Integrative Molecular Phenotyping
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DEPARTMENT OF MEDICAL
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WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

KI News

Updated: 1 hour 19 min ago

New cell model could lead to treatments for neurological diseases

Fri, 16/02/2018 - 09:02
Researchers from Karolinska Institutet and KTH Royal Institute of Technology have developed a new cell model for human brain helper cells known as astrocytes. The model could potentially be used in large-scale drug screening in the search for treatments for neurological diseases such as Alzheimer’s. The research is published in the scientific journal Stem Cell Reports. Astrocytes are star shaped cells that are found in the brain and spine and were long thought to be the “glue” that binds nerve cells. However, recent advances show that they are in fact responsible for complex regulation of a variety of critical brain functions. They have also proven to be central to neurological diseases such as Alzheimer’s. But for research, these cells prove problematic. “Human astrocytes are significantly more complex than those found in mice, for example, mice do not develop the same brain diseases as humans. We therefore need better ways to study this cell type”, says Anna Falk, associate professor at Karolinska Institutet’s Department of Neuroscience. Nobel Prize-winning technology Together with Anna Herland at KTH and researchers at AstraZeneca, Anna Falk developed a new cell model for human astrocytes. Drawing on Nobel Prize-winning technology, the researchers reprogrammed human skin cells to create induced pluripotent stem cells, or iPS cells, which were then guided with growth factors to become astrocytes. Beginning with stem cells, researchers can produce an infinite number of astrocytes, which is important for the large-scale use within the pharmaceutical industry. “The historically high statistics of clinical failures in developing drugs against neurological diseases have now made drug companies increasingly interested in improved cell models in which human cells are used,” says Anna Herland, assistant senior lecturer at the Department of Micro and Nanosystems at KTH. “Our work has been focused on development of a cell model that follows human embryonic development of astrocytes.” Shows wider functionality Compared with cell models used in the pharmaceutical industry today, Falk and Herland’s model shows wider functionality. A pilot drug screening with a few substances showed that the model has the potential to identify new candidates which can go into drug development for neurological diseases. "Our model of human astrocytes is an important step forward in order to understand and attack human neurological diseases where astrocytes have an important role,” says Anna Herland. “With this model, we can begin to study how astrocytes develop and receive their functional diversity during embryonic development”. The research was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, Vinnova, the European Commission, the Wallenberg Foundations, and the Swedish Knowledge Foundation. This news article is based on a press release from KTH. Publication ”Human iPS-derived astroglia from a stable neural precursor state show improved functionality compared to conventional astrocytic models” Lundin Anders, Delsing Louise, Clausen Maryam, Ricchiuto Piero, Sanchez José, Sabirsh Alan, Mei Ding, Synnergren Jane, Zetterberg Henrik, Brolén Gabriella, Hicks Ryan, Herland Anna, Falk Anna Stem Cell Reports, online 15 February 2018, doi: 10.1016/j.stemcr.2018.01.021

