Integrative Molecular Phenotyping

KI News

Updated: 1 hour 9 min ago

Oral contraceptives linked to reduced risk of rheumatoid arthritis

Fri, 18/08/2017 - 10:12
Taking oral contraceptives is associated with a lowered risk of developing rheumatoid arthritis, finds a new observational study by researchers at Karolinska Institutet published in Annals of the Rheumatic Diseases. But no significant link was found for breastfeeding after accounting for various potentially influential factors. The researchers analysed data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) to find out if there is a link between the development of rheumatoid arthritis and use of oral contraceptives and/or breastfeeding among adult women who had had at least one child. The study included women aged 18 and above, living in defined areas of Sweden between 1996 and 2014. During this timeframe, 2809 women were diagnosed with rheumatoid arthritis. 5312 women randomly selected from the general population and matched for age acted as a control group. Significantly reduced risk The women were asked about their contraceptive and reproductive histories, their lifestyle, their education and whether they had breastfed their children. In addition, blood samples were taken to check for ACPA (anti-citrullinated protein) antibodies. Nine out of 10 people who test positive for ACPA antibodies will have rheumatoid arthritis, and the presence of these antibodies may indicate more serious disease. The risk of developing ACPA-positive rheumatoid arthritis was 15 per cent lower in current users of oral contraceptives and 13 per cent lower in past users compared with women who had never used an oral contraceptive. Using the Pill for more than seven years was associated with a 19 per cent lower risk of developing both ACPA-positive and ACPA-negative rheumatoid arthritis. However, no firm conclusions can be drawn about cause and effect in an observational study, and the researchers lacked information about the dose or type of oral contraceptive. Breastfeeding did not have the same effect Although a lower risk was also found among women who had breastfed at least one child, this was not significant after having accounted for potentially influential factors. The study was carried out by Cecilia Orellana at the Department of Clinical Neuroscience and Camilla Bengtsson at the Institute of Environmental Medicine, Karolinska Institutet, among others. The research was supported by grants from the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, King Gustav V’s 80-year foundation, Vinnova, the Swedish Foundation for Strategic Research, the Swedish Rheumatic Foundation, the Stockholm County Council, the Insurance Company AFA, the Innovative Medicines Initiative-supported BTCure project, and the National Institutes of Health. This news article is based on a press release from Annals of the Rheumatic Diseases. Publication Cecilia Orellana, Saedis Saevarsdottir, Lars Klareskog, Elizabeth W. Karlson, Lars Alfredsson and Camilla Bengtsson. “Oral contraceptives, breastfeeding and the risk of developing rheumatoid arthritis: results from the Swedish EIRA study”. Annals of the Rheumatic Diseases, online 17 August 2017. doi 10.1136/annrheumdis-2017-211620

Killing bacteria by hacking plastics with silver and electricity

Mon, 14/08/2017 - 10:48
Researchers at the Swedish Medical Nanoscience Center at Karolinska Institutet have developed an innovative way of hacking conducting plastics so as to prevent bacterial growth using silver nanoparticles and a small electrical current. The method, which could prove to be useful in preventing bacterial infections in hospitals, is presented in the scientific journal Advanced Healthcare Materials. Hospital wards are full of plastic surfaces, plastic tubes and plastic devices, each one potentially harbouring dangerous microbes. Bacteria are capable of surviving for a long time on plastic surfaces, from which they can spread to patients and cause infections. Effective combination of small attacks While both large electrical currents and high silver concentrations are known to kill bacteria, they also pose a risk to humans, which is why their use in hospitals is limited. New research lead by Professor Agneta Richter-Dahlfors at Karolinska Institutet’s Department of Neuroscience shows that it is not necessary to use dangerous concentrations of silver or large currents in order to kill bacteria, if these are used in combination. “By targeting the bacteria on several fronts at the same time, the effect of different small attacks becomes larger than when each factor is acting on its own”, explains Agneta Richter-Dahlfors. The research team focussed on the notorious hospital pathogen Staphylococcus aureus. They found that applying tiny electrical currents to a conducting plastic surface had no effect on bacterial growth. On a similar surface exposing an attached layer of silver nanoparticles, bacterial growth was reduced. However, application of a tiny electrical current to the latter surface enhanced the effect of attached silver nanoparticles, and the bacteria were completely destroyed. Electrical fields weaken bacterial cells “It’s a phenomenon known as the bioelectric effect, whereby electrical fields weaken bacterial cells against external attacks”, says PhD student Salvador Gomez-Carretero at Karolinska Institutet's Department of Neuroscience. “We use electrical signals to increase the antimicrobial activity of the silver nanoparticles. This reduces the amount of silver needed, which is beneficial for both the patient and the environment.” In the future, the researchers hope that this technology will help to keep surfaces in hospitals and other settings requiring high hygienic standards free from bacteria that can cause life-threatening infections. “It has not yet been tested in the clinic, but we believe this technology could be a good approach to limiting the spread of infectious bacteria and the incidence of hospital-acquired infections” says Professor Richter-Dahlfors. The study was financed by the Swedish Research Council, Vinnova, Carl Bennet AB and the Swedish Medical Nanoscience Center. Publication Salvador Gomez-Carretero, Rolf Nybom and Agneta Richter-Dahlfors. Electroenhanced Antimicrobial Coating Based on Conjugated Polymers with Covalently Coupled Silver Nanoparticles Prevents Staphylococcus aureus Biofilm Formation. Advanced Healthcare Materials, online 14 August 2017. doi: 10.1002/adhm.201700435.

Karolinska Institutet number one in Sweden in innovation ranking

Fri, 11/08/2017 - 11:38
Karolinska Institutet (KI) is ranked 38 of 200 in the science magazine Nature's innovation ranking, Nature Index 2017 Innovation, which measures how companies and organizations use the university's research results. KI is the highest ranking Swedish university and the only one to enter the top 50. The Nature Index Innovation report is based on how often research from academia and other public research institutions is cited in patents owned by non-academic organizations, for example companies in the IT, pharmaceutical and biomedical industries.  "While one should bhe cautious about drawing far-reaching conclusions from rankings, this is an important indication of how KI stands in relation to other universities and a confirmation that we conduct high-quality research that is relevant to society at large,” says Ole Petter Ottersen, Vice-Chancellor at KI who took office on August 1. To enter Nature Index Innovation, a university must have many publications in high-ranking scientific journals, and research findings that are applicable and cited in patents. "This ranking provides a very interesting way to determine how university research contributes to the development of products of benefit to our society. It measures how third parties use our research findings to develop quality products and services," says Richard Cowburn, responsible for business collaboration at Karolinska Institutet. USA in the top American universities fill 38 of the top 50 spots in the Nature Index 2017 rankings; among the top five are Scripps Research Institute, San Diego, followed by Rockefeller University, New York; Massachusetts Institute of Technology, Boston; University of Massachusetts Medical School, Worcester and The University of Texas Southwestern Medical Center, Dallas. KI is one of six European universities in the top 50. Other Swedish universities appearing in the list are Uppsala University and Stockholm University. Nature Index Innovation bases its ranking on Lens, which is an open web-based tool that measures research's impact on innovations.

