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An international team of scientists, led from Karolinska Institutet, has investigated the neural basis of racial biases. The results, published in the scientific journal NeuroImage, show that after an aversive experience, differences in brain activity are seen, depending on whether the experience is associated with a member of the person’s own ethnic group or another. People are good at putting people and items into categories. From an evolutionary perspective, it has always been advantageous to be able to quickly determine if something is a danger or an asset. This can however be a problem today since it can lead to unfounded biases. Psychologists use the terms ingroup and outgroup to differentiate between the group you belong to versus all other groups. Scientists have previously shown that we acquire and express fear differently based on the racial identity of a person we learn something about. However, the brain mechanism of these biases has not been studied previously. “Based on what we already know about fear learning, we expected differential brain responses to racial ingroups and outgroups” says Tanaz Molapour, doctoral student at the Department of Clinical Neuroscience, and lead author of the study. “As expected, our results show that there are differences in brain activity after aversive experiences, depending on whether the experience was associated with the ingroup or outgroup.” In the study, 20 white participants were presented with images of two black and two white faces each. One face of each racial group was paired with a mildly unpleasant electrical stimulation, representing an aversive experience. Next, participants watched all the faces again without any shocks being administered, so that the participants learned that the faces were safe. Two days later, the participants took part in a social interactive ball-tossing task, with images of faces of new black and white individuals. Learning responses were measured through physiological arousal, brain responses and behaviour. The researchers found two brain areas in particular, the amygdala and the anterior insula, that played key roles in differentiating between ingroup and outgroup faces. The results show that some of the participants had exaggerated memories of aversive experiences associated with outgroup faces. The brain responses predicted later expressions of discriminatory behaviour towards new outgroup members. According to Associate Professor Andreas Olsson, the principle investigator behind the study, these findings may help us to better understand the brain mechanisms by which small biases based on an aversive experience with a member of another social or ethnic group may turn into a xenophobic response. This study was funded by the Swedish Research Council and the European Research Council. Publication  Neural correlates of biased social fear learning and interaction in an intergroup context Tanaz Molapour, Armita Golkar, Carlos David Navarrete, Jan Haaker, Andreas Olsson NeuroImage, online 10 July 2015  

Team-based learning (TBL) is a teaching method based on active learning and group work. The primary tool is discussion, which prepares the students for solving problems in their future careers. Teachers Eva Hagel and Mesfin Tessma developed an interest in TBL when they went to extend the course in medical statistics for doctoral students. They wanted to take in more students without compromising on quality. “We’d started to look for alternative teaching methods when it struck me that could shift the focus from passive lecture-based models to more active problem solving,” says Eva Hagel. “The main thing we want the students to get out of this is the ability to solve problems, not to listen to lecturers.” The method was introduced into the Centre for Learning and Knowledge at KI, where the course is held, in the autumn of 2014. On a TBL course, students work in teams of five or six, and the classes are based on problem-assignments that the students prepare at home and then discuss with the aim of reasoning their way to a solution. The group dynamic is quite an important aspect of TBL. The members of a group represent different qualities and backgrounds, and this, hopefully, stimulates cooperation and discussion. The teachers are visible in the classroom but are really meant to let the groups arrive at the answers unaided. “It’s been a challenge for us teachers, since we’re more used to guiding the conversation, asking the questions and often answering them too,” says Ms Hagel. “Now when  get asked something by a group, I try to throw it over to the next group and then we try to reach some kind of consensus together where everyone feels that they’ve been involved in the discussion and produced an answer.” “Many students seem to be more motivated by this active teaching,” says course coordinator Mesfin Tessma. “They get immediate feedback which is very confidence-boosting – and educational. TBL is meant to be fun, and we constantly get something back from the students, which makes us feel energised and motivated too.” I can always get support from the group if there’s something I don’t quite get In the Strix room on the Solna campus, the students sit deep in discussion. They are on the foundation course in medical statistics for doctoral students that is being held along the lines of the team-based learning concept. The course is the first at KI held exclusively as TBL. Similar methods are used at other Swedish universities, but for the students on this course it is a totally new experience. “In Spain, we don’t have TBL as far as I’m aware, but I definitely think that this kind of teaching has its advantages,” says one of the exchange students Sandra Petrus-Reurer. “After all, it’s a very intensive method.” “This is my first TBL course, but I’ve done problem-based learning (PBL) before, which is like TBL,” says David Forsberg, another student on the course. Much thought has clearly gone into how the groups have been divided up, as there is a mix of age, origin and background. Everyone agrees that it is important to have a good group in which everyone is on the same level and no one has to be the one with all the answers or, indeed, all the questions. “We’ve got a group that’s really equal and that often tackles the problem in the same way, and I can always get support from the group if there’s something I don’t quite get,” says Angelina Schwarz, exchange student from Germany. The medical statistics course is only two weeks long and is very intensive. Opinions differ, however, as to whether doctoral students would choose TBL for their other courses. “I prefer to study alone, because I can go at my own pace and don’t have to bother about anyone else, and no one else has to bother about me,” says Angelina Schwarz. “I like the set-up and would definitely choose TBL or PBL over regular teaching,” says David Forsberg. However, everyone agrees that TBL doesn’t suit every aspect of their education. Sandra Petrus-Reurer says that it also depends on how much time you have. “If you go to all the lectures maybe the only time you put into the course is lecture time,” she says. “When you’re studying on a TBL course, quite a lot of your spare time goes into studying, time that you might want to spend doing something else.” Text: Frida Wennerholm Photo: Gunnar Ask    