Successful NK cell-based immunotherapy for leukaemia

Thu, 15/02/2018 - 11:48
Researchers at Karolinska Institutet have explored NK cell-based immunotherapy on patients with treatment-resistant leukaemia. The study, which is published in the scientific journal Clinical Cancer Research, shows that the new therapy is effective against several types of leukaemia. NK (natural killer) cells are a special type of white blood cell discovered at Karolinska Institutet in the 1970s that can recognise and kill cancer cells. In recent years, much knowledge has been generated on the biology of the cells and their ability to recognise tumour cells. Research into immunotherapy, in which the immune system is stimulated to attack cancer cells, has also made great strides forward. The potential of NK cells as a form of immunotherapy has not, however, been fully explored. Researchers at Karolinska Institutet have now tested an NK cell-based immunotherapy on 16 patients with treatment-resistant leukaemia of the types myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) or transitional MDS/AML phases. The patients were treated with activated NK cells from related donors. Some patients became symptom-free Six of the patients displayed objective responses to the treatment, some even attaining complete remission and thus becoming symptom-free. Five of these six patients became healthy enough to undergo curative stem cell transplantation, an intervention that was not possible before the NK cell treatment. Three of them have now survived for over three years, one for over five. The infusion of NK cells produced no serious adverse effects. “Our study shows that patients with MDS, AML and MDS/AML can be treated with NK cell-based immunotherapy and that the therapy can be highly efficacious,” says Professor Hans-Gustaf Ljunggren at Karolinska Institutet’s Department of Medicine in Huddinge, who initiated and led the study with departmental colleague Professor Karl-Johan Malmberg. Open the way for new clinical studies “The results open the way for new clinical studies, where there is potential for further improvements to study design that includes producing the next generation of NK cell-based immunotherapy,” says Andreas Björklund, specialist doctor at Karolinska University Hospital, who had clinical responsibility for the patients treated using the new therapy. The study was financed by several bodies, including the Tobias Foundation, the Swedish Cancer Society, the Swedish Research Council and Stockholm County Council. Jeffrey S. Miller and Karl-Johan Malmberg serves on the Scientific Advisory Board of Fate Therapeutics. Hans-Gustaf Ljunggren serves on the Scientific Advisory Board of CellProtect Nordic Pharmaceuticals and HOPE Bio-Sciences; on the Board of Directors of Vycellix; and is a collaborator with Fate Therapeutics. Publication “Complete Remission with Reduction of High-risk Clones following Haploidentical NK Cell Therapy against MDS and AML” Andreas T. Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L. Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S. Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina Wikström, Pontus Blomberg, Björn Engelbrekt Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg Clinical Cancer Research, online 14 February 2018, doi: 10.1158/1078-0432.CCR-17-3196

Possible new principle for cancer therapy

Thu, 15/02/2018 - 09:09
A study published in Science Translational Medicine shows that small molecules that specifically inhibit an important selenium-containing enzyme may be useful in combating cancer. When researchers at Karolinska Institutet treated cancer in mice using these molecules, they observed rapid tumoricidal effects. Researchers now hope that this new principle for cancer treatment will eventually be developed for use in humans. Humans need the chemical element selenium for good health. The selenium-containing enzyme thioredoxin reductase 1 (TrxR1) can be used to support the growth of various cells and to protect them from harmful forms of oxygen radicals, known as oxidative stress. Selenium intake has long been a topic of discussion in connection with cancer, although results have proved inconclusive and the correlation between selenium intake and cancer growth is extremely complex. Raised levels of TrxR1 can be seen in several forms of cancer and are linked to worse prognoses in head and neck, lung and breast cancers. Researchers therefore analysed almost 400,000 different molecules in the search for new and more specific TrxR1 inhibitors than those previously available. They discovered three different molecules that met their search criteria. Sure enough, when tested, these same molecules also proved to be active as cancer medicines. It proved possible to effectively treat over 60 different types of cancer cell under laboratory conditions. Normal cells were however much less sensitive to these molecules. Sensitive to oxidative stress “This effectiveness against cancer may be a result of cancer cells’ seemingly greater sensitivity to oxidative stress when compared to normal cells, which in turn can be utilised in cancer therapy,” says Professor Elias Arnér, Department of Medical Biochemistry and Biophysics at Karolinska Institutet, who led the study. Researchers also found rapid tumoricidal effects when treating head and neck or breast cancers in mice, without obvious side-effects. The new molecules have yet to be tested on humans, but it is already known that several different cancer medicines currently in use, including cisplatin and melfalan, inhibit TrxR1. Thus far, whether or not this inhibition of the enzyme is important to the effectiveness of these medicines has remained unknown, but this study suggests that this might well be the case. Researchers now intend to further develop the new TrxR1 inhibitors to offer a new form of cancer therapy. Effective against multiple forms of cancer “My hope is that we will be able to develop new treatments, effective against multiple forms of cancer but with few side-effects. This seems to work in mouse models and we are therefore hopeful that this principle for treatment can be developed for humans, even if this will require many years of further research,” says Elias Arnér. The study has been carried out in collaboration with researchers at the National Institutes of Health (NIH) in the United States. This research was funded by Karolinska Institutet, the Swedish Research Council, the Swedish Cancer Society, the Swedish Foundation for Strategic Research, the Knut and Alice Wallenberg Foundation, NIH, National Center for Advancing Translational Sciences, the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research and Oblique Therapeutics AB. Elias Arnér and NIH are listed as applicants for three patents based on the discoveries made in this study, with several co-authors named as co-inventors. Owe Orwar and William C Stafford are employees and shareholders in a company that develops TrxR1 inhibitors for clinical use. Publication ”Irreversible inhibition of cytosolic thioredoxin reductase 1 as a mechanistic basis for anticancer therapy” William C Stafford, Xiaoxiao Peng, Maria Hägg Olofsson, Xiaonan Zhang, Diane K Luci, Li Lu, Qing Cheng, Lionel Trésaugues, Thomas S Dexheimer, Nathan P Coussens, Martin Augsten, Hanna-Stina Martinsson Ahlzén, Owe Orwar, Arne Östman, Sharon Stone-Elander, David J Maloney, Ajit Jadhav, Anton Simeonov, Stig Linder och Elias S.J. Arnér Science Translational Medicine, online 14 February 2018, doi: 10.1126/scitranslmed.aaf7444

