KI News

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

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

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

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

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

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

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

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

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

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

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

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

Every academic year, around 1,600 students are educated in anatomy at Karolinska Institutet. These students are now able to access a visualization table on which they can turn, rotate and make incisions into digital patients. This new tool is not a replacement for donated bodies, but is a valuable complement to them.  Karolinska Institutet has invested in an interactive visualization table in order to further develop its teaching of anatomy. The table provides students with the opportunity to conduct virtual examinations of  three-dimensional patients. The visualization table is becoming an important complement to anatomy teaching using donated bodies in the medicine and dentistry programmes. The table will also be used in other study programmes that include courses in anatomy. Anatomy teaching in these courses has previously been based mainly on pictures and plastic models, which means that the visualization table marks a significant educational improvement. "The visualization table is an important investment in the modernisation and improvement of the quality of our teaching", says Sandra Ceccatelli, Head of the Department of Neuroscience, which is responsible for anatomy education at KI. "This instrument unlocks unique opportunities to convey fundamental knowledge of the body, involving an entirely new way to teach our students anatomy. We also believe that the visualization table may become a very exciting research tool in the future." The visualization table, produced by Sectra, is a Swedish innovation that has garnered much international attention. It can be described, most simply, as a very large touch-screen – 55 inches – that allows the user to study three-dimensional images of scanned human bodies interactively. Using simple finger movement, the user can rotate the body, make incisions, zoom in and out, peel back layers, etc. The source images come from magnetic resonance imaging and computed tomography of real human bodies. "The visualization table can be likened to a huge tablet computer and is controlled using similar gestures, which makes it very intuitive and easy to use", says Professor Björn Meister, Departmental Educational Coordinator for Anatomy and Histology. "Studying a real body is the best way to learn anatomy. Previously, only medical and dental students have had this opportunity, but now all students studying anatomy are afforded this opportunity." The visualization table is intended to be used as part of all KI's study programmes that include courses in anatomy: medicine, dentistry, biomedicine, physiotherapy, psychology, dental hygiene, optometry, speech therapy, and midwifery. This involves a total of around 1,600 students per year. The table has already begun to be used on a small-scale and the plan is for it to be integrated into teaching at the start of the autumn semester. Björn Meister believes the table has many educational benefits. "The interactivity is obviously an important component, as is the fact that it uses 3D images. It is hard to gain a three-dimensional understanding of some parts of the human body just from looking at two-dimensional images. The ability to show and hide different layers, for example removing the muscles and nerves, is obviously very useful", says Björn Meister. "Another important aspect is the ability to study many bodies instead of just one. All bodies are different, and this allows is to demonstrate this diversity to our students. Another advantage compared to real bodies is the ability to repeat examinations. The digital patient material is not consumed, and can be re-used any number of times." In the long-term, Meister can also see interesting opportunities to use the table in research at KI. "One idea which has already come up is to use the table to study microscopic materials", he says. "Exciting microscopy techniques that provide three-dimensional data have been developed and the table would be a very good way of visualising these." Sectra's education portal allows KI to access materials from other higher education institutions with visualization tables around the world. Björn Meister hopes that KI and Karolinska University Hospital will also be able to contribute to this database in the future with their own patient cases.   Text: Anders Nilsson Photo: Stefan Zimmerman