They created headlines last February when their art collection fetched 130 million kronor. Now KI alumni Gunnar Höglund and Anna-Stina Malmborg explain why they are donating some of the money to their KI foundation, and why it’s so important to research into educational methods. Moderna Museet and Karolinska Institutet are to receive a generous donation from the couple after their valuable collection went under the hammer at Sotheby’s in London. For KI’s part, the recipient is the increasingly capital-strong Gunnar Höglund and Anna‑Stina Malmborg foundation, which funds the Karolinska Institutet prize for medical education research. “We’re doing it because we believe that education’s important,” says Dr Höglund. “Our intention is to direct attention onto research in this field.” Art has always been a big interest of theirs, and they have been building their collection since the 1960s. But now that they have served their purpose, the couple want to use the money for something else. That their KI foundation has received an injection of 12 million kronor guarantees that it will continue to be able to award a prize that is large enough to attract international attention. The prize of almost 50,000 euro – almost half a million kronor – goes to researchers who conduct high-quality research in the field of medical education. “Education is fundamental when it comes to everything from basic subject knowledge to skills and attitudes, including how to interact with patients,” says Dr Höglund. “It shapes us – and is researchable too.” Since training to be doctors at Karolinska Institutet, the couple can see that pedagogical development has made great strides forwards. Drs Malmborg and Höglund was part of the ’68-wave, when academics threw all education into dispute, not least students of education such as them. For their entire professional lives, they taught in their respective fields. Anna-Stina worked as a teacher and researcher in bacteriology, and Gunnar worked as a senior lecturer in physiology; he later became a professor at the National Institute for Working Life while variously engaged in pedagogical development at KI. “Education is one of the primary missions of the university, but is often somewhat neglected; research is a bit sexier,” says Dr Höglund. One possible explanation for this is that the people who are made professors are highly qualified in their field of research – but not necessarily in teaching. The fact that research generates new knowledge while education recycles existing knowledge maybe cannot be ignored either, they reason. Moreover, patients and administration must often come first. “We use very few resources to develop education. There is no other area within medicine that is not evidence based.” And this is where the foundation’s prize comes in. It was established in 2001 to reward research that has the potential to deliver long-lasting improvements to the education and training of all healthcare professionals. Seven researchers have won the prize to date for their work on medical education. Ultimately, it’s a matter of producing more skilled practitioners and improving the care they provide. “Not much financial support goes into this, which is why we want to do this,” says Dr Höglund. Text: Madeleine Svärd Huss Photo: Gustav Mårtensson Read more: Karolinska Institutet Prize for Research in Medical Education

Hereditary angioedema type III is a rare, hereditary, and serious disorder, characterised by painful swellings in the skin and other organs. An international team of scientists have published a study in The Journal of Clinical Investigation, where they show that the disease is caused by a defective blood protein, the so-called coagulation factor XII. The results from this study may contribute to future treatment strategies for patients with the disease. Oedema, or tissues becoming swollen due to fluid retention, is a common symptom in a number of pathologies such as allergies or kidney and heart diseases. The swelling is caused by blood vessels leaking fluid into the surrounding tissue. In hereditary angioedema (HAE), the leakage, and hence the swelling, is primarily caused by the hormone bradykinin. HAE is a serious disease with painful episodes of swelling typically involving the skin and gastrointestinal tract. The attacks can be life-threatening since the airways may become obstructed due to the swelling. The most common variants of the disease are called HAE type I and II, and the cause of these are well known. “HAE type III was discovered just recently. If we want to treat the disease, we must first understand the underlying mechanism”, says Dr Jenny Björkqvist at the Department of Molecular Medicine and Surgery, Karolinska Institutet, one of the researchers behind the study. The researchers already knew that patients with HAE type III have a mutation in the blood protein factor XII – but they didn't know why this would cause swellings. In the current study, the researchers discovered that a single sugar was missing in the mutated factor XII in HAE type III patients. The mutated factor XII was found to be overactive. This caused an excess of bradykinin production, resulting in vessel leakage and swelling. There are natural inhibitors in blood that normally prevent factor XII from becoming activated. These inhibitors can also bind to and inhibit the mutated factor XII, but this is not enough to completely stop the overactivation. “We realised that we had to find substances that could block factor XII more effectively. We have previously made an antibody that can inhibit factor XII, and shown that this antibody blocks factor XII driven blood clot formation. In the current study, we demonstrate that the same agent prevents oedema in mice”, says Dr Thomas Renné at the Department of Molecular Medicine and Surgery, Karolinska Institutet, principal investigator of the study. The researchers hope that the study results can be used to establish the first treatment for patients with HAE type III – with the potential for use in a broad array of other types of swelling diseases. Participating in the study were researchers from Karolinska Institutet, Karolinska University Hospital, University Medical Center Hamburg-Eppendorf, University Medical Center Utrecht, Leibniz-Institut für Analytische Wissenschaften, Heidelberg University, University of Bonn, Univerisity Joseph Fourier, CSL Limited and CSL Behring. The research was financed with grants from the Netherlands Organization for Scientific Research (NWO), Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen, Bundesministerium für Bildung und Forschung, the Swedish Heart-Lung Foundation, Stockholm County Council, the Swedish Research Council, the German Research Society and the European Research Council. View our press release Publication  Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III  Jenny Björkqvist, Steven de Maat, Urs Lewandrowski, Antonio Di Gennaro, Chris Oschatz, Kai Schönig, Markus M. Nöthen, Christian Drouet, Hal Braley, Marc W. Nolte, Albert Sickmann, Con Panousis, Coen Maas and Thomas Renné. Journal of Clinical Investigation, online 20 July 2015, doi: 10.1172/JCI77139.

Bone marrow contains stem cells that normally give rise to new red and white blood cells. A team of researchers from Sweden and France has now shown that bone marrow cells can also form fat. The results are published in the scientific journal Cell Metabolism. While all red and white blood cells derive from stem cells in the bone marrow, the scientific community has been divided over whether bone marrow cells are also able to produce other cell types. In the present study, the researches wanted to ascertain whether cells from the bone marrow could develop into fat cells; the problem is, however, that no experimental method is available for determining the origins of these cells in humans. Using the fact that it is possible to differentiate between grafted and native cells, the researchers conducted their study on 65 adult patients of Karolinska University Hospital who had had transplants up to 31 years ago. “This is an unprecedented follow-up period and one that can therefore give us a great deal more information than the relatively short studies previously done on mice,” says Mikael Rydén, researcher at the Karolinska Institutet’s Department of Medicine in Huddinge. The results of the study, which have just been published in the journal Cell Metabolism, show that during a lifetime some 10 per cent of the graft recipients’ subcutaneous fat consisted of donor-derived cells. And while this was independent of sex and age, the patients’ BMI was an important factor in that overweight patients had up to 2.5 times more bone-marrow-derived fat cells than slim patients. According to the researchers, the results suggest that it is possible for bone marrow cells to develop into different cell types and that certain characteristics of the recipient, such as obesity, can influence this process. “The next step for us is to find out exactly which bone marrow stem cells can become fat cells,” says Professor Rydén. “These studies were done on people who had received a bone marrow transplant to treat leukaemia, and it remains to be seen if the results also apply to people who haven’t had a transplant. If they do, it could lead to new therapies for patients with metabolic diseases, in which adipose cells play a key part.” The study was financed by the Swedish Diabetes Association, the Swedish Cancer Fund, the Swedish Research Council, the Novo Nordisk Foundation, EFSD Lilly European Diabetes Research Programme, CIMED, the European Research Council and the Karolinska Institutet Strategic Research Programme in Diabetes. View our press release Publication: ‘Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis’, Mikael Rydén, Mehmet Uzunel, Joanna L. Hård, Erik Borgström, Jeff E. Mold, Erik Arner, Niklas Mejhert, Daniel P. Andersson, Yvonne Widlund, Moustapha Hassan, Christina V. Jones, Kirsty L. Spalding, Britt-Marie Svahn, Afshin Ahmadian, Jonas Frisén, Samuel Bernard, Jonas Mattsson, Peter Arner, Cell Metabolism, online 16 July 2015. 