Atlas of brain blood vessels provides fresh clues to brain diseases

Wed, 14/02/2018 - 19:00
Even though diseases of the brain vasculature are some of the most common causes of death in the West, knowledge of these blood vessels is limited. Now researchers from Uppsala University and Karolinska Institutet present in the journal Nature a detailed molecular atlas of the cells that form the brain’s blood vessels and the life-essential blood-brain barrier. The atlas provides new knowledge regarding the functions of the cells and the barrier, and clues to which cell types are involved in different diseases. The vasculature of the brain is, like elsewhere on the body, made up of arteries, veins and thin, intervening vessels called capillaries through which the main exchange of oxygen, nutrients and waste products takes place. However, the vessels of the brain differ from others in one important respect – the so-called blood-brain barrier, which acts as a filter that blocks certain substances from passing through the vessel walls, thus protecting the brain from potentially toxic products while letting through whatever it needs for its structure and function. “It is becoming increasingly clear that a fully functional blood-brain barrier is essential to brain health and that a dysfunctional barrier is a factor of many brain diseases,” says study leader Christer Betsholtz, professor at Uppsala University and Karolinska Institutet's Department of Medicine, Huddinge. “The structure of the blood-brain barrier hasn’t been fully known, and so a detailed atlas of the brain’s vasculature and its barrier functionality is needed.” Cellular and molecular atlas Using a relatively new technique called single cell RNA sequencing, the researchers have produced a cellular and molecular atlas of the mouse brain vasculature. The blood vessels were broken apart in individual cells, which were then, one by one, mapped in accordance with their gene expression patterns and compared. The basic cell type and any gradual specialisations could then be ascertained for each cell. Finally, the molecular map was matched with the corresponding anatomy in tissue analyses using specific markers. “For the first time we’ve been able to show in detail how the blood-brain barrier differs among the various types of brain blood vessels,” says lead author Michael Vanlandewijck, assistant professor at Uppsala University and Karolinska Institutet and director of the Single Cell Analysis Unit at Karolinska Institutet’s and AstraZeneca’s Integrated Cardio Metabolic Centre (ICMC). It was long thought that the blood-brain barrier was made up of specialised endothelial cells in the blood vessels; the new study shows, however, that there are probably many other types of cells involved in the maintenance of the blood-brain barrier as well, including cells called pericytes in the capillary walls. The researchers were also able to establish the molecular identity of another cell type in the vascular wall, a kind of connective tissue cell located in a narrow space just outside the brain’s blood vessels. “This space has been posited to act as the brain’s lymph system, so it’ll now be incredibly interesting to study these cells further using the markers we’ve found,” says Dr Vanlandewijck. Links disease-causing genes to specific cell types The atlas means that a number of genes with known or presumed function in different brain diseases can now be associated with specific cell types in the brain’s vasculature. “We already have results indicating that many more cell types than previously thought are involved in neurovascular diseases such as Alzheimer’s and brain tumours,” says Professor Betsholtz. “We’re now able to study this systematically in different diseases with the same type of analyses as we’ve used here.” The study was conducted by researchers at Uppsala University and Karolinska Institutet and colleagues in France, Finland, Switzerland, Japan and China. It was financed by AstraZeneca, the Swedish Research Council, the European Research Council (ERC), the Leducq Foundation, the Swedish Cancer Society, the Knut and Alice Wallenberg Foundation, the Swedish Brain Fund, the Swiss National Science Foundation and the Synapsis Foundation. Publication A molecular atlas of cell types and zonation in the brain vasculature Michael Vanlandewijck, Liqun He, Maarja Andaloussi Mäe, Johanna Andrae, Koji Ando, Francesca Del Gaudio, Khayrun Nahar, Thibaud Lebouvier, Bàrbara Laviña, Leonor Gouveia, Ying Sun, Elisabeth Raschperger, Markus Räsänen, Yvette Zarb, Naoki Mochizuki, Annika Keller, Urban Lendahl, Christer Betsholtz Nature, online 14 February 2018. DOI: 10.1038/nature25739