Alcohol and drug misuse are responsible for around a third of all deaths in former male prisoners and half in female ex-prisoners, according to a new study of almost 48000 ex-prisoners from Karolinska Institutet and University of Oxford. The study, which is being published in the published The Lancet Psychiatry, also shows that a substantial proportion of these deaths are from preventable causes, such as accidents and suicide. Several studies have reported high death rates after release from prison, but few have looked at potential risk factors for these high rates. In the current study, investigators examined deaths in all individuals released from prison in Sweden between 1th January 2000 and 31th December 2009, in total 47326 prisoners. The causes of death were assessed and compared with imprisoned siblings without substance use disorder (alcohol and illicit drug use) and other psychiatric disorders, to isolate the impact of the illnesses from the prison setting. The researchers then estimated the proportion of deaths that could be attributed to alcohol and substance abuse and other psychiatric disorders (i.e. schizophrenia, ADHD, depression), by calculating the population attributable fractions (PAF) the proportion of deaths that can be attributed to each risk factor. The results show that roughly 6% (2874) of prisoners died after release, during an average follow-up of 5 years. 1276 deaths (44%) were due to potentially preventable external causes, accounting for roughly 3% of all external cause mortality in Sweden between 2000 and 2009. The researchers found a particularly high risk of death for prisoners with a history of drug and alcohol misuse following release from prison that persisted for years afterwards rather than just weeks as previously thought. Related to alcohol and substance use Around a third (34%) of all deaths in men and half (50%) in women released from prison were related to alcohol and substance use, even after accounting for the influence of socio-demographic, criminological, and familial (genetic and environmental) factors. Alcohol and substance abuse accounted for 42% of deaths from external causes in male ex-prisoners and 70% in female ex-prisoners. In contrast to previous research, the investigators found no evidence that other psychiatric disorders increased the post-release death rate. The authors point out that although Sweden has a relatively low incarceration rate, the prevalence of substance abuse and severe psychiatric disorders reported in this study are similar to the UK, USA, and other high-income countries. Study leader was Seena Fazel, Professor of Forensic Psychiatry at the University of Oxford, and first-study author was Zheng Chang, a Postdoc at the Department of Department of Medical Epidemiology and Biostatistics at Karolinska Institutet. Funding bodies has been The Wellcome Trust, the Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare. This news article is an abbreviation of a press release issued by the Lancet Psychiatry. Publication Substance use disorders, psychiatric disorders, and mortality after release from prison: a nationwide longitudinal cohort study Zheng Chang, Paul Lichtenstein, Henrik Larsson, Seena Fazel The Lancet Psychiatry, online 22 April 2015, doi: http://dx.doi.org/10.1016/S2215-0366(15)00088-7

Maria Masucci, professor of virology at Karolinska Institutet’s Department of Cell and Molecular Biology, has been appointed Deputy Vice-Chancellor for International Affairs. The position includes overall responsibility for KI's international issues, specifically the university’s long-term alliances with world-leading universities and research institutes. “Our aim is to strengthen our position as an internationally leading university by engaging in international partnerships on research and education at all academic levels,” says Karolinska Institutet’s vice-chancellor, Anders Hamsten. “Maria Masucci is now in charge of the further development of our internationalisation strategy.” Shortly after graduating as a doctor from Ferrara University in Italy in 1977, Maria Masucci came to Karolinska Institutet, where she has been studying and working ever since. Her research has focused on different aspects of tumour biology, especially infection and cancer and the interaction of tumor viruses with their targets cells and infected hosts. Apart from her research at Karolinska Institutet, Maria Masucci has held a professorship at Lund University and been a visiting researcher at MIT and Harvard in Boston (USA), the University of Birmingham (England) and the Netherland Cancer Institute in Amsterdam (Netherlands). She also has research contacts in Italy, Germany and China. “It’s a fantastic, exciting honour to be given this appointment,” she says. “Karolinska Institutet is already engaged in important international partnerships, but we need to create more long-term alliances with leading international universities and research institutes. Doing this will enable Sweden and Karolinska Institutet to raise the quality of their education and research, and to translate results into innovations and new therapies more quickly.” The new office of Deputy Vice Chancellor for International Affairs will bolster the university management, and is one of the important offices for the implementation of Karolinska Institutet’s Strategy 2018.