Most wounds clear up by themselves, but some fail to heal and become chronic. An international team of researchers led from Karolinska Institutet, now unveil the important role of so-called microRNAs in regulating skin wound healing, pointing to new therapeutic possibilities for the treatment of hard-to-heal wounds. Chronic wounds affect 0.2-1% of the population in developed countries and represent an increasing health problem and an economic burden to society. Current treatments focus on optimising controllable factors such as clearing infections. There is a major medical need for treatments that have a direct impact on the wound healing process, and this is why the researchers set out to find therapeutic targets for chronic skin wounds. Wound healing is a complex process that can be divided into several phases – two of these are the inflammatory and the proliferative phase. During the inflammatory phase, damaged and dead cells, bacteria, and debris are cleared out by immune cells. Next is the proliferative phase, where skin cells multiply and there is growth of new tissue. The transition between these two phases is a critical regulatory point that can determine the outcome of the healing process. Hence, the researchers decided to look for factors that mediate this transition. MicroRNAs, or miRNAs, are short pieces of genetic code that, instead of coding for proteins, regulate the expression of genes. Since the discovery of miRNAs in 1993, many studies have shown that miRNAs are involved in a range of diseases. “There is very little known about the expression and function of miRNAs in human skin wounds, but we have previously shown that miRNAs play important roles in the regulation of the cells in the outermost layer of the skin, also called keratinocytes”, says Dr Ning Xu Landén, principal investigator at the Department of Medicine, Solna, Karolinska Institutet. The edge of wounds In a new study, published in the Journal of Clinical Investigation, the researchers collected skin biopsies from the edge of wounds, and looked for changes in miRNA expression during the healing process. They found one miRNA of particular interest, miR-132. Its expression increased during the inflammatory phase and then peaked again in the proliferative phase – just what the researchers were looking for. They found that in the inflammatory phase, miR-132 caused less immune cells to move to the wound, whereas a lack of miR-132 meant more immune cells and hence increased inflammation. During the proliferative phase, miR-132 promoted keratinocyte growth, while a lack of miR-132 decreased cell growth and wounds took longer to heal.  “Our results show that miR-132 is important during the transition from the inflammatory to the proliferative phase and therefore acts as a critical regulator of skin wound healing”, says Dr Xu Landén. “Due to its pro-healing capacity, miR-132 may be an attractive therapeutic target for chronic skin wounds. Our goal is to develop a microRNA-based treatment to promote healing.” First study-author is Dongqing Li, a postdoc at the Department of Medicine, Solna. Except researchers from Karolinska Institutet, researchers from Karolinska University Hospital, and Center for Molecular Medicine in Sweden, The Second Affiliated Hospital of Dalian Medical University, China, and Max Planck Institute for Biophysical Chemistry,Germany, contributed to the study. The research was funded by the Swedish Research Council, LA ROCHE-POSAY Foundation, Hedlunds Foundation, Welander and Finsens Foundation, the Von Kantzow Foundation, the Strategic Research Programme in Diabetes and Karolinska Institutet. View our press release about this study Publication MicroRNA-132 enhances transition from inflammation to proliferation during wound healing Healing Dongqing Li, Aoxue Wang, Xi Liu, Florian Meisgen, Jacob Grünler, Ileana R. Botusan, Sampath Narayanan, Erdem Erikci, Xi Li, Lennart Blomqvist, Lei Du, Andor Pivarcsi, Enikö Sonkoly, Kamal Chowdhury, Sergiu-Bogdan Catrina, Mona Ståhle, Ning Xu Landén J Clin Invest, online first 29 June 2015, doi:10.1172/JCI79052

24 June was the deadline for comments on Professor Emeritus Bengt Gerdins report on suspected scientific misconduct. Karolinska Institutet has received 31 replies from the co-authors of the criticized articles. All together the recently submitted material consists of circa 1.000 pages. The final process leading to a decision of the case has now begun, in which  the comments from the co-authors will be taken into consideration. Because of the vast amount of material it is today not possible to set a date for when Karolinska Institutet's decision will be made. Previous articles on the case from the KI intranet Comments on the Research Council’s decision to freeze grant payments to fraud suspect

