candidates should not be above 30 years of age during their public defence.

Children with ASD should receive a molecular diagnosis

Wed, 02/09/2015 - 08:08
Children with autism spectrum disorder should be given more thorough medical examinations and genetic tests that cover the entire genome as soon as possible after their clinical diagnosis. This will facilitate more exact molecular diagnoses, which can inform families about biological causes of the disorder and help the children obtain better care. This according to a paper by Swedish and Canadian researchers published in the scientific journal JAMA. Autism spectrum disorder (ASD) is an umbrella term for different types of autism of varying degrees of severity, of which all are considered neuropsychiatric functional impairments and are characterised by social communication and interaction difficulties as well as limited interests and stereotypical behaviour. It has long been known that co-morbidity with ASD is high: over 70 per cent of all children with the disorder have one or more other psychiatric or medical diagnoses. A group of Swedish and Canadian researchers now claim that children with ASD should routinely be offered early genetic analyses – chromosomal microarray and whole-exome sequencing – to make a molecular diagnosis by identifying the genetic abnormality causing the functional impairment. Abnormalities in specific genes The present study involved 258 Canadian children given ASD diagnoses between 2008 and 2013. By only examining the children medicinally or by means of a medical examination combined with a search for abnormalities in specific genes, the team was able to make a molecular diagnosis for one in twenty children. However, when they conducted broader genetic analyses, this number increased. The researchers employed two different methods, chromosomal microarray and a more recent technique called whole-exome sequencing, which can analyse the entire genome. Using these methods, the team was able to give almost 16 per cent of the children an exact molecular diagnosis. None of the children had the same genetic disorder, demonstrating the complexity and heterogeneous nature of the factors underlying ASD. “Our data suggests that children with ASD should be offered a genetic examination that covers the entire genome,” says the paper’s lead author Kristiina Tammimies, researcher at the Department of Women's and Children's Health, and affiliated to the Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND). “For families, it can be important to understand the biological reason for the disorder and get guidance of possible increased risk for same disorder in younger siblings. We also know that certain genetic anomalies behind ASD are associated with conditions like obesity or diabetes, so the more we learn the more we will be able to provide care at an individual level.” Whole-exome sequencing techniques About 20 per cent of the 258 children had more than five minor physical abnormalities, such as a single palmar crease, uncommonly low-set ears and/or congenital deformities (e.g. heart defects). In this subgroup of children, the researchers were able, using both chromosomal microarray and whole-exome sequencing techniques, to identify a molecular diagnosis in 40 per cent of the children. “If there is a need to prioritise which children should receive these two genetic diagnostic tests, it would the children with more complex clinical symptoms, by which I mean those who have these physical abnormalities or congenital defects in addition to ASD,” says Dr Tammimies. “As in this group we had the best success on making a molecular diagnosis.” The project was financed with grants from several bodies, including the Swedish Research Council, and was conducted with researchers from the Memorial University of Newfoundland and SickKids Hospital in Toronto, Canada.  View the journal's video about this study Press release from SikKids Hospital More about Karolinska Institutet's collaborations in Canada Publication Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children with Autism Spectrum Disorder Kristiina Tammimies, Christian R. Marshall, Susan Walker, Gaganjot Kaur, Bhooma Thiruvahindrapuram, Anath C. Lionel, Ryan K. C. Yuen, Mohammed Uddin, Wendy Roberts, Rosanna Weksberg, Marc Woodbury-Smith, Lonnie Zwaigenbaum, Evdokia Anagnostou, Zhuozhi Wang, John Wei, Jennifer L. Howe, Matthew J. Gazzelone, Lynette Lau, Wilson W. L. Sung, Kathy Whitten, Cathy Vardy, Victoria Crosbie, Brian Tsang, Lia D’Abate, Wai Tong, Sandra Luscombe, Tyna Doyle, Melissa T. Carter, Peter Sztarmari, Susan Stuckless, Daniele Merico, Dimitri Stavropoulos, Stephen W. Scherer and Bridget A. Fernandez JAMA, online September 1, 2015

Oliver Sacks, neurologist and honorary doctor at KI, wrote “epoch-making books”

Mon, 31/08/2015 - 16:16
Oliver Sacks is dead. The world-famous doctor was many things. He was, for example, professor of neurology at the NYU School of Medicine in New York, USA, and the best-selling author of several books, including Awakenings, which was later made into a successful film. In 2003 Oliver Sacks was made honorary doctor of medicine at Karolinska Institutet. Oliver Sacks passed away on Sunday 30 August after a long battle with cancer. He told the New York Times last February that the melanoma in his eye had metastasised and that he had only a few months left to live. By the time he was made honorary doctor of medicine at Karolinska Institutet in 2003 he had written a number of popular books on his neurology patients, his collection of essays on memory loss titled “The Man Who Mistook His Wife for a Hat” being regarded by many as a literary classic. The New York Times has called him “The Poet Laureate of Medicine”. The decision to make Oliver Sacks an honorary doctor of medicine at KI was taken in acknowledgement of the way his works aroused such widespread interest in patients with neurological disorders, such as sleeping sickness, Tourette’s syndrome, acquired colour-blindness, autism and Alzheimer’s disease. “His writings are epoch-making in that they combine immense scientific knowledge with a subjective insight into the patients’ problems,” wrote the Board of Research in 2003 in its announcement. The board also commended him for “combining his clinical skills in neurology with an astute eye and a unique talent for writing and story-telling. In this way, he combines medical science with humanist insight into his patients’ suffering.” When he came to Sweden to receive his doctor’s hat at Karolinska Institutet, he took the opportunity to follow in the footsteps of his childhood heroes, the chemists Scheele and Berzelius, and to lay a wreath at Scheele’s grave in Köping. Oliver Sacks was 82.