Karolinska Institutet’s vice-chancellor has announced his decision on one of the two allegations of scientific misconduct against professor Paolo Macchiarini. The decision, for which the vice-chancellor requested a pronouncement from KI’s Ethics Council, was one of acquittal. It was in June 2014 that Professor Pierre Delaere filed a report on suspected scientific misconduct against Paolo Macchiarini and his work in the field of regenerative medicine. The Higher Education Ordinance stipulates that a university must investigate suspected scientific misconduct should it receive a report of such. According to Karolinska Institutet’s regulations, it is the duty of the vice-chancellor to investigate a report of this kind and decide on it either by passing it on without further action, or, if misconduct is confirmed, by taking appropriate action. In light of the information given in Professor Pierre Delaere’s letter and the statement of opinion issued by the Ethics Council, Karolinska Institutet does not find Professor Paolo Macchiarini guilty of scientific misconduct. Another case of scientific misconduct involving Professor Macchiarini is currently under investigation. Behind these allegations is Karl-Henrik Grinnemo and three other doctors, who have submitted a substantial amount of material. In this case, the vice-chancellor has asked an external expert to issue a statement of opinion. A decision on the matter is expected before the summer. In yet another case, the Ethics Council has been asked by the vice-chancellor to issue a statement on a report against Karl-Henrik Grinnemo concerning scientific misconduct in conncection with a grant application. The report against him was filed by a colleague of Paolo Macchiarini’s. The Ethics Council’s pronouncement on the matter is expected in the coming few weeks. Science Magazine: Artificial trachea pioneer cleared in first of two misconduct cases

The threat of punishment combined with people’s willingness to copy others – this is the basis for a new psychological model that can describe how traditions and norms are created and maintained according to researchers at Karolinska Institutet's Emotion Lab in a study published in the Journal of Experimental Psychology: General. Scientists have shown that animals learn from each other through social learning when there is approaching danger. For example, information about an imminent predator spreads through a flock of birds which then collectively reacts and flees. Yet, the role of social learning in avoiding danger has not been studied specifically in humans. “We wanted to find out how these situations function in humans when we need to avoid danger. We discovered that two separate, simple, psychological mechanisms – the copying of others behaviour and the rewarding properties  of avoiding danger together forms a potent driving force that helps explain how we can create and maintain norms and traditions,” says Björn Lindström, researcher at the Department of Clinical Neuroscience. Along with research leader Andreas Olsson, he conducted four experiments that included 120 test subjects. In the first experiment, the study participants were asked to choose between two pictures, A and B, on a screen 20 times. They were told that an unpleasant electric shock (which they had felt beforehand) would be given if they made the wrong choice. In reality, however, no electric shocks were given for any answer. Before making their choice, the subjects were shown a video clip of another person faced with the same choice, without being shown the consequence of the decision. The person in the video choose picture A each time. And so did the subjects in more than 95 percent of their choices. When the subjects were instead promised a reward – a chance to win movie tickets – they adhered to the video person's example in only 60 percent of the cases. In an experiment where there was the threat of an arbitrary punishment, adherence to the example in the video dropped to below 70 percent. “Our conclusion is that when we are promised a reward, we are more inclined to break the pattern, and social learning tends to play a smaller role. But when it comes to avoiding danger, social learning has a powerful influence on our behaviour when it is proved to yield good results. But in cases where social learning is shown not offer effective protection from danger, we are also more inclined to break the pattern,” says Andreas Olsson, docent and research team leader at the Department of Clinical Neuroscience at Karolinska Institutet. In the fourth study, the researchers wanted to find out whether the inclination to choose only option A could be passed down from one person to the next, under the perceived threat of an electric shock. Ten subjects were separately shown the video in which the person choose option A and were asked to make their choice. Ten new test subjects were then shown video of the choice made by one of the first test subjects, without knowing what the consequence would be. When five generations of test subjects had made their choices after watching someone from the previous generation make their choice, picture A remained the chosen alternative in 95 percent of answers. These mechanisms might help to explain how certain arbitrary traditions can be created and maintained, such as taboos about clothes or forms of behaviour which have no real significance to the group or individual. In this case we created a "choose option A" tradition which remained strong after five generations. Arbitrarily prohibiting certain types of food, for example, that do not need to be avoided for any particular reason, could be maintained because the individuals in the group will tend to fear the disapproval of their group peers if they ate the forbidden food,” says Björn Lindström. The study was funded by the Swedish Research Council and the European Research Council (ERC 284366, ELSI) Publikation: ”Mechanisms of Social Avoidance Learning Can Explain the Emergence of Adaptive and Arbitrary Behavioral Traditions in Humans”. Björn Lindström och Andreas Olsson. Journal of Experimental Psychology: General, online 13 April 2015, doi: 10.1037/xge0000071 Read more about Andreas Olsson's research team at Karolinska Institutet at: www.emotionlab.se