Ewa Ehrenborg new Vice-Dean

Wed, 14/02/2018 - 16:36
Professor Ewa Ehrenborg has been appointed the new vice-dean for collaboration with Stockholm County Council (SLL), with a particular focus on education at Karolinska University Hospital. Radical changes are taking place in the healthcare field in Stockholm, changes that impact on KI. Karolinska University Hospital is being reorganised under a new business model and a large volume of outpatient care is being moved out. In order to make sure that high quality education can still be obtained at the hospital, KI created the office of vice-dean for collaboration with SLL, with a focus on education, in 2017. This year, this role has been assigned to Ewa Ehrenborg, professor of molecular cardiovascular medicine at the Department of Medicine, Solna. “The appointment is a very important one, especially in light of the consequence analysis of Karolinska University Hospital’s new business model that was done during my predecessor Carl-Fredrik Wahlgren’s time,” she says. The consequence analysis showed that action needs to be taken to ensure that students, especially medical students, can attain certain intended learning outcomes and degree objectives. There is now an agreement with concrete solutions on how to achieve this. Professor Ehrenborg will be putting her energies into monitoring progress. “A great deal of healthcare is moving out and the students need to be at local hospitals, academic specialist centres and so on, so that they can deal with patients with common and acute conditions and learn to independently diagnose and treat them.” Part of Professor Ehrenborg’s role is to make sure that education at KI maintains a high level of quality. To this end she will be working closely with, amongst other bodies, the various clinics and units at Karolinska University Hospital. “The hospital’s new business concept also creates new opportunities for learning that we want our students to enjoy.” Professor Ehrenborg was awarded KI’s Pedagogical Prize in 2017 for having developed interprofessional learning and student-activating teaching that integrate closely with the latest research. The office of vice-dean also includes ensuring the availability of teaching environments where students from different professions can learn from each other and together, as well as clinical training environments. The office of vice-dean is a temporary half-time position during 2018 and reports to the dean of education, Annika Östman Wernerson. “Ewa Ehrenborg is a doctor and a researcher with a wide contact network in education,” says Professor Östman Wernerson. “For many years, she’s been the director and coordinator of the Centre for Clinical Education, where she has worked hard to raised the quality of Work-Integrated Learning on our programmes. She’s therefore highly suited to the important office of vice-dean for collaboration.” Text: Ann Patmalnieks 