The SciLifeLab laboratories on the Solna campus stand adjacent to the offices, and only a few paces separate Anita Aperia’s group’s white lab coats from their desks. Pernilla Lagergren and her group, on the other hand, do all their research on computers and so have no laboratory to go to. Superficially there are many differences between the two professors, but dig a little deeper and you find that their attitudes towards their professional roles are in many respects similar. Anita Aperia has been a professor for 35 years. Pernilla Lagergren took up her post only 3.5 years ago. As professors their job is to pursue research and have overall responsibility for the higher education in which they are engaged. They also appear as experts in a variety of contexts, take part in undergraduate education and sit on committees and boards. On top of all this, they have to lead their research groups and secure funding. “During the active part of my career, I sometimes felt split,” says Professor Aperia. “Now I can devote more of my time to research and supervision, but the split that can appear is dangerous.” “You have to choose and think before you say yes to everything,” says Professor Lagergren. “When you have other duties to perform, it’s your research that has to make way.” Because it was mainly their genuine interest in research that led them to where they are now, as well as the possibility of doing their own research to answer relevant questions and improve things for patients. The title of professor as such has not mattered to them. “When I started to research I had no career plan,” says Prof. Lagergren. “I was propelled into a research career by my passion for making life easier for the patients I care about. It’s the battery powering my research. You need the drive and curiosity.” They agree that patience is an indispensible quality for a professor. Setbacks are common and it is important not to lose heart when things fail to pan out as you had hoped. It is also a challenge, they say, to keep up internationally leading research and, above all, to cope with financial uncertainty. “It’s hard work sustaining a research group,” says Prof. Lagergren. “The grants are often for a couple of years and I have to apply for everything available. It’d be nice to have a certain basic security, maybe a package of resources for those employed as professors.” Prof. Aperia, who has been a researcher for her whole professional life, can compare her role now with what it was before. One difference is that there were fewer professors back in her early years. “The interesting thing is that there was more exchange going on between the faculties,” she says. “The best people in a particular field applied for advertised posts, and I think the mobility and competition was healthy.” Prof. Aperia is currently a full-time senior professor and works with a junior professor, so when she eventually retires from research, the project can continue without her. She sees it as an advantage that those who can attract grants for their research are treated as research leaders even after having reached the formal retirement age. “It’s a creative profession and it’s hard to quit. It’s like being an author or an artist. You don’t have to quit simply because you’ve reached a certain age, but you have to show that you’re doing something useful.”   Name: Anita Aperia. Title: Senior professor at the Department of Women’s and Children’s Health, KI. Time as professor: 35 years. Researches into: How to explain the energy efficiency of the body and its individual cells, with a focus on the salt pump (Na,K-ATPas), the body’s most energy-demanding protein. Name: Pernilla Lagergren. Title: Professor at the Department of Molecular Medicine and Surgery (MMK). Time as professor: 3.5 years Researches into: How recovery after oesophageal cancer surgery can be improved, based on information supplied by the patients.  Text: Karin Söderlund Leifler Photo: Gustav Mårtensson  

Colleagues from around the world came to celebrate the 90th birthdays of cancer researchers Georg and Eva Klein at a symposium that featured lectures by the world’s leading cancer researchers and opened with a special birthday concert. Eva and Georg Klein have been awarded countless prizes and awards over the years for their discoveries in the field of cancer. Although they both turn 90 this year, they are still active tumour biologists at Karolinska Institutet’s Department of Microbiology, Tumour and Cell Biology (MCT). A symposium, arranged by their students and staff, was held on 17-18 June on “The Future of Tumour Biology” at the Nobel Forum, Karolinska Institutet. The programme was kept secret from the couple up to the last minute.   “It was a delightful surprise and such a wonderful programme,” said Georg Klein during the first coffee break of the day. “Everyone is here with new discoveries. It’s so very interesting.”   The symposium was open to an exclusive collection of invited scientists but was streamed live over the internet – with the exception of the lecture by Nobel Laureate Harald zur Hausen as it contained unpublished results.   KI’s vice-chancellor, Professor Anders Hamsten, was noticeably moved when he opened the symposium by thanking the couple for what they have done for KI and for generations of researchers.   “We are here to celebrate science and to pay homage to two fantastic researchers and role models who, together, have made exceptional contributions to Karolinska Institutet and to tumour biology,” he said in his welcoming address.   Professor Hamsten described Georg and Eva Klein as two of KI’s most important researchers of all time. They were pioneers in immunotherapy, which ranks today as one of the most promising breakthroughs for the future of cancer therapy. The speakers at the symposium were the cream of modern cancer research. Apart from scientific lectures, there was also time for personal reflections on the couple’s long career. A closing address was given by Hans Wigzell, professor emeritus of immunology, and one of many to have earned their PhD under the Kleins’ supervision. He gave a vivid description of the Department of Tumour Biology that was originally set up by the couple, and that went on to become a world-leading hub of tumour biology in the 1960s and 70s, attracting scientists from all corners of the world. It also boasted a climate of trust, even for a 19-year old Hans Wigzell, who was taken on as an assistant after only his first year of medical studies.   “It’s Eva’s and George’s incredible ability to teach and inspire, not their scientific results, that is their greatest contribution to the world,” he said. “And for that we thank you, Eva, and we thank you, Georg. Text: Jenny Ryltenius Foto: Gunnar Ask  Videos from the lectures at the symposium will be available soon. Read more about Georg and Eva Klein.

Nobel laureate Shinya Yamanaka visits the Karolinska Institute and gives a lecture at a research seminar on regenerative medicine and stem cell research, which takes place June 22 at the Nobel Forum. Shinya Yamanaka at the Center for iPS Cell Research and Application (CiRA), Kyoto University, was awarded the 2012 Nobel Prize in Physiology or Medicine for his discovery that mature, specialised cells can be reprogrammed into immature stem cells, which in turn can develop into any type of cell. At the seminar, Shinya Yamanaka will talk about such induced pluripotent stem cells in the past, present and future. Stem cell research and regenerative medicine are two areas of research that have developed rapidly in recent years and bring high hopes that progress will result in new possibilities to treat a broad range of diseases.