Visiting Professor at Karolinska Institutet cleared from suspicions of scientific misconduct

Fri, 28/08/2015 - 11:11
After a detailed and lengthy investigation, the Vice-Chancellor of Karolinska Institutet has pronounced his decision on a high-profile case of claimed scientific misconduct. Vice-Chancellor  Anders Hamsten has concluded that while on some points Visiting Professor Paolo Macchiarini did act without due care, it does not qualify as scientific misconduct. “Now that we have examined the allegations of scientific misconduct in all seven indicted articles, we have found that they contain certain flaws but nothing that can be considered scientific misconduct,” says Vice-Chancellor Anders Hamsten. The complaints against Professor Macchiarini were lodged by four physicians at Karolinska University Hospital who were themselves part of the research environment and, in some cases, co-authors of the articles that were reported for scientific misconduct. The complaints were submitted in June, August and September 2014, prompting an inquiry by Karolinska Institutet’s Vice-Chancellor in accordance with the provisions of the Higher Education Ordinance and the university’s own rules for dealing with cases of alleged scientific misconduct. Concerns were raised The first paper describes the manufacture of a synthetic oesophageal prosthesis and its functionality on transplantation into a rat. The concerns raised by the complainants include the conclusions of the functionality of this prosthesis and the interpretation of CT scans.  The six other papers describe transplantations of a synthetic tracheal prosthesis in humans, namely three patients with tracheal diseases who were beyond the help of conventional surgery and who were given synthetic trachea coated with their own bone-marrow derived stem cells at Karolinska University Hospital. Here, the complainants pointed out that the results concerning the patients’ clinical progress as expressed in the papers did not match the patients’ medical records as kept at Karolinska University Hospital, and that there was no evidence that a synthetic tracheal transplant can develop into a functional airway. They also questioned the claim that the first patient had suffered a relapse of his tracheal cancer and that surgery was therefore necessary. A statement of opinion was requested As part of the inquiry, a statement of opinion was requested from Professor emeritus Bengt Gerdin, who, on examining the documents and information included in the complaint, Professor Macchiarini’s initial response and the medical records from Karolinska University Hospital, submitted his conclusion in mid-May that the accused was indeed guilty of scientific misconduct. Following the detailed report submitted by Professor Gerdin, Professor Macchiarini and his co-authors submitted over 1,000 pages of comments and documents, including medical records from the first patient’s doctors in Iceland, showing that on the crucial points, the description of his condition given in the articles is correct. “Bengt Gerdin’s examination was extremely valuable for the inquiry, but the documents to which he had access lacked significant data on the pre- and postoperative status of two of the patients,” says Professor Hamsten. “The comments sent in by Professor Macchiarini and his co-authors have had a significant influence on how the case has been assessed. Now that we have all the relevant material on hand, we have a much clearer picture of what happened.” In their complaint, the four physicians also criticised Professor Macchiarini for not having obtained a permit from the regional Ethical Review Board and the Swedish Medical Products Agency before the operation. However, Karolinska Institutet did not examine this issue in its inquiry since the Swedish Research Council’s definition of scientific misconduct does not cover breaches of the Ethical Review Act and the Medicinal Products Act. At the same time, Karolinska Institutet concluded that a decision to perform the three operations was taken by the hospital. “Karolinska University Hospital made the decision to operate following a transparent process and in what it saw as the absence of alternative therapeutic solutions,” says Professor Hamsten. “These decisions did not address research aspects.” Interaction between hospital and university needs improvements The inquiry shows that the interaction between Karolinska Institutet and Karolinska University Hospital has not functioned satisfactorily, and the Vice-Chancellor’s decision promises improvements to procedures, regulations and support structures for clinical trials and clinical therapy research. The line between clinical application and research when it comes to experimental therapy will need to be better defined, and clearer guidelines for academic research and academic healthcare will be drafted. Professor Macchiarini has also been instructed to submit errata to the journals that published some of the scientific papers to clarify and rectify the failings that the inquiry has brought to light. “Some aspects of Paolo Macchiarini’s research do not meet our high quality standards,” says Professor Hamsten. “We will now be remedying the deficiencies our inquiry uncovered with him, the heads of his department and representatives from Karolinska University Hospital.”  