New insight into how immune cells are formed

Thu, 10/08/2017 - 13:14
In contrast to what has been previously believed, development of blood stem cells to mast cells, a type of specialised immune cell, does not depend on a growth factor called stem cell factor. This has been demonstrated in a new collaborative study by researchers at Karolinska Institutet and Uppsala University, and published in the scientific journal Blood. The results could pave the way for new treatments for certain types of blood diseases. Allergy and asthma affect a high percentage of the population. Mast cells are specialised immune cells that play an important role not only in these conditions but also in other diseases such as mastocytosis, a haematologic disease involving an increased number of mast cells. It has been commonly understood that the growth factor stem cell factor, which stimulates mast cell development, is essential for the formation of mast cells. Now researchers at Karolinska Institutet and Uppsala University have shown that this is not the case. The researchers analysed mast cells and their progenitors in blood from patients with chronic myeloid leukaemia, a disease of the blood. “When the patients were treated with the drug imatinib (Glivec), which blocks the effect of stem cell factor, the number of mature mast cells dropped, while the number of progenitor cells did not change. We were thus able to conclude that mast cell progenitors did not require stem cell factor”, says Professor Gunnar Nilsson at the Department of Medicine, Solna, and the Centre of Excellence for Systemic Mastocytosis at Karolinska Institutet, and Visiting Professor at the Department of Medical Sciences, Uppsala University, who led the study. Could lead to new treatments By culturing the mast cell progenitor cells present in blood, which are relatively uncommon (about 10 cells per million white blood cells), the researchers found that mast cell progenitors could survive, divide and partially mature without stem cell factor. Instead, development can take place with the factors interleukin 3 and 6. “The study increases our understanding of how mast cells are formed and could be important in the development of new therapies, for example for mastocytosis for which treatment with imatinib/Glivec is not effective. One hypothesis that we will now test is whether interleukin 3 can be a new target in the treatment of mast cell-driven diseases”, comments Joakim Dahlin, Researcher at the Department of Medicine, Solna, at Karolinska Institutet and first author of the study. The research has been financed with support from the Swedish Research Council, the Swedish Cancer Society, Ollie and Elof Ericsson’s Foundation, Hans von Kantzow’s Foundation, Tore Nilson’s Foundation, the Cancer and Allergy Foundation, The Cancer Research Funds of Radiumhemmet and Karolinska Institutet. Publication Joakim S Dahlin, Maria Ekoff, Jennine Grootens, Liza Löf, Rose-Marie Amini, Hans Hagberg, Johanna S Ungerstedt, Ulla Olsson-Strömberg, Gunnar Nilsson. KIT signaling is dispensable for human mast cell progenitor development. Blood, online 8 August 2017. doi: 10.1182/blood-2017-03-773374.

Method developed that gives researchers better conditions for studying insulin-producing cells

Wed, 09/08/2017 - 16:14
Researchers have established a unique method enabling them to study the function of insulin-producing cells under conditions that are similar to those in humans. This can pave the way to development of new medicines for the treatment of diabetes. Beta cells in the pancreas produce the hormone insulin, which plays a key role in the regulation of blood glucose levels. In diabetes, there is a partial or complete loss of beta cell function. In order to understand how insulin-producing beta cells function, it is essential to be able to study them in a model that reflects the physiological and pathological processes in humans. The cornea as a window into the body In previous studies, Professor Per-Olof Berggren’s research group has shown that the structure and function of the hormone secreting part of the pancreas, the islets of Langerhans, are different in mice to those in humans, while those in monkeys are similar to those in humans. There is therefore a medical need to be able to study the islets of Langerhans in live monkeys. In a new study, recently published in the scientific journal Cell Reports, the researchers have developed a unique method for monitoring the function of insulin secreting beta cells from monkeys that have been transplanted into the anterior chamber of the eye of the same monkeys. This enables the cornea to be used as a window into the body, and to study beta cell function non invasively for a longer period of time.  “By using this human-like model, we have shown that blood vessels have an active and dynamic role with regard to the function of the islets of Langerhans in monkeys. This is an important study contributing to increased understanding of the physiology and pathology of human islets of Langerhans”, states Per-Olof Berggren, Professor at the Rolf Luft Research Centre for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery at Karolinska Institutet and Visiting Professor at Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, who has led the study. Idetify new regulatory steps Per-Olof Berggren points out that in the future, use of this technique will enable identification of not only new regulatory steps for the insulin secreting beta cells’ function and survival, but also of new medicines targeting these regulatory steps, which will be critical for treatment of diabetes. It may also be possible eventually to use this technique in the clinic to monitor the function of the hormone-secreting part of the pancreas.   The study has been conducted in collaboration between researchers at Karolinska Institutet, Lee Kong Chian School of Medicine, Nanyang Technological University and Singapore Eye Research Institute, Singapore General Hospital, Singapore. Publikation Pancreatic islet blood flow dynamics in primates Juan A. Diez, Rafael Arrojo e Drigo, Xiaofeng Zheng,Olga V. Stelmashenko,  Minni Chua, Rayner Rodriguez-Diaz, Masahiro Fukuda, Martin Köhler, Ingo Leibiger, Sai Bo Bo Tun, Yusuf Ali, George J. Augustine, Veluchamy A. Barathi, and Per-Olof Berggren, Cell Reports 20, 1–12, 8 August 2017, doi:10.1016/j.celrep.2015.08.05  