    Scientists at Karolinska Institutet have managed to build a fully functional neuron by using organic bioelectronics. This artificial neuron contain no ‘living’ parts, but is capable of mimicking the function of a human nerve cell and communicate in the same way as our own neurons do. Neurons are isolated from each other and communicate with the help of chemical signals, commonly called neurotransmitters or signal substances. Inside a neuron, these chemical signals are converted to an electrical action potential, which travels along the axon of  the neuron until it reaches the end. Here at the synapse, the electrical signal is converted to the release of chemical signals, which via diffusion can relay the signal to the next nerve cell. To date, the primary technique for neuronal stimulation in human cells is based on electrical stimulation. However, scientists at the Swedish Medical Nanoscience Centre (SMNC) at Karolinska Institutet's Department of Neuroscience in collaboration with collegues at Linköping University, have now created an organic bioelectronic device that is capable of receiving chemical signals, which it can then relay to human cells. “Our artificial neuron is made of conductive polymers and it functions like a human neuron”, says lead investigator Agneta Richter-Dahlfors, professor of cellular microbiology. “The sensing component of the artificial neuron senses a change in chemical signals in one dish, and translates this into an electrical signal. This electrical signal is next translated into the release of the neurotransmitter acetylcholine in a second dish, whose effect on living human cells can be monitored.“Agneta Richter Dahlfors Neurologial disorders  The research team hope that their innovation, presented in the journal Biosensors & Bioelectronics,  will improve treatments for neurologial disorders which currently rely on traditional electrical stimulation. The new technique makes it possible to stimulate neurons based on specific chemical signals received from different parts of the body. In the future, this may help physicians to bypass damaged nerve cells and restore neural function. “Next, we would like to miniaturize this device to enable implantation into the human body”, says Agneta Richer-Dahlfors. “We foresee that in the future, by adding the concept of wireless communication, the biosensor could be placed in one part of the body, and trigger release of neurotransmitters at distant locations. Using such auto-regulated sensing and delivery, or possibly a remote control, new and exciting opportunities for future research and treatment of neurological disorders can be envisaged.” This study was made possible by funding from Carl Bennet AB, VINNOVA, Karolinska Institutet, the Swedish Research Council, Swedish Brain Power, Knut and Alice Wallenberg Foundation, the Royal Swedish Academy of Sciences, and Önnesjö Foundation. View our press release about this research Publication An organic electronic biomimetic neuron enables auto-regulated neuromodulation Daniel T. Simon, Karin C. Larsson, David Nilsson, Gustav Burström, Dagmar Galter, Magnus Berggren, Agneta Richter-Dahlfors Biosensors & Bioelectronics, first online 22 April 2015, Volume 71, 15 September 2015, Pages 359–364

The Swedish Research Council issued a press release this morning announcing a freeze on grant payouts to ACTREM (the Centre for Regenerative Medicine) at Karolinska Institutet. Karolinska Institutet now has three weeks to formulate an official response to this decision. The ongoing investigation into suspected scientific misconduct at Karolinska Institutet has not yet reached a conclusion. The Higher Education Ordinance charges the vice-chancellor of Karolinska Institutet with investigating such matters, and the current case is to be decided on the basis of complaints levelled against a visiting professor at KI, the expert statement of opinion submitted by the external investigator Bengt Gerdin and the comments expected from the visiting professor and the other authors of the relevant scientific papers. The deadline for these comments is 24 June. The date of Karolinska Institutet’s decision on the matter will therefore depend on the volume of material submitted and the information they contain. The Karolinska Institutet management has no further comment on the Swedish Research Council’s announcement at this juncture. The Swedish Research Council press release (in Swedish) Previous articles on the case from the KI intranet

According to an English saying, it takes a whole village to raise a child. A new study from Karolinska Institutet has shown how important the support from grandparents could be. According to the study, which is being published in Pediatric Obesity, emotional support from grandparents has a protective effect against child obesity, even with the presence of other risk factors. Previous studies have shown that the parents' socioeconomic status affects the risk of children developing obesity. But the effect of other family-related aspects on this risk has not been investigated to the same extent. Researchers from Karolinska Institutet and researchers in social anthropology at Oxford University have jointly investigated the importance of grandparental support in this context. The study included 39 preschool-aged children from Stockholm County who had received treatment for obesity. Both the mother and father of the children answered detailed questionnaires in which socio-economic status was measured by education and income levels, work and domestic situation and by how much money they had left at the end of the month. After this, they answered questions about the kinds of support – and how much – they received from their own parents, i.e. the children's grandparents. The questions aimed to establish the extent to which grandparents contributed daily support, e.g. help with washing and cleaning, financial support and emotional support, which could create a sense of being seen and understood. Received emotional support It transpired that when the parents received emotional support from their own parents, it had a protective effect against obesity in their children. Parental income is in itself linked to the BMI, Body Mass Index, in children. But the children of parents with a low income and a low level of emotional support had a higher degree of obesity than children whose parents had a low income but a high level of emotional support. “Our study shows that emotional support from grandparents may have a preventive effect against child obesity, which is a serious disease. These findings could, for instance, be incorporated into the planning of public health programmes that are aimed at reducing obesity in children. Greater social support for families with small children could help alleviate stress in parents, who will thereby be in a better position to make better food choices,” says Paulina Nowicka, Associate Professor at the Department of Clinical Science, Intervention and Technology at Karolinska Institutet. The study in question is funded by Karolinska Institutet, the Vinnmer Marie Curie International Qualification and the Princess Lovisa Foundation for Child Health Care. Publication Low grandparental social support combined with low parental socioeconomic status is closely associated with obesity in preschool-aged children: A pilot study Louise Lindberg, Anna Ek, Jonna Nyman, Claude Marcus, Stanley Ulijaszek, Paulina Nowicka Pediatric Obesity, article first published online 19 June 2015, doi: 10.1111/ijpo.12049

A new study led from Sweden’s Karolinska Institutet links male infertility to autoimmune prostatic inflammation. The findings are published in the journal Science Translational Medicine.   Involuntary childlessness is common, and in half of all cases attributable to infertility in the man. Although male infertility has many possible causes, it often remains unexplained. In the present study, the researchers have discovered a reason for reduced fertility in people with autoimmune polyendocrine syndrome type 1 (APS1), which increases the risk of developing autoimmune disease (caused by the immune system attacking and damaging healthy cells) and which is often used as a model for autoimmune disease in general. Infertility is common in people of both sexes with the disease. While infertility in women with APS1 is caused by autoimmune action against the ovaries, what gives rise to the corresponding infertility in men has never been ascertained. Keen to investigate whether male fertility could be explained by an autoimmune reaction against some part of the male reproductive organs, the researchers behind this new study examined the immune system of 93 men and women with APS1. “We found that the immune system in a large group of patients reacted to a protein formed only in the prostate, namely the enzyme transglutaminase 4,” says lead investigator Nils Landegren, MD, Doctoral student at Karolinska Institutet’s Department of Medicine in Solna. “What we found was that it was only men who reacted to transglutaminase 4 and that the immune reaction first appeared at the onset of puberty once the prostate gland had matured. Interestingly, previous studies on mice have shown that transglutaminase 4 plays an important part in male fertility.” Animal model for APS1 To better understand their findings, the team examined the animal model for APS1 (i.e. mice with the same genetic defect as human patients with the syndrome) and found that male mice spontaneously developed an inflammatory disease in their prostate glands – a so-called prostatitis – and reacted to transglutaminase 4. “The finds are important as they point to a new disease mechanism for male infertility, but more work needs to be done to understand the significance of autoimmune prostatitis to infertility in the male population at large,” says Dr Landegren. The researchers involved in the study were from Karolinska Institutet, SciLifeLab, Uppsala University, Stanford University and University of California San Francisco. Supervisor of the study has been Professor Olle Kämpe, MD, PhD, at the Department of Medicine, Solna, Karolinska Institutet. The study was financed with grants from the Swedish Research Council, the Torsten and Ragnar Söderberg Foundation, the Swedish Research Council Formas and the Novo Nordisk Foundation, the National Organization for Rare Disorders and the NIH. View our press release about this study Publication Transglutaminase 4 as a prostate autoantigen in male subfertility N. Landegren, D. Sharon, A. K. Shum, I. S. Khan, K. J. Fasano, Å. Hallgren, C. Kampf, E. Freyhult, B. Ardesjö-Lundgren, M. Alimohammadi, S. Rathsman, J. F. Ludvigsson, D. Lundh, R. Motrich, V. Rivero, L. Fong, A. Giwercman, J. Gustafsson, J. Perheentupa, E. S. Husebye, M. S. Anderson, M. Snyder, O. Kämpe Science Translational Medicine, Vol 7 Issue 292 292ra101 (2015), online 17 June 2015