Reproducibility of research in psychology investigated

Fri, 28/08/2015 - 09:09
An international study presented in Science Magazine questions the reproducibility of much of the published findings in psychology journals. Researchers tried to replicate 100 studies from three prominent journals, and found that regardless of the analytic method or criteria used fewer than half of their replications produced the same findings as the original study. “A failure to reproduce does not necessarily mean that the original report was incorrect, but this shows the challenges of reproducing research findings”, says study co-author Gustav Nilsonne, MD, PhD, affiliated to the Stress Research Institute at Stockholm University, and to Karolinska Institutet. “Scientific evidence should not depend on trusting the person that made the discovery, rather on credibility accumulating through independent replication and the elaboration of ideas and evidence.” The so-called Reproducibility Project: Psychology was launched in 2011, and has since resulted in similar efforts within other research areas. The current study is the largest systematic investigation of reproducibility ever made in any research field. The team behind it consists of 270 researchers from all over the world, who have contributed through crowdsourcing, which is unique in itself. “In the present academic culture, scientists’ main incentive is to publish as many scientific papers in high impact journals as possible”, says Gustav Nilsonne. "Research presenting new and surprising findings is more likely to be published, even at the cost of reproducibility of the findings. However, what is good for science and what is good for scientists, is not always the same thing, and vice versa. Therefore, we need more transparency and openness about methods and research data, so that independent review and replication is possible.” Press release from the Center for Open Science Editorial comment about the findings News article in The Atlantic Publication Estimating the reproducibility of psychological science – Open Science Collaboration  Science 28 August 2015: Vol. 349 no. 6251, DOI: 10.1126/science.aac4716

Circadian genes go to sleep every day at the periphery of the nucleus

Fri, 28/08/2015 - 08:08
Mobility between different physical environments in the cell nucleus regulates the daily oscillations in the activity of genes that are controlled by the internal biological clock, according to a study that is published in the journal Molecular Cell. Eventually, these findings may lead to novel therapeutic strategies for the treatment of diseases linked with disrupted circadian rhythm. So called clock-controlled – or circadian – genes are part of the internal biological clock, allowing humans and other light-sensitive organisms to adjust their daily activity to the cycle of daylight and darkness. In the current study, investigators at Karolinska Institutet found that daily changes in the spatial localisation of clock-controlled genes in the cell nucleus regulates fluctuations in their activity with a 24-hour period length. “We have uncovered a novel principle of circadian transcriptional regulation that involves a so-far unexpected dynamics in the sub-nuclear positioning of circadian genes”, says principal investigator Anita Göndör at the Department of Microbiology, Tumor and Cell Biology at Karolinska Institutet. Follows a pattern The genetic material is packaged in a structure called chromatin in the cell nucleus. It has been established that the 3-dimensional distribution of chromatin in the nucleus follows a pattern. Open chromatin containing active genes tends to occupy the central parts, whereas chromatin containing genes that are not active tends to localise to the peripheral parts of the nucleus – an environment rich in factors that promote gene silencing. Researchers investigated physical meetings between regions that are located far apart from each other on the linear chromatin fibre or reside on different chromosomes. By studying such encounters in the 3-dimensional space of the nucleus, they discovered a network of contacts between clock-controlled genes and domains of gene-poor, repressed chromatin in the periphery of the nucleus. They identified two proteins that bring the genes to bed and help them go to sleep at the periphery of the cell nucleus every day: poly(ADP-ribose) polymerase 1 (PARP1), a well-known regulator of DNA repair and gene expression, and the transcription factor CTCF. The researchers thus found that PARP1 and CTCF promote the diurnal recruitment of circadian genes to the nuclear periphery to attenuate their expression. They were then released from the periphery in a silent, ‘sleeping’ state to start a new cycle. Multifactorial diseases The internal biological clock regulates, among other things, body temperature, metabolism and the levels of several hormones. Disruption of circadian rhythm has been linked to predisposition to multifactorial diseases, such as diabetes mellitus, metabolic syndrome, psychiatric disorders and cancer. The new knowledge may lead up to new strategies for treatment of diseases that are affected by deregulated circadian rhythm. The research was supported by the Swedish Research Council, the Swedish Pediatric Cancer Foundation, the Swedish Cancer Foundation, the Lundberg Foundation, Karolinska Institutet, and the KA Wallenberg Foundation. Researchers from SciLifeLab, and University of Pécs in Hungary also contributed to the current study. View our press release about this study More about Anita Göndör´s research group Publication PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin  at the Lamina Promote Oscillating Transcription Honglei Zhao, Emmanouil G. Sifakis, Noriyuki Sumida, Lluís Millán-Ariño, Barbara A. Scholz, J. Peter Svensson, Xingqi Chen, Anna L. Ronnegren, Carolina Diettrich Mallet de Lima, Farzaneh Shahin Varnoosfaderani, Chengxi Shi, Olga Loseva, Samer Yammine, Maria Israelsson, Li-Sophie Rathje, Balázs Németi, Erik Fredlund, Thomas Helleday, Márta P. Imreh, and Anita Göndör Molecular Cell, publishing in the 17 September, 2015 paper issue, online 27 August 2015