Professor Janne Lehtiö new Scientific Director of SciLifeLab

Wed, 14/02/2018 - 10:36
Karolinska Institutet has chosen a new Scientific Director for SciLifeLab, Sweden’s largest life science research centre. Professor Janne Lehtiö will act as a catalyst for collaboration between KI and SciLifeLab. Janne Lehtiö, professor in clinical proteomics at KI:s Department of Oncology-Pathology, has been appointed Scientific Director of SciLifeLab. The centre for molecular biosciences, a collaboration between host universities Karolinska Institutet (KI), KTH Royal Institute of Technology, Stockholm University and Uppsala University, develops advanced technologies for dissemination to researchers across the country.  The assignment includes acting as the representative for and coordinator of KI’s participation in the centre, as well as supporting management on issues related to SciLifeLab. Janne Lehtiö will be taking up the post with immediate effect. “It is exciting and important work. I hope that I can be a catalyst for collaboration between the various researchers. Hopefully, I will be able to contribute to two-way communication and mutual understanding. Researchers at KI must be made aware of how they can utilise the facilities. SciLifeLab is an important hub for technology-driven research, that can interact with basic and clinical research.” believes Janne Lehtiö. “It is extremely interesting to see this type of technology used in point-of-care clinical studies. In future, this may lead to improved individualised care for cancer patients. The post of Scientific Director is equivalent to 20% of a full-time position. Janne Lehtiö will continue to perform his ordinary duties in parallel with the new position. Since 2008, he has been the leader of a research group studying cancer and proteomics. “My own research deals with developing new methods for proteomics and applying these to individual cancer treatments. The primary focus is on lung and breast cancer and leukaemia, both in children and adults.” He is also director of Karolinska University Hospital’s clinical proteomics facility and is involved in the Swedish national infrastructure for biological mass spectrometry (BioMS), where Stockholm hosts the National Node for Proteogenomics and Chemical Proteomics.  Janne Lehtiö obtained an MSc in biochemistry at Helsinki University and a PhD in bioengineering at KTH. After defending his thesis, Janne worked in industry in the field of biomarker research. He also has experience of close collaboration with Karolinska University Hospital. Professor Karin Dahlman-Wright, KI’s pro-vice-chancellor, thinks along the same lines as Janne Lehtiö. “We must ensure that all KI researchers have sufficient knowledge of the technologies available at SciLifeLab. It is also important that  there are good lines of communication between KI’s management, SciLifeLab and the KI researchers working there,” she says. Karin Dahlman-Wright herself held the position of Scientific Director at SciLifeLab between 2013 and 2015. The position then remained unfilled, whereupon Professor Lars Engstrand took on the task during a transitional period.  “Lars Engstrand did an excellent job but it is now time for KI to seek a more long-term solution,” says Karin Dahlman Wright. “Janne Lehtiö’s broad technological and methodological expertise, combined with his long experience of managing infrastructure at local, regional and national level, makes him ideally suited to the task,” continues Karin Dahlman-Wright. “His close collaboration with clinical operations as director of the clinical proteomics core facility is an additional advantage.” She is now looking forward to Janne Lehtiö taking responsibility for increasing knowledge about the research carried out at SciLifeLab and how it can be applied to the healthcare sector. She emphasises the importance of SciLifeLab’s operations even outside of KI. “The government is investing heavily in SciLifeLab and it is vital that we make a broad impact across Sweden.” Text: Ann Patmalnieks