New research from Karolinska Institutet in collaboration with Oxford University shows that close relatives of men convicted of sexual offences commit similar offences themselves more frequently than comparison subjects. This is due to genetic factors rather than shared family environment. The study includes all men convicted of sex crime in Sweden during 37 years. “Importantly, this does not imply that sons or brothers of sex offenders inevitably become offenders too”, says Niklas Långström, Professor of Psychiatric Epidemiology at Karolinska Institutet and the study’s lead author. “But although sex crime convictions are relatively few overall, our study shows that the family risk increase is substantial. Preventive treatment for families at risk could possibly reduce the number of future victims.” The report is published in the International Journal of Epidemiology and based on anonymised data from the nationwide Swedish crime and multigeneration registers.The research included all 21,566 men convicted for sex offences in Sweden between 1973 and 2009, for example rape of an adult (6,131 offenders) and child molestation (4,465 offenders). The researchers looked at the share of sex crimes perpetrated by fathers and brothers of convicted male sex offenders and compared this to the proportion among comparison men from the general population with similar age and family relationships. Familial clustering of sex offenders The results suggested familial clustering of sex offenders, about 2.5 percent of brothers or sons of convicted sex crime offenders are themselves convicted for sex crimes. The equivalent figure for men in the general population is about 0.5 percent. Using a well-established statistical calculation model, the researchers also analysed the importance of genetic and environmental factors for the risk of being convicted of sexual abuse. “We found that sex crimes mainly depended on genetic factors and environmental factors that family members do not share with one another, corresponding to about 40 percent and 58 percent, respectively”, says Niklas Långström. “Such factors could include emotional lability and aggression, pro-criminal thinking, deviant sexual preferences and preoccupation with sex.” Self-reported sexual victimization rates in Sweden are largely similar to those in other Western and central European nations, Canada and the USA.  Other cross-national comparisons of police-reported offences should be done cautiously because of differences in legal definitions, methods of offence counting and recording, and low and varying reporting rates of sexual violence to the police. The research was funded by the Swedish Prison and Probation Service R&D, the Swedish Research Council, the Wellcome Trust and the CIHR Banting fellowship program. Niklas Långström is also the national scientific advisor for the Swedish Prison and Probation Service. Find our press release about this research Publication Sexual offending runs in families: A 37-year nationwide study Niklas Långström, Kelly M. Babchishin, Seena Fazel, Paul Lichtenstein & Thomas Frisell International Journal of Epidemiology, online 9 April 2015