Researchers at Karolinska Institutet have in collaboration with Spanish colleagues identified epigenetic alterations in Common Variable Immunodeficiency (CVID), the most common primary immunodeficiency, using as a starting point genetically identical monozygotic twins discordant for the disease. The findings are being published in the journal Nature Communications, and may open a door to future research avenues for the diagnosis and treatment of patients with CVID. CVID is a disorder characterized by low levels of antibodies (serum immunoglobulins) and increased susceptibility to infections. Most patients with CVID are diagnosed initially after suffering recurrent infections that involve ears, sinuses, nose, bronchi and lungs. When the lung infections are severe and occur repeatedly, can cause permanent damage to the bronchi and become chronically affected. The exact cause of low levels of serum immunoglobulins is not known. Given the heterogeneous nature of CVID, there is not a clear pattern of inheritance, although in recent years geneticists have described mutations in several genes related to the biology of lymphocytes in patients with CVID. Still, for several patients there are no identified mutations and it is thought that other mechanisms also determine the onset of the disease; in fact, there are examples of genetically identical twins, which are discordant for the manifestation of this disease. The current study was conducted in collaboration by researchers of the Chromatin and Disease Group at the Bellvitge Biomedical Research Institute (IDIBELL) and La Paz Hospital (IDIPAZ) in Spain, and the Computational Medicine team at Karolinska Institutet’s Department of Medicine, Solna. By comparing the epigenetic marks in B cells of a pair of identical twins, discordant for CVID, the researchers were able to identify the existence of epigenetic alterations in the twin with the immunodeficiency that are not present in the healthy twin. In particular, they observed higher DNA methylation levels in the twin with CVID. DNA methylation is related to the ability of cells to allow their genes to be expressed. A group of genes According to the researchers, this analysis allowed the identification of a group of genes important for the proper functioning of B lymphocytes which were more methylated in the CVID twin. Subsequently, the same genes were investigated in a cohort of individuals with CVID, and compared with a series of healthy individuals. The analysis of methylation of these genes in cells in different stages of maturation also showed that patients with CVID have partially lost the ability of demethylating those genes during the process of generating mature lymphocytes. These results indicate that patients not only produce less CVID memory B cells (the mature form which produces antibodies) but these cells are altered and have not completed properly their maturation. This work was supported by the Spanish Ministry of Economy and Competitiveness, the Fundación Ramón Areces, and the EU FP7 306000 STATegra project. This news article is an abbrivation of a press release from the IDIBELL.  Publication Monozygotic Twins Discordant for Common Variable Immunodeficiency Reveal Impaired DNA Demethylation during Naïve-to-Memory B-Cell Transition Virginia C. Rodríguez-Cortez, Lucia del Pino-Molina, Javier Rodríguez-Ubreva, Laura Ciudad, David Gómez-Cabrero, Carlos Company, José M. Urquiza, Jesper Tegnér, Carlos Rodríguez-Gallego, Eduardo López-Granados and Esteban Ballestar Nature Communications, online 17 June 2015, DOI: 10.1038/ncomms8335

New human heart muscle cells can be formed, but this mainly happens during the first ten years of life, according to a new study from Karolinska Institutet in Sweden. Other cell types, however, are replaced more quickly. The study, which is published in the journal Cell, demonstrates that the heart muscle is regenerated throughout a person’s life, supporting the idea that it is possible to stimulate the rebuilding of lost heart tissue. During a heart attack, when parts of the heart muscle are starved of oxygen, many heart cells die and are replaced by scar tissue. As this impairs functionality, many researchers are interested in the possibility of stimulating the regeneration of lost heart muscle cells. But is it possible? This is one of the big questions of regenerative medicine, and scientists have long been trying to answer it, without arriving at a consensus. To examine the regeneration of human heart cells, the team behind this new study used a combination of methods. One such was to measure the radioactive isotope C-14, exploiting the sharp rise in atmospheric levels of carbon-14 in the 1950s and 60s caused by nuclear testing. Levels then declined, which means that cells that were formed after that period give lower C-14 readings than those formed during it. Thus by measuring the amount of C-14 in a cell’s DNA, the researchers were able to calculate its age. “We examined the heart tissue from 29 deceased individuals of various ages and found that even by one month after birth, the heart contains the same number of cells as it has in adults,” says Olaf Bergmann from the Department of Cell and Molecular Biology. Cells increase in size According to the study, the heart grows during childhood because its cells increase in size rather than in number; in other words, heart cells are generated on only a modest scale, and even during a long life, only forty per cent of muscle cells are replaced. The heart also contains other types of cell, such as endothelial cells and cells in the connective tissue that go under the collective name of mesenchymal cells. What the researchers found was that these cell populations change much more than the heart muscle cells. The endothelial cells have the shortest life-cycle, and in adults all such cells are exchanged over a six-year period. The mesenchymal cells are also replaced, but more slowly – twice during a lifetime estimate the researchers behind this new study. “Our study shows that endothelial cells, mesenchymal cells and heart muscle cells are renewed in the human heart throughout life, albeit at a different rate for different cells,” says study leader Jonas Frisén from the Department of Cell and Molecular Biology. “Our findings suggest that it can be rational and realistic to develop new therapeutic strategies for strengthening the body’s own regenerative capacity to treat heart diseases.” The study was financed with grants from the Swedish Research Council, the Heart-Lung Foundation, the Swedish Cancer Society, the Tobias Foundation, StratRegen at Karolinska Institutet, the Torsten Söderberg Foundation, and the Knut and Alice Wallenberg Foundation. View our press release about this study More about the Frisén lab View a video abstract on YouTube     Publication Dynamics of cell generation and turnover in the human heart Olaf Bergmann, Sofia Zdunek, Anastasia Felker, Mehran Salehpour, Kanar Alkass, Samuel Bernard, Staffan Sjöström, Mirosława Szewczykowska, Teresa Jackowska, Cris dos Remedios, Torsten Malm, Michaela Andrä, Shira Perl, John Tisdale, Ramadan Jashari,Jens R. Nyengaard, Göran Possert, Stefan Jovinge, Henrik Druid, and Jonas Frisén Cell June 18, 2015 issue, online first 11 June  2015, DOI: http://dx.doi.org/10.1016/j.cell.2015.05.026