New method maps the dopamine system in Parkinson’s patients

Tue, 13/02/2018 - 14:53
With the aid of a PET camera, researchers from Karolinska Institutet have developed a new method for investigating the dopamine system in the brains of patients suffering from Parkinson’s disease. The method measures levels of a protein called dopamine transporter and could lead to improved diagnosis of Parkinson’s disease and the development of new treatments. The study is published in the scientific journal Movement Disorders. Dopamine is a substance produced in the brain and is responsible for controlling our movements. The cells that produce dopamine are located in an area known as the brainstem, from where dopamine is then secreted into the basal ganglia, an area of the brain that plays an important function in regulating our movements. In Parkinson’s disease, dopamine cells degenerate and their loss is responsible for the motor symptoms that characterise the disorder, such as shaking, slowness of movement and difficulty in walking. Measured the levels of DAT Using a special brain imaging technique known as Positron Emission Tomography (PET), a group of researchers at Karolinska Institutet have measured the levels of the dopamine transporter protein DAT that regulates the levels of dopamine in the brain. DAT functions as a biomarker for dopamine cells and is present on the surface of the dopamine cells in the cell bodies, on the nerve fibres and on the nerve endings. By measuring where DAT is found, researchers have been able to map the presence of dopamine cells. The study was based on 20 patients suffering from mild Parkinsonism and an equal number of healthy individuals. The results showed significantly lower amounts of DAT in nerve endings in the Parkinson’s patients than those not suffering from the disease. However, the amount of DAT remained relatively intact in cell bodies and nerve fibres. Still viable in early stages of the disease “These results suggest that in the early stages of the disease dopamine cells are still viable and that, given the correct treatment, it should be possible to restore their function,” says Andrea Varrone, senior lecturer in nuclear medicine at Karolinska Institutet’s Department of Clinical Neuroscience who led the study. “The method we have developed is likely to be able to assist in the diagnosis of Parkinson’s disease at an earlier stage and predict the development of the disease. DAT can also be used as a biomarker in clinical trials of new medicines and treatment strategies,” he continues. Future studies will examine patients with more advanced Parkinson’s, in order to gain a greater understanding of the links between DAT and clinical variables such as motor symptoms and the various stages of the disease. The study has been financed by the Swedish Research Council, AstraZeneca Translational Science Centre at Karolinska Institutet, the Swedish Foundation for Strategic Research and a private donation from Eira Larsson. The authors have not indicated any potential conflicts of interest. Publication “Nigrostriatal dopamine transporter availability in early Parkinson’s disease” Patrik Fazio, Per Svenningsson MD, Zsolt Cselényi, Christer Halldin, Lars Farde, Andrea Varrone Movement Disorders, online 13 February 2018, doi: 10.1002/mds.27316

This is how Academic Specialist Centre can attract researchers

Tue, 13/02/2018 - 09:33
In parallel with the introduction of highly specialised healthcare at the new Karolinska University Hospital Solna, and in certain respects a more problematic research and teaching environment, increasing attention has been focused on the Academic Specialist Centre. It is the hope of not only the vice-chancellor, but also politicians, that the newly opened centre will prove to be attractive to both researchers and students. “Today, we create bonds between Karolinska Institutet and Stockholm County Council,” says Sofia Ernestam, operations manager of the Academic Specialist Centre, which was officially opened on 7 February in front of around one hundred people at Solnavägen 1E. Here, three healthcare units – specialising in diabetes, neurology and rheumatology – will share premises that are in no way reminiscent of hospital environments. That being said, the Academic Specialist Centre is of course not a hospital, although chronically ill patients with selected diagnoses – diabetes, MS, Parkinson’s and rheumatological disorders – will receive specialist care here. The Academic Specialist Centre, a collaboration between Stockholm Health Care Services and Karolinska Institutet, is a part of the investment in future healthcare aimed at forging stronger links between research and development, education and healthcare. “The work we are doing is pioneering in how it links research and development to treatment. For example, some of the most cutting-edge treatments for MS are being conducted here,” says Ole Petter Ottersen, vice-chancellor of Karolinska Institutet, during the opening ceremony. A little while later, he explained why the Academic Specialist Centre is so important to KI: “We are witnessing a healthcare sector undergoing massive change. New Karolinska Solna has become increasingly highly specialised, we see more internet-based healthcare and research and education must keep pace. Here, we have a concentration of not only expertise but also patients. This means that researchers will be better able to follow patients here compared to when they were widely spread across the Stockholm region,” explained Ole Petter Ottersen. Among those attending the opening was Irene Svenonius, Moderate Party county councillor, who was of the opinion that the Academic Specialist Centre will be very important to patients and that, in all likelihood, the treatment of many chronic diseases will benefit from earlier access to research. “I believe that the centre will prove attractive to researchers, offering as it does increased access to point-of-care research. And when we see it working well, I think that the County Council will identify more areas in which this model can be applied,” she commented after the opening. Another idea behind the initiative is that patient’s will come to the centre at an early stage of their disease and be heavily involved in their own treatment. Even various patient organisations have been greatly involved in the Academic Specialist Centre. Making the Centre attractive to researchers and students is of course vital to ensuring the desired results. Sofia Ernestam believes that the large numbers of chronically sick patients available to practice on will undoubtedly attract students. “In order for research to be successfully carried out, it is important that the infrastructure works. As soon as the patient arrives, the receptionist will have the opportunity to ask if they would like to provide biobank samples. There are currently three daily runs to Karolinska University Laboratory and CMM. There will also be an opportunity for researchers to attend if they have research subjects who are patients at the clinic,” she says. Text: Maja Lundbäck