Hormone from fat tissue can give protection against PCOS

Wed, 09/08/2017 - 13:42
Obesity and reduced insulin sensitivity are common in polycystic ovary syndrome, PCOS. New research based on animal studies, and to be published in the journal PNAS, reveals that the hormone adiponectin can protect against these changes. Polycystic ovary syndrome, PCOS, affects more than one in ten women of fertile age. It is characterised by high levels of the male sex hormone testosterone and disrupted ovulation, which can cause infertility. PCOS is also often associated with overweight and an impaired ability to respond to the glucose-regulating hormone insulin, so-called insulin resistance. This in turn results in an increased risk of type 2 diabetes. An international research team, led by the University of Gothenburg and Karolinska Institutet, has previously shown that women with PCOS have lower levels of the fat tissue-derived hormone adiponectin. Furthermore, there is a strong link between low adiponectin levels, increased waistline, large fat cells and insulin resistance in these women. A causal relationship between the low adiponectin levels and the metabolic disturbances in PCOS has however not been proven. In this new study, the researchers therefore looked at two types of genetically modified female mice. In one group they studied mice with elevated levels of adiponectin, and in the other mice with a total lack of adiponectin. Half of the mice in each group received male sex hormone, which induces PCOS symptoms in normal mice. Mice with high levels of adiponectin were shown to be protected against PCOS-related metabolic disorders such as insulin resistance and abdominal obesity. However, adiponectin did not protect against disruption of ovulation. “The results show that adiponectin plays an important role in fat tissue function and probably also in the development of obesity and insulin resistance in women with PCOS. A drug that acts similarly as adiponectin may therefore be an effective future treatment of the metabolic disorders that affect women with PCOS”, says the researchers behind the study. The study has been financed in part by Vetenskapsrådet (Swedish Research Council), Novo Nordisk fonden, (Novo Nordisk Foundation), Diabetesfonden, Diabetes Wellness fonden (Diabetic Wellness Foundation), Adlerbertska fonden (Adlerbertska Foundation) and the Strategic Research Program (SRP) Diabetes Karolinska Institutet. Publication Adiponectin protects against development of metabolic disturbances in a PCOS mouse model. Anna Benrick, Belén Chanclón, Peter Micallef, Yanling Wu, Laila Hadi, John M. Shelton, Elisabet Stener-Victorin, Ingrid Wernstedt Asterholm. Proceedings of the National Academy of Sciences (PNAS), online 8 August 2017, doi: 10.1073/pnas.1708854114

Receptor dynamics provide new potential for pharmaceutical developments

Wed, 09/08/2017 - 13:14
The dynamics among certain so-called G protein-coupled receptors, of vital importance for the function of cells in the body, are different than previously believed.  This has been reported by researchers from Karolinska Institutet in the journal Nature Communications. As these types of receptors are the target for many different medicines, the new finding opens the doors to completely new opportunities within pharmacology and pharmaceutical development. G protein-coupled receptors belong to one of the largest protein families, with around 800 representatives in the human body that send numerous signals around the body. These receptors are found in the cell membrane and are activated by messenger molecules outside the cell, such as adrenaline, dopamine, histamine and endorphins. The receptors are not only important for cellular function by interpreting messages from outside the cell and subsequently activating signals inside the cell, they are also the target for a number of different and important medicines. Examples of such are betablockers, antihistamines, morphine and L-DOPA. Individually or in pairs The discovery of G protein-coupled receptors resulted in a Nobel Prize in Chemistry in 2012. It has been known for some time now that the receptors can act either individually or in pairs, as so-called dimers. Their capacity to function in different constellations has been seen as a challenge, but also an opportunity for pharmacology and pharmaceutical development. To date, the hypothesis has been that G protein-coupled receptors function either as individual receptors or in pairs, and that this is stable. An international team of researchers, led by a group from Karolinska Institutet, has now shown that a specific G protein-coupled receptor named Frizzled 6 (FZD6) can switch between acting in pairs and as an individual receptor, and that this switch is of vital importance for activation of the receptor. FZD6 is important for embryonic development and is significantly expressed in lung tissue. The new study demonstrates that the receptor acts in pairs when it is inactive, and that stimulation with messenger molecules results in the dimer separating into individual receptors, triggering the signals inside the cell. Pave the way for new medicines It remains to be seen whether the same dynamics can be found when activating other G protein-coupled receptors that can act in pairs. As such, the finding may pave the way for the development of new medicines that exploit the dynamics of these receptors. “It may be possible to develop pharmaceutical substances that have an inactivating effect by keeping active receptors in pairs, or vice versa, that activate the receptors by breaking down the dimers. Even if FZD6 cannot be considered a well-defined target for pharmaceutical development, the new concept of receptor dynamics is of utmost interest for many other G protein-coupled receptors and pharmaceutical treatment of many important diseases,” explains Gunnar Schulte, head of the group of researchers at the Department of Physiology and Pharmacology, Karolinska Institutet. He has carried out the study in cooperation with Julian Petersen and Shane Wright from the same Department, along with researchers from Uppsala University, SciLifeLab and the Hebrew University of Jerusalem, Israel. The research was made possible primarily via financing from Karolinska Institutet (KID), the Swedish Research Council, the Swedish Cancer Society, Science for Life Laboratory, the Swedish Foundation for Strategic Research, the Knut & Alice Wallenberg Foundation, Marie Curie ITN, Engkvists Stiftelser (charitable foundation), the Lars Hierta Memorial Foundation, Czech Science Foundation, COST Actions and Israel Science Foundation. Publication Agonist-induced dimer dissociation as a macromolecular step in G protein-coupled receptor signaling. Julian Petersen, Shane C. Wright, David Rodríguez, Pierre Matricon, Noa Laha, Aviv Vromen, Assaf Friedler, Johan Strömqvist, Stefan Wennmalm, Jens Carlsson & Gunnar Schulte, Nature Communications, online 9 August 2017.