What might attractive career systems that promote good research look like? This was the subject of the mini-symposium on “Excellent Academic Career Systems in Europe” held at KI on 3 June. The mini-symposium on career systems arranged by KI’s Junior Faculty, an interest organisation of researchers with a PhD but as yet no professorship, and the journal Nature Genetics attracted a great deal of interest. Speakers from Europe and the US were there to talk about different solutions and experiences gained from their own countries. Stina Gerdes Barriere from the Swedish Research Council talked about how academic career paths had changed over the past 20 years, during which time the number of people working with research and education has outstripped the research appropriations. The sharpest increase has occurred in the category of junior researcher, and according to the council’s own research, career advancement for recent graduates is much slower than for previous generations; in other words, it takes those who want to continue researching longer to obtain a tenured academic position. Speakers raised the tenure-track model That Swedish academia needs clearer career paths was something on which everyone attending the symposium agreed. But what can decent career systems look like, what are they to prioritise, and at what level are they to be organised and financed? Many of the afternoon’s speakers talked on the tenure-track system, with evaluations at fixed times and permanent job offers for researchers meeting expectations. Iain Cameron from Research Councils UK talked about how universities in the UK all have different systems. Recently, a couple of universities have implemented what they term a “tenure-track equivalent” programme. Germany is also without a general career system, noted Sven Diederichs from the German Cancer Research Center DKFZ and the Institute of Pathology at Heidelberg University. Many universities operate a tenure track, but they differ from place to place. “My main point is that the most important decision is the one taken at the start when recruiting a tenure-track researcher: do we really have the resources for giving them a permanent position, and do we believe that they have the potential to become a successful, independent researcher?” said Sven Diederichs, who also spoke about the importance of having a fair, transparent and well-balanced evaluation process in place in the system. Ideas for future career systems Thomas Bjørnholm, prorector of research and innovation at Copenhagen University, shared his own experiences of implementing a tenure-track system. The model is inspired by California’s Berkeley University and has brought about considerable changes in organisation and in attitudes to Copenhagen University. The positions are for six years, with evaluations after five. Six-year positions were also something that both the Junior Faculty and Dean of Research Hans-Gustaf Ljunggren saw as interesting alternatives when talking about their different ideas about what a future career system at KI might look like. After the presentations, the speakers engaged in a panel debate with representatives of the Young Academy of Sweden and the National Junior Faculty of Sweden on the difficulties of assessing a researcher’s potential so early as directly after a postdoc period. Interviews were mentioned as a way of obtaining some idea of a researcher’s independence. The applicant’s publication history and research programme were other criteria that the panel deemed important. There was also general agreement that the evaluation criteria had to be clearly defined from the start. Text: Karin Söderlund Leifler  

A team of Swedish researchers finds that early cardiopulmonary resuscitation more than doubles the chance of survival for patients suffering out-of-hospital cardiac arrest. The percentage of patients who receive life-saving resuscitation has also increased substantially thanks to so-called SMS Lifesavers. These results are published simultaneously in two studies in the highly reputed New England Journal of Medicine. The two studies were conducted by researchers at the Center for Resuscitation Science at Karolinska Institutet and Södersjukhuset (Stockholm South General Hospital) in collaboration with University of Borås, Danderyd Hospital and Sahlgrenska Academy, all in Sweden. “Both these studies clearly show that cardiopulmonary resuscitation is an effective, life-saving treatment, and that further encouragement must be given to respond swiftly on suspected cardiac arrest,” says Dr Jacob Hollenberg, Cardiologist and Head of Research at the Center for Resuscitation Science. In one of the two articles, the researchers have analysed over 30,000 cases of out-of-hospital cardiac arrest in Sweden. The results show that cardiopulmonary resuscitation performed before the arrival of the ambulance is associated with over a two-fold increase in the chance of survival. This powerful effect is independent of age, sex, place, cause, ECG pattern, and time period. According to the researchers, this study unique in several ways. Aside from its main results, is the number of cases analysed, the fact that data is reproducible for three decades and that the material was subjected to thorough correction for sources of error and bias. Dispatching CPR trained volunteers In the other article, the researchers have evaluated a new method of dispatching CPR trained volunteers, known as SMS Lifesavers to cardiac arrests. Their results show that these volunteers have caused a 30 % increase in the number of patients who receive cardiopulmonary resuscitation before the arrival of paramedics, the rescue services or the police. The study involved 10,000 civilian volunteers in Stockholm County who were alerted by mobile phone text message to the cardiac arrest in order to administer cardiopulmonary resuscitation if they were within a range of 500 metres. “Traditional methods such as mass public training, which are now used throughout the world, are important but have not shown any evidence of a similar increase,” says Dr Hollenberg. “The new mobile phone text-message alert system shows convincingly that new technology can be used to ensure that more people receive life-saving treatment as they wait for an ambulance.” This research was financed by grants from the Heart-Lung Foundation, Stockholm County Council, the Swedish Association of Local Authorities and Regions and the Laerdal Foundation for Acute Medicine in Norway. Facts about cardiac arrest: About 10,000 Swedes suffer out-of-hospital cardiac arrest every year. In the USA, more than 300 000 persons suffer out-of-hospital cardiac arrest each year. Only 1 in 10 victims survive. Cardiac arrest is often caused by acute myocardial infarction. The delay between onset and treatment in the form of cardiopulmonary resuscitation and defibrillation is decisive for survival. More than 3 Million Swedes (out of a population of 10 Million inhabitants) have been trained in CPR. More about SMS Lifesavers Our press release about this research Publications Early Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest Ingela Hasselqvist-Ax, Gabriel Riva, Johan Herlitz, Marten Rosenqvist, Jacob Hollenberg, Per Nordberg, Mattias Ringh, Martin Jonsson, Christer Axelsson, Jonny Lindqvist, Thomas Karlsson, and Leif Svensson NEJM 2015; 372:2307-15, online 11 June 2015 Mobile-Phone Dispatch of Laypersons for CPR in Out-of- Hospital Cardiac Arrest Mattias Ringh, Mårten Rosenqvist, Jacob Hollenberg, Martin Jonsson, David Fredman, Per Nordberg, Hans Järnbert-Pettersson, Ingela Hasselqvist-Ax, Gabriel Riva, and Leif Svensson NEJM 2015; 372:2316-25, online 11 June 2015