Letter to the Embassy of Iran regarding Ahmadreza Djalali

Thu, 08/02/2018 - 12:47
Amnesty International’s Swedish section, Karolinska Institutet and The Royal Swedish Academy of Sciences have sent a letter to Letter to the Iranian Ambassador, asking for a meeting to discuss the physician and researcher Ahmadreza Djalali. Ahmadreza Djalali was sentenced to death in October 2017 for alleged espionage on behalf of the Israeli government. Although Djalali is an Iranian citizen, he has a permanent residence permit in Sweden and was previously a researcher in disaster medicine at Karolinska Institutet, where he also defended his thesis in 2012. Read the letter to the Embassy of Islamic Republic of Iran.    

Apgar scores in neonates predict risk of CP and epilepsy

Thu, 08/02/2018 - 06:30
An infant’s scores on the so-called Apgar scale can predict the risk of a later diagnosis of cerebral palsy or epilepsy. The risk rises with decreasing  Apgar score, but even slightly lowered scores can be linked to a higher risk of these diagnoses, according to an extensive observational study by researchers at Karolinska Institutet published in The BMJ. “However, it’s important to remember that even if the relative risks are high, the absolute risks of CP and epilepsy are still small,” says researcher Martina Persson, paediatrician and associate professor at Karolinska Institutet’s Department of Medicine, Solna. “This means that most babies with very low Apgar scores do not develop CP or epilepsy”. Apgar is a point system routinely used at birth to assess a neonate’s vitality at one, five and ten minutes after birth. The scale ranges between 0 and 10, where a score of 10 indicates a baby in full health. It is well  known that a low Apgar score of between 0 and 6 points at one or five minutes after birth is linked to a higher risk of cerebral palsy (CP) and epilepsy, and that a very low score of between 0 and 3 points at ten minutes indicates a significantly higher risk of CP. However, no linear correlation has yet been confirmed and it is unclear whether even small changes on the scale at the different times affect the risk of neurological morbidity. Various national registers To interrogate this relationship, researchers at Karolinska Institutet analysed data from the national Medical Birth Registry for over 1.2 million babies without malformations born at full term between the years 1999 and 2012. The researchers identified children diagnosed with CP or epilepsy before the age of 16 in various national registers using diagnostic codes and then calculated the risk of CP and epilepsy for every Apgar level at five and ten minutes after birth and in relation to changes in Apgar score between ten and five minutes. A total of 1,221 babies (0.1 per cent) developed CP and the risk successively increased with decreasing scores at five minutes. Compared with infants with a top Apgar score (10) at five minutes, babies with a score of 9 had almost twice the risk of developing CP, while a score of 0 at five minutes was associated with a 280-fold risk. An even higher risk