Improved diagnostics for patients with traumatic brain injuries

Fri, 04/08/2017 - 09:02
A new study published in PLOS Medicine shows that by improving the classification of patients with traumatic brain injuries, a more accurate diagnosis and prognosis can be made. The results are the product of a collaboration between Karolinska Institutet, Karolinska University Hospital and Helsingfors University Hospital. Traumatic brain injury (TBI) is one of the most common causes of death and permanent disability in people worldwide. Traumatic brain injuries are caused by external forces directed towards the head such as falls, car accidents or physical abuse. This may result in bleeding inside the skull, in or around the brain. Previously, TBI was considered a disease of the young. Yet, today more and more elderly people are affected and treated for TBI because of the aging population and the increasing use of antithrombotic medications.   Patients who are suspected of having a bleed inside the skull are primarily diagnosed by computed tomography (CT) scanning of the brain. The CT scan provides a rapid diagnosis and shows if there are any bleedings that requires acute neurosurgical interventions. However, interpreting the results of CT scans is highly complex, particularly as different types of bleedings are often found. Various types of CT classification systems have been developed to standardise the interpretation of CT images in patients with traumatic brain injury (TBI). These take into consideration information from the CT scan and are used to determine the severity of the injury and to estimate patient outcome. “The problem with the earlier CT classification systems is that they are very crude and based on old patient materials. Improved and more updated CT classification systems have long been necessary”, says the study’s first author, Eric Thelin, doctor and researcher at the Department of Clinical Neuroscience, Karolinska Institutet. In order to get more information from CT scans, researchers and doctors at Karolinska Institutet and Karolinska University Hospital as well as Helsingfors University Hospital have developed a new way of classifying the brain injuries one can see using CT, the so-called “Stockholm CT score” or “Helsinki CT score”. A collaboration study has compared 1,115 patients who were treated for TBI in the Department of Neurosurgery Intensive Care Units in Stockholm and Helsinki. “The results show that by making a correct assessment of the first images obtained by CT, we can better predict how well the patients will fare. This is extremely useful as it gives the clinicians better information as to how their care can be optimised”, comments Eric Thelin. The study showed that classification using the Stockholm or Helsinki CT score can more reliably predict how well patients will progress in the next 6 to 12 months than previously used classification systems. It also found that the extent of diffuse brain injury a type of injury that without good treatment options, was the type of injury that most affected the patients’ prognosis. “Unfortunately, up to date there is little we can do to treat these diffuse brain injuries. But, aided by our results, we know that future research should be directed into the treatment of diffuse brain injuries. Finding effective treatment strategies for patients affected by this type of injury must be prioritised”, comments Rahul Raj, Adjunct Professor in Experimental Neurosurgery at Helsingfors University Hospital. The study has been financed by Svenska Läkaresällskapet [The Swedish Society of Medicine], Maire Taponens stiftelse [Maire Taponen’s Foundation], Maud Kuistilas minnesstiftels [Maud Kuistilas Memorial Foundation], Eemil Aaltonens stiftelse [Eemil Aaltonen’s Foundation], Ella och Georg Ehrnrooths stiftelse {Ella and Georg Ehrnrooth’s Foundation], Liv & Hälsa [Life and Health], den svenska kulturfonden i Finland [The Swedish Cultural Foundation in Finland], den finsk-norska medicinska stiftelsen [The Finnish-Norwegian Medical Foundation] and Finlands medicinska stiftelse [The Finnish Medical Foundation]. Publication Evaluation of novel computerized tomography scoring systems in human traumatic brain injury: An observational, multicenter study Thelin EP, Nelson DW, Vehviläinen J, Nyström H, Kivisaari R, Siironen J, Svensson M, Skrifvars MB, Bellander BM, Raj R PLOS Medicine, 3 August 2017, doi: 10.1371/journal.pmed.1002368.  

Heartburn medicine can increase risk of kidney disease

Wed, 02/08/2017 - 18:01
People who take proton pump inhibitors for stomach acid reflux run a greater risk of chronic kidney disease than those who take H2-receptor antagonists for the same complaint, a new study published in Gastroenterology reports. Proton pump inhibitors (PPIs) are amongst the most widely sold drugs in the world, including Sweden. Last year, almost ten per cent of the Swedish population took them to alleviate heartburn or prevent stomach ulcers. The first drug, Omeprazol, was launched at the end of the 1980s under the name Losec, but today there are numerous similar products on the market. These drugs spare many people the necessity of having to undergo ulcer surgery and as they are also very effective against heartburn they are extremely popular. Earlier research suggested that PPI’s may be associated with an increased risk of kidney disease. For this present study, researchers at Karolinska Institutet compared the risk of kidney damage on taking PPIs with the somewhat less potent H2-receptor antagonists. The observation study was conducted on some 100,000 long-term users of PPIs from Stockholm and just under 10,000 equally long-term users of H2-receptor antagonists. They found that PPI users had a 26 per cent higher risk of developing chronic kidney disease compared to those who used H2-receptor antagonists and that there was also a correlation between PPI and acute kidney disease. The risk of kidney damage also increased with higher dose taken. The team stresses that the study only indicates a correlation and does not imply causation. However, since millions of people take these drugs every day, a relatively rare adverse reaction can affect a large number of people. “Doctors need to weigh up the pros and cons much more when prescribing PPIs, and revise periodically the need to continue or not with the treatment” says lead author Juan Jesus Carrero, docent at Karolinska Institutet’s Department of Medical Epidemiology and Biostatistics. “Many people take PPIs for years and without a clear indication. These drugs should not be taken if they’re not needed, the dose should be cut to the minimum necessary. The possibility to use a H2-receptor antagonist instead should be also contemplated. There might also be reason for patients on long-term PPI medication to take annual kidney function tests. We hope that our results will make the public and the prescribing doctors more aware of the risks of this adverse reaction.” The study was carried out in collaboration with Stockholm County Council, Leiden University (Netherlands) and Johns Hopkins University (USA), and financed by grants from several bodies, including the Swedish Heart and Lung Foundation. None of the researchers have reported any commercial interest in the study. Publication Association Between Proton Pump Inhibitor Use and Risk o Progression of Chronic Kidney Disease. Derk C.F. Klatte, Alessandro Gasparini, Hong Xu, Pietro de Deco, Marco Trevisan, Anna L.V. Johansson, Björn Wettermark, Johan Ärnlöv, Cynthia J. Janmaat, Bengt Lindholm, Friedo W. Dekker, Josef Coresh, Morgan E. Grams, Juan J. Carrero. Gastroenterology, online 2 August 2017, DOI:

Mutations occurring after fertilisation could play a role in autism

Wed, 26/07/2017 - 15:33
A new study published in the journal Nature Neuroscience, looking at some 6,000 families, demonstrates that mutations that occur after fertilisation play an important role in autism.  Over the last decade, mutations in more than 60 different genes have been linked to autism spectrum disorders (ASD). Some of these are spontaneous, non-inherited mutations and are present in only a few of our cells. Such mutations can occur in a sperm or egg, or in some of the embryo’s cells after fertilisation. These mutations are called postzygotic mutations, PZMs, or somatic mutations. The later the PZMs occur during embryonal development, the fewer the cells that will carry them, making it more difficult to detect them. If the mutation occurs in a very small percentage of the cells, there is a risk it will be missed during regular gene mapping, so-called exome sequencing. To detect PZMs, researchers in the new study used data that had previously been collected from 5,947 families who had a child with autism spectrum disorder. They then re-sequenced parts of the DNA from these children using three independent sequencing techniques in parallel. This mapping revealed that 7.5% of the children had autism spectrum disorder that was related to PZMs. Of these, 83% had not been detected at the original analysis of their genome. Some PZMs affect genes that are known to be linked with autism or other neuropsychiatric disorders, while others affect genes that are known to be active in brain development but have not previously been linked with ASD. By comparing sequencing data, which is primarily on DNA from blood, with data from the public brain banks, which shows when in development (from fetus to adult) these genes are expressed, the researchers also discovered the time point in development when the mutations occurred, and in which areas of the brain they occurred. These analyses showed that PZMs in individuals with ASD occur disproportionately often in the amygdala. “This was exciting for us because the amygdala has been proposed as a region of the brain that is important in autism. The study contributes by further supporting the hypothesis that complex disturbances in the brain, such as epilepsy, intellectual disorders, schizophrenia and brain malformations, can originate from non-inherited mutations that occur at a certain point in prenatal development”, says Christina Hultman, Professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet and responsible for Swedish data on autism. Publication Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder Elaine T Lim et al, Nature Neuroscience, online 17 July 2017, doi: 10.1038/nn.4598

New strategy against childhood cancer

Wed, 26/07/2017 - 15:16
Neuroblastoma is a cancer in children that originates in the sympathetic nervous system and has a high mortality. Current treatment includes chemotherapy and radiotherapy with their potentially severe side effects; there is therefore an urgent need for a new improved drug.  One potential treatment strategy is to use a drug to target deviant molecular signalling caused by changes in genes. The Wingless (Wnt) signalling pathway is important in the development of nerve cells. One current study has shown that approximately one in four neuroblastoma patients have at least one gene change in the part of the Wnt signalling pathway that is important for cell maturation and migration, the so-called Rho/Rac signalling pathway. “Our results indicate that the signalling molecule Rho and the enzyme Rho kinase, ROCK, have been activated in neuroblastoma patients. High expression of the ROCK enzyme has been shown to be linked to poorer survival of the patients”, comments Cecilia Dyberg, researcher at the Department of Women's and Children's Health, Karolinska Institutet and first author of the study which will be published in the journal PNAS. In studies on cells in vitro and in mice, the researchers observed that when they inhibited ROCK, the tumour cells differentiated, i.e. they matured to less harmful cells, and the tumours stopped growing. The researchers also saw that inhibiting the ROCK enzyme caused the MYCN oncogene, which is linked to the incidence of neuroblastoma, to be degraded to a greater extent and disappear. In some parts of the world, the drug used to target ROCK is used clinically to treat diseases other than cancer, and researchers believe that similar drugs targeting Rho/Rac signalling can be a new promising treatment for neuroblastoma. This research has been financed by grants from the Swedish Childhood Cancer Foundation, the Swedish Research Council, Swedish Cancer Society, the Swedish Foundation for Strategic Research, Märta and Gunnar V. Philipson’s Foundation, Mary Béve’s Foundation for Childhood Cancer Research, Eva and Oscars Ahrén’s Foundation, Magnus Bergvall’s Foundation, Anna-Brita and Bo Castegren’s Memorial Foundation and the Cancer Research Funds of Radiumhemmet. Publications Rho-associated kinase is a therapeutic target in neuroblastoma Cecilia Dyberg, Susanne Fransson, Teodora Andonova, Baldur Sveinbjörnsson, Jessika Lännerholm-Palm, Thale K. Olsen, David Forsberg, Eric Herlenius, Tommy Martinsson, Bertha Brodin, Per Kogner, John Inge Johnsen and Malin Wickström. PNAS, Proceedings of the National Academy of Sciences, online 24 July 2017, doi: 10.1073/pnas.1706011114

Higher calcium levels and risk of coronary artery disease

Wed, 26/07/2017 - 10:22
A genetic predisposition to higher blood calcium levels was associated with an increased risk of coronary artery disease and heart attack, according to a study published by JAMA. Calcium has a vital role in many biological processes in the body such as blood clotting. It is unclear whether lifelong elevated serum calcium may be causally associated with coronary artery disease (CAD) risk. Susanna C. Larsson, PhD, of the Karolinska Institutet, Stockholm, and colleagues conducted a method of analysis using genetic information known as mendelian randomization to examine the association of serum calcium with CAD and myocardial infarction (MI; heart attack). Mendelian randomization is the use of genetic variants that have a specific influence on possible risk factors to assess associations with explicit outcomes. The analysis included 184,305 individuals (60,801 CAD cases [approximately 70 percent with MI] and 123,504 noncases) and six genetic variants related to serum calcium levels. The researchers found that a genetic predisposition to higher serum calcium levels was associated with an increased risk of CAD and heart attack. “Whether the risk of CAD associated with lifelong genetic exposure to increased serum calcium levels can be translated to a risk associated with short-term to medium-term calcium supplementation is unknown,” the authors write. Publication Association of Genetic Variants Related to Serum Calcium Levels with Coronary Artery Disease and Miocardial Infarction Susanna C. Larsson, Stephen Burgess, Karl Michaëlsson JAMA, 25 juli 2017, 2017;318(4):371-380, doi:10.1001/jama.2017.8981

Reduction in dental care and inferior oral health subsequent to dementia diagnosis