A new study led by researchers at Sweden’s Karolinska Institutet and Nanyang Technological University in Singapore, provides experimental evidence that a drug that inhibits the EphB-signalling pathway in the cell effectively can suppress the development of intestinal tumours. According to the investigators, this knowledge may be important in the design of new treatments for abrogating adenoma formation and cancer progression in patients predisposed to develop colorectal cancer. Colorectal cancer is one of the three most common cancers worldwide and almost 95 percent of colorectal cancers are adenocarcinimas. In the current study, being published in the journal Science Translational Medicine, the international interdisciplinary research team demonstrates that the drug Imatinib, a tyrosine kinase inhibitor widely used to treat leukemia, can inhibit adenoma initiation and growth in the intestine through a signalling pathway related to a group of cell receptors called EphB. The investigators reached this conclusion by treating different groups of mice, genetically engineered to develop intestinal adenomas of varying severity with Imatinib and comparing them with untreated control. Imatinib was able to block adenoma initiation, at the stem cell level, by around 50 percent which significantly reduced tumour growth and proliferation. Human colonic tumour explants from patients were subsequently used to confirm this effect of Imatinib. Specifically inhibited “Using Imatinib, we have shown that the EphB-signalling pathway is specifically inhibited which results in reduced intestinal tumour initiation and growth”, said Dr. Parag Kundu at Nanyang Technological University, first author of the study. The team could also show interesting long term effects in which Imatinib increased the life span of a mouse model that mimics human colon cancer. Interestingly, the drug was also effective in increasing the survival of mice with late-stage adenomas and rectal bleeding. According to the investigators, these findings suggest that short term intermittent chemotherapies would also be possible to consider as a treatment model. Such an approach would substantially reduce the side effects known to occur when Imantinib have been given for longer periods. “Our findings provide experimental evidence that Imatinib treatment did not interfere with the tumour suppressor function of EphB receptors”, said Jonas Frisén, Professor of Stem Cell Research at Karolinska Institutet, who supervised the study.” Clinical implications “Our work may have important clinical implications, as Imatinib is a potentially novel drug for the treatment of adenoma formation and cancer progression in patients predisposed to develop colorectal cancer”, commented co-author Sven Pettersson, Professor of Host-Microbe Interactions at Karolinska Institutet, and at the Lee Kong Chain School of Medicine at Nanyang Technological University. This research was supported by grants from the Swedish Research Council, the Swedish Cancer Society, Karolinska Institutet, the Tobias Foundation, the Knut and Alice Wallenberg Foundation, the Torsten Söderberg Foundation, Singapore Millennium Foundation, and the LKC School of Medicine at NTU of Singapore. Find our press release about this research Publication An EphB Abl signaling pathway is associated with intestinal tumor initiation and growth P. Kundu, M. Genander, K. Strååt, J. Classon, R. A. Ridgway, E. H. Tan, J. Björk, A. Martling, J. van Es, O. J. Sansom, H. Clevers, S. Pettersson, J. Frisén Science Translational Medicine, online 1 April 2015, Vol. 7 Issue 281, doi: 10.1126/scitranslmed.3010567

With relatively simple measures which reach the poorest families, life-saving traditions during pregnancy, delivery and the newborn period can be improved in Uganda, according to a randomized study which was conducted in collaboration with Karolinska Institutet and Makerere University in Uganda. The results have been reported in a special issue of the peer-reviewed journal Global Health Action. Child mortality rates in Uganda are declining. However, the improvements are slower in terms of deaths occurring among newborns and stillbirths. A large share of these deaths can be prevented. In the Uganda Newborn Study, researchers investigated the effect of a care package which linked families, community health workers and health facilities in rural areas in Uganda. In half of the villages volunteers from the village were trained. They conducted two consultative home visits among pregnant women before delivery and three visits during the first week following delivery.  Researchers found that behaviours which reduce mortality during the newborn period could be strengthened by this interaction.  Breastfeeding practices, skin-to-skin care immediately after birth, delaying a baby’s first bath, and hygienic care of the baby’s umbilical cord stump were higher amongst the group of women receiving home visits compared to the control group. The study, which was initiated by Harriet Wallberg, former Vice-Chancellor of Karolinska Institutet during her Uganda visit has contributed to building research capacity in the country. Till now it has resulted in two dissertations in collaboration between Karolinska Institutet and Makerere University. The study’s results and material now comprise the Uganda Ministry of Health’s guidelines in the area.  Stefan Peterson, who is associated with the Department of Public Health Sciences at Karolinska Institutet, Uppsala University and Makerere University, is one of the researchers in charge of the study:  “We are especially happy to have graduated two Ugandan PhDs from this study who are experts in newborn health research.  Capacity development should be part of all studies and that is how we will build national cadres of researchers,” he says in an international press release from the journal. The authors of the articles include Mariam Claeson from the Bill and Melinda Gates Foundation, who was appointed as Honorary Doctor of Medicine at Karolinska Institutet in 2015, and Peter Waiswa, who is a researcher at Makerere University and Karolinska Institutet. The research was funded by the collaboration supported by the Swedish International Development Cooperation Agency, Sida, between both universities as well as Save the Children through a grant from the Bill and Melinda Gates Foundation and its blog also discusses the study.   The journal Global Health Action is based in Umeå and the special issue Newborn health in Uganda contains nine scientific articles related to the Uganda Newborn Study, and has open access.   How to Bend the Curve on Newborn Mortality – Key Learnings from Uganda   Text: Karin Söderlund Leifler