A new multinational study of parental age and autism risk, published in the journal Molecular Psychiatry, found increased autism rates among children whose parents have relatively large gaps between their ages. The study also confirmed that older parents are at higher risk of having children with autism. The analysis, which is the largest-ever, included more than 5.7 million children in five countries. The study builds on the broader research of the International Collaboration for Autism Registry for Epidemiology (iCARE). The investigators looked at autism rates among 5,766,794 children – including more than 30,000 with autism – in Denmark, Israel, Norway, Sweden and Western Australia. The children were born between 1985 and 2004, and the researchers followed up on their development between 2004 and 2009, checking national health records for autism diagnosis. “By combining information across five countries, we have created a valuable base for research into autism”, says Christina Hultman, a Professor of Psychiatric Epidemiology at Karolinska Institutet and one of the initiators of the iCare collaboration. Previous studies have found links between parental age and increased risk of autism in children. However, many questions still remain. The goal of this new study was to determine whether advancing maternal or paternal ages independently increase autism risk – and to what extent each might do so. Researchers identified and controlled for other age-related influences that might affect autism risk. When separating the influence of mother’s versus father’s age, they also adjusted for the potential influence of the other parent’s age. “After finding that paternal age, maternal age and parental-age gaps all influence autism risk independently, we calculated which aspect was most important,” says Dr Sven Sandin,a statistician and epidemiologist at Karolinska Institutet, also affiliated to the Icahn School of Medicine at Mount Sinai in New York, US. “It turned out to be parental age, though age gaps also contribute significantly.”  Key findings: Autism rates were 66 percent higher among children born to dads over 50 years of age than among those born to dads in their 20s. Autism rates were 28 percent higher when dads were in their 40s versus 20s. Autism rates were 15 percent higher in children born to mothers in their 40s, compared to those born to moms in their 20s. Autism rates were 18 percent higher among children born to teen moms than among those born to moms in their 20s. Autism rates rose still higher when both parents were older, in line with what one would expect if each parent’s age contributed to risk. Autism rates also rose with widening gaps between two parents’ ages. These rates were highest when dads were between 35 and 44 and their partners were 10 or more years younger. Conversely, rates were high when moms were in their 30s and their partners were 10 or more years younger. The higher risk associated with fathers over 50 is consistent with the idea that genetic mutations in sperm increase with a man’s age and that these mutations can contribute to the development of autism spectrum disorders (ASD). By contrast, the risk factors associated with a mother’s age remain unexplained, as do those associated with a wide gap between a mother and father’s age. “These results suggest that multiple mechanisms are contributing to the association between parental age and ASD risk”, says Sven Sandin. “However, it is important to remember that the majority of children born to older or younger parents will develop normally.” Christina Hultman and Sven Sandin are both affiliated to the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. The study was funded Autism Speaks, which is the world’s leading autism science and advocacy organization. This news article is an edited version of a press release from Autism Speaks. Publication Autism risk associated with parental age and with increasing difference in age between the parents Sandin Sven, Schendel Diana, Magnusson Patrik, Hultman Christina, Surén Pål, Susser Ezra, Grønborg Therese, Gissler Mika, Gunnes Nina, Gross Raz, Henning Maria, Bresnahan Micki, Sourander Andre, Hornig Mady, Carter Kim, Francis Richard, Parner Erik, Leonard Helen, Rosanoff Michael, Stoltenberg Camilla, Reichenberg Abraham Molecular Psychiatry (2015) 1359-4184/15, online 9 June 2015

Karolinska Institutet and Max Planck Society, Germany, have signed an agreement on a new joint research laboratory at Karolinska Institutet specialising in congenital metabolic diseases. The new Max Planck Institute for Biology of Ageing – Karolinska Institutet Laboratory is to be established in the Department of Laboratory medicine on Karolinska Institutet’s Solna campus, and will deepen existing research into congenital metabolic diseases. “This initiative is part of Karolinska Institutet’s strategy to tie itself more closely to internationally leading research institutes,” says Karolinska Institutet vice-chancellor, Anders Hamsten. At the Max Planck Institute in Cologne (the partner organisation) this research has, to date, mostly been done using animal models, and a new laboratory at Karolinska Institutet will offer fresh opportunities to collaborate using, amongst other resources, the unique patient material to which Karolinska Institutet’s leading scientists have access. “Even if we’ll be collaborating on a small scale at first, it’s important to both parties,” says Hans-Gustaf Ljunggren, dean of research at Karolinska Institutet. “Together, we’ll advance our research in a way that would have been impossible had we been working alone.” The collaborative programme is due to commence in 2015, and will run for five years under a common research group leader and with researchers recruited from Karolinska Institutet in Stockholm and visiting researchers from the Max Planck Institute in Cologne. There is also provision in the programme for doctoral students and postdocs to join as visiting researchers in both cities. Karolinska Institutet and the Max Planck Institute are investing the equivalent of 8.5 million kronor each in the programme.