Wed, 26/07/2017 - 08:00
Subsequent to a diagnosis of dementia, the patient’s contact with the dental care services diminishes and oral health is impaired. This has been revealed by a major register-based study from Karolinska Institutet published in the scientific journal Alzheimer’s & Dementia. Researchers at Karolinska Institutet, using register data, have examined utilisation of dental health services and oral health among a large number of individuals before and after a dementia diagnosis. Information on diagnoses and cognitive function has been compiled for around 58,000 persons registered in the Swedish Dementia Registry, SveDem, from 2007 to 2015. Information relating to dental health was obtained from Tandhälsoregistret (dental health registry). “We observed that the number of visits to dentists saw a dramatic decrease after a dementia diagnosis and that the reduction in utilisation of dental health services was more predominant with patients who experienced a more rapid degeneration in cognitive function,” explains Maria Eriksdotter, Professor of Geriatrics at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. A low MMSE score (Mini-Mental State Examination) – a method used to indicate cognitive impairment – represented a risk factor in terms of losing teeth. Poor oral health, tooth decay and loosening of teeth may cause pain, reduced quality of life and difficulties eating, resulting in poor nutrition. “It may be the case that patients forget to visit the dentist or put other types of health care first, as dental care is separate from other medical services. We require better organisation to detect these patients and ensure that they attend their dental health check-ups,” says Gunilla Sandborgh Englund, Professor at the Department of Dental Medicine, Karolinska Institutet. The research has been financed by Alzheimerfonden (the Swedish Alzheimer foundation), Stockholm County Council (the SOF project), the Swedish Research Council and the Swedish Association of Local Authorities and Regions. Publication Dental care utilization in patients with different types of dementia. A longitudinal nationwide study of 58037 individuals, Seyed-Mohammad Fereshtehnejad, Sara Garcia-Ptacek, Dorota Religa, Jacob Holmer, Kåre Buhlin, Maria Eriksdotter, Gunilla Sandborgh-Englund, Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, online 8 July 2017, doi: 10.1016/j.jalz.2017.05.004

Professor Allen Counter is dead

Thu, 20/07/2017 - 13:47
The brain researcher and neurophysiologist Professor Allen Counter has passe away after a time of illness. Counter was a professor at Harvard University and foreign adjunct professor at Karolinska Institutet, KI. He had strong ties to Sweden, and in 2004 he was appointed General Council of Sweden to Boston and New England. “Allen was a true friend of KI and Sweden, and through his extensive international network or in research, health care, politics, industry and the arts, he contributed in a unique way to strengthen KI in the international arena. Allen will be deeply missed”, says Jan Hillert, Head of the Department of Clinical Neuroscience, where Counter was a foreign adjunct professor. ´ Counter was a clinical professor of neurology at Harvard University and worked as a neurophysiologist at the Massachusetts General Hospital in Boston, USA. He also played d a key role as the Head of the Harvard Foundation for Intercultural and Race Relations. Counter was very successful in attracting research funding from the private sector. Counter had longstanding and strong ties to KI and Sweden. He joined KI as a visiting researcher in 1978 and remained connected to KI until his death. He earned his Ph D at KI’s Department of Physiology in 1992, and was appointed visiting professor in 2009. In 2015 he was appointed foreign adjunct professor. Counter collaborated with many scientists at KI, especially Professor Erik Borg, Professor Tom Brismar, Professor Lou Brundin and Professor Tomas Olsson. "Allen remained extremely loyal to KI and he was equally as loyal as a colleague and friend", says Professor Tomas Olsson. Counter also collaborated with researchers at other universities in Sweden, especially Professor Göran Laurell at the Department of Surgical Sciences at Uppsala University. Counter’s research evolved around the inner ear and brain development. Allen Counter was 73 years old.

KI's research impact top rated in research barometer

Tue, 18/07/2017 - 15:12
KI’s research is at the leading edge of impact according to the Swedish Research Council’s (SRC) Research Barometer for 2017 with the highest proportion of highly cited publications compared to other universities and colleges in Sweden. The SRC’s Research Barometer provides an overview of the state of Swedish research through some thirty indicators including financial resources, research staff and results generated by way of research publications and citation impact. This year’s barometer shows KI to have had the highest citation impact for scientific articles published during the period of 2013-2015 with the number of highly cited publications rising from 12 percent in 2008-2010 to 14 percent in 2013-2015.

Fewer infections in mechanical heart valves

Tue, 18/07/2017 - 10:21
Infections in surgically implanted heart valves are more common in patients who have been given a biological prosthetic valve than in those with a mechanical one, a study from Karolinska Institutet published today in the journal Circulation shows. Some 1,500 people undergo aortic valve replacement every year in Sweden, about 75 per cent of whom receive a biological valve (from a pig or calf), the remainder a mechanical one. A complication that carries a high fatality risk is prosthetic valve endocarditis, which occurs when the new valve is infected by bacteria. Until now, there have been no figures on whether the infection frequency differs between the two valve types. It has also been unknown how common infections in an artificial heart valve are. The present study included over 26,500 patients who received a prosthetic heart valve between 1995 and 2012, 940 of whom developed prosthetic valve endocarditis. The risk of infection in the artificial valve was about 50 per cent higher with a biological prosthesis than with a mechanical. The follow-up time was up to 18 years. “We hadn’t expected this large difference,” says Natalie Glaser, doctoral student at Karolinska Institutet’s Department of Molecular Medicine and Surgery. “Our results are important as they tell us more about complications following the surgical replacement of aortic valves.” The current European cardiology guidelines state that there is no difference in the incidence of infection between the two types of implant. Dr Glaser argues that this could be because former studies were too small to reveal any difference and were done on patients who were operated on decades ago.  The present study has also provided updated figures on the commonality of the complication, which affected a total of around 0.5 per cent of patients per year. It also shows that the fatality rate was as high as 16 per cent within a month of diagnosed infection and 50 per cent within five years. “The choice of valve prosthesis is very much decided by the patient’s age,” says principal investigator Ulrik Sartipy, heart surgeon at Karolinska University Hospital and docent at Karolinska Institutet’s Department of Molecular Medicine and Surgery. “Biological valves are usually used for older patients for medical reasons, partly because such valves do not require life-long treatment with anticoagulants. In our study, those who had received biological valves were on average 13 years older than those who were given mechanical ones, but this we’ve compensated for in our comparison.” The study was financed with grants from several bodies, including the Swedish Heart and Lung Foundation, the Mats Kleberg Foundation and the Magnus Bergvall Foundation. Martin Holzmann has reported that he receives a consultancy fee from Actelion and Pfizer. Publication Prosthetic valve endocarditis after surgical aortic valve replacement Natalie Glaser, Veronica Jackson, Martin Holzmann, Anders Franco-Cereceda and Ulrik Sartipy Circulation, online 17 July 2017,

Multimillion grant to KI researcher from AFA Försäkring

Mon, 17/07/2017 - 11:27
Jenny Selander, researcher at the Institute of Environmental Medicine (IMM), is to receive SEK 8 million from AFA Försäkring for research on how physical and chemical work environment risks affect the risk of developing cardiac and vascular diseases. Earlier studies indicate that exposure to physical and chemical work environment factors can elevate the risk of cardiac and vascular disease. Few studies, however, have focused on the impact when people are exposed to more than one environmental risk of heart and vascular disease in women in particular, or taken health and socioeconomic status in early life into consideration.  The project “Cardiac diseases in people of working age – a unified approach to determine the significance of the physical and chemical work environment” studies concurrent effects, gender-specific differences in risk and individual risk factors. Examples of the kind of work environment risk focused on include noise, air pollution, vibrations, and physical and strenuous work. The project is expected to contribute to explaining the relationship between physical and chemical work environment factors and the risk of cardiac and vascular disease. It is hoped that it will also lead to possibilities to design better preventive work. AFA Försäkring is making grants totalling SEK 50 million to six new research projects within the framework of an R&D programme focusing on research for a working life without cardiac and vascular diseases.

Research is the key to a better mental health among young people

Thu, 13/07/2017 - 14:36
Universities have an important role to play in combating the increase in mental ill-health among children and adolescents. More resources should be devoted to research in this field. These are the views of many of the participants at the seminar that KI organised in Almedalen. “The incidence of self-reported mental ill-health among boys and girls has doubled over the past 30 years. In addition, the suicide rate is not decreasing among young people as it is in all the other age groups”, said Magnus Jägerskog, Secretary General of Bris, Children’s Rights in Society. He presented a new report on mental ill-health among children, produced in collaboration with Sven Bremberg, researcher at the Department of Public Health, Karolinska Institutet. However, the cause of this increase in mental ill-health among children is unclear, with more research needed in order to find answers. Magnus Jägerskog argued that society has fallen short, and continues to fall short, when it comes to supporting children and adolescents. “According to the UN Convention on the Rights of the Child, which has now also become law, children have a right to have their voices heard in matters which concern them. But when children describe their perceptions of healthcare, we see a number of problems”, he said. He highlighted several proposed measures that he believed would require broad political reforms. Examples included equal care for children throughout the country, investments in jobs for young people and investments in training in child and adolescent psychiatry. Bris also collected a petition containing 10,000 names under the heading of #psykbryt, demanding: Equal care in all county councils. More funding for research into mental ill-health. That every case of child suicide be investigated. What can we do to improve children’s mental health? Danuta Wasserman is a professor in the Department of Public Health, KI, and has extensive experience of working with suicide prevention. She presented a method which her research group had evaluated in partnership with researchers from a range of other European countries. “Our research indicates that by helping people to help themselves, you can reduce the rate of attempted suicide by 50 per cent and the incidence of depression by 30 per cent among young people”, she said.  Pupils are able to take part in interventions such as a supervised role play in which they can explore their feelings and learn coping strategies. She quoted one participant: “This is the first time in my life that my friend has said he has also been suffering from poor mental health and I have now realised that other people can feel as bad as I have”. “This is the first time in my life that my friend has said he has also been suffering from poor mental health. The method is now being introduced in Stockholm County in order to improve mental health and reduce the number of suicides and attempted suicides among school pupils. Danuta Wasserman also took the opportunity to provide some general advice on how to improve your mental health: sleep, exercise, read books and watch films.  “This is really nothing new, this is something even my grandmother knew. But it bears repeating. Schools and society as a whole need to embrace these simple suggestions”, she said. Another KI researcher who is focusing on mental ill-health is Emily Holmes, a professor in the Department of Clinical Neuroscience. She spoke about her research into post-traumatic stress disorder (PTSD), a condition that can emerge following severe traumatic experiences, for example war. People with PTSD often experience intrusive memories, known as flashbacks, in which they involuntarily relive moments from these experiences. “We have found that the computer game Tetris, combined with other behavioural psychology interventions, can reduce the incidence of flashbacks”, she said. A small study has been carried out among young refugees who have recently arrived in Sweden. Emily Holmes presented figures that indicated mental ill-health accounts for more than 15 per cent of the total burden of disease in the West, which is greater than all forms of cancer combined. However, barely two per cent of the research budget is spent on mental ill-health in the EU.  “We need research in order to evaluate the methods we use today, but also to find new treatment methods. Children and adolescents have their whole lives ahead of them; we have the chance to make a difference!  Children and adolescents have their whole lives ahead of them; we have the chance to make a difference!  The subsequent debate also featured Ida Höckerstrand and Sofie Hallberg, the instigators of Ångestpodden [the Anxiety Podcast], Mikael Dahlqvist, Social Democrat politician and member of the Riksdag’s Committee on Health and Welfare, and KI’s Acting Vice-Chancellor Karin Dahlman-Wright. The moderator Carl Johan Sundberg asked: How can we reach out to young people? “We started Ångestpodden because we felt that it was needed. We think that our podcast has become popular because we speak the same language as young people. It is important to talk with young people, rather than about them. We give them a voice”, said Sofie Hallberg. Ångestpodden has over 30,000 listeners each month. “Many of the young people who contact us are suffering, but don’t have anyone to talk to. They don’t know where to turn. That’s not how it should be”, said Ida Höckerstrand. She argued that it would be interesting to see research that investigated the link between mental ill-health and the fact that many young people are currently living a large part of their lives on social media. Who is responsible for the issue of mental ill-health? “The Swedish Government is responsible for ensuring that Sweden complies with the Convention on the Rights of the Child”, said Magnus Jägerskog. Mikael Dahlqvist confirmed that this is an important issue. “This is a serious situation we are faced with. Swedish municipalities and county councils have initiated a number of projects in this area”, he said. Karin Dahlman-Wright, Acting Vice-Chancellor of KI, pointed out that health services have responsibility for providing healthcare, but that universities have a responsibility to disseminate existing knowledge and ensure that society benefits from research.  “We also have to test and evaluate methods – and turn back if need be. Researchers also need to determine what problems need solving. What can be more important than ensuring that our children and adolescents are well”, she said. Text and photo: Cecilia Odlind

New potential treatment for aggressive types of childhood cancer

Tue, 11/07/2017 - 08:01
A combination of substances that impacts chemical modifications in the DNA of tumours and triggers the tumours to differentiate into harmless nerve cells could represent a new method of treating aggressive forms of neuroblastoma. The new method has been proposed by researchers at Karolinska Institutet, after studies using mice showed that the combination treatment resulted in a significant suppression in tumour growth. The study, published in PNAS, also questions a hypothesis within the research field that could result in potentially harmful wrong treatment of children with neuroblastoma. Neuroblastoma affects the peripheral nervous system in children and is a tumour disease with different facets. A number of these tumours disappear naturally and others respond well to the treatment available. There are however some types of neuroblastoma that are very aggressive and, in many cases, do not respond to treatment. Mortality among these high-risk patients is high and there is therefore a substantial requirement for new and efficient methods of treatment. Significant suppression in tumour growth During the study, the researchers treated mice with the substance AZA, which blocks and eliminates methyl groups from the DNA of cancer cells, aiming to activate genes that fight the origins of neuroblastoma. AZA was then combined with treatment with retinoic acid (RA), a substance that has the capacity to make certain tumour cells differentiate, mature, into harmless nerve cells. Neither AZA nor RA could individually suppress the growth of high-risk tumours, but the combination treatment resulted in a significant suppression in tumour growth in the mice. The treatment induced expression of a factor called HIF2α, why the researchers also tested a combination with a HIF2α inhibitor. Such inhibitors have been proposed as an alternative treatment for neuroblastoma as the HIF2α protein has previously been described as being coupled to more aggressive forms of neuroblastoma. HIF2α inhibitor are currently being subject to clinical trials for treatment of other tumour diseases. “Interestingly, it emerged that the effect of our combination treatment with AZA and RA was, in fact, counteracted by the HIF2α inhibitor. Moreover, analyses of large volumes of patient data show that HIF2α is not coupled to aggressive types of neuroblastoma, but can be linked to a lower risk and improved survival for patients,” explains Johan Holmberg, researcher at the Ludwig Institute for Cancer Research and the Department of Cell and Molecular Biology at Karolinska Institutet. Potentially harmful wrong treatment with HIF2α The role played by the HIF2α inhibitors requires further study before they can be used to treat neuroblastoma patients,” confirm the researchers. “In addition to demonstrating the effect of a new potential combination treatment, our study questions a hypothesis that may result in potentially harmful wrong treatment of children with neuroblastoma. The study could therefore be of importance for future clinical applications,” says Johan Holmberg. The research has been financed by StratCan, the Swedish Cancer Society, the Swedish Childhood Cancer Foundation, the Swedish Research Council, the Ludwig Institute for Cancer Research and the Knut and Alice Wallenberg Foundation. Publication: “Combined epigenetic and differentiation based treatment inhibits neuroblastoma tumor growth and links HIF2α to tumor suppression”. Isabelle Westerlund, Yao Shi, Konstantinos Toskas, Stuart M Fell, Shuijie Li, Olga Surova, Erik Södersten, Per Kogner, Ulrika Nyman, Susanne Schlisio & Johan Holmberg. Proceedings of the National Academy of Sciences (PNAS), online 10 July 2017. For more information, please contact: Johan Holmberg, researcher The Department of Cell and Molecular Biology, Karolinska Institutet The Ludwig Institute of Cancer Research Tel: +46 (0)72-221 27 02 Email:

New tool demonstrates differences in human immune systems

Tue, 11/07/2017 - 08:00
Immune system function varies significantly between individuals, and up to now there has been no effective means of measuring and describing these differences. Now, researchers at Karolinska Institutet have shown that white blood cell composition is unique in individuals, and that the composition of these cells may predict immune system response to various forms of stimulation. The study, which is published in PNAS, paves the way for more individualised treatment of diseases involving the immune system, e.g. autoimmune disorders, allergies and various forms of cancer. The human immune system comprises a complex network of different white blood cells, which coordinate their efforts in order to combat different external and internal threats. This network varies widely between different individuals, but the differences have been difficult to measure and understand. Together with colleagues at the Massachusetts Institute of Technology (MIT) and Stanford University in the USA, researchers at Karolinska Institutet and the Science for Life Laboratory (SciLifeLab) have developed a tool for measuring the unique composition of white blood cells in individuals. Researchers have also found that the test may predict how individuals will respond to a given treatment, e.g. individual response to an influenza vaccine. Measuring the individual’s “immunotypes” “By measuring all populations of white blood cells in the blood at the same time, we can describe the composition of an individual’s immune system and show that this is unique for the individual. We call this measure, the individual’s “immunotype”. We have also found that this immunotype makes the complex immune system more understandable and predictable,” says Petter Brodin, physician and researcher at SciLifeLab and the Department of Medicine, Solna, at Karolinska Institutet. A human immunotype is not constant, but varies over time in response to external factors. In previous studies, Petter Brodin and his research colleagues have shown that in humans individual differences in immune defence can be attributed primarily to the many different environmental factors unique to each individual, e.g. diet, infections, vaccines and microflora. Blood samples from 1,500 individuals In the study in question, the researchers analysed blood samples from approximately 1,500 healthy individuals and tested in vitro how their white blood cells respond to different stimuli. They have also vaccinated individuals against influenza and studied which antibody protection the individuals developed thereafter. It transpired that all different types of stimulation could be predicted based on the individual’s immunotype, which was surprising – according to Petter Brodin. "Our technique can be scaled up, and my hope is that eventually it will be used clinically to predict those individuals who may benefit from a particular immunological treatment or a certain vaccine. The technique may also contribute to more individualised drugs to treat autoimmune disease and allergies, as well as immunotherapy to treat cancer, which can be adapted based on the individual’s immune response,” says Petter Brodin. The study was financed by the National Institute for Health (NIH), the Ragon Institute of MGH, MIT and Harvard, the National Science Foundation, the European Research Council (ERC starting grant), the Swedish Research Council, the Swedish Society for Medical Research, the Swedish Cancer Society and Karolinska Institutet. Publication: "Continuous Immunotypes describe human immune variation and predict various responses".  Kevin J. Kaczorowski, Karthik Shekhar, Dieudonné Nkulikiyimfura, Cornelia L. Dekker, Holden Maecker, Mark M. Davis, Arup K. Chakraborty, Petter Brodin. Proceedings of the National Academy of Sciences (PNAS), online 10 July 2017. For more information, please contact: Petter Brodin, physician, researcher Department of Medicine, Solna, Karolinska Institutet Science for Life Laboratory (SciLifeLab) Phone: +46 (0)8 524 813 96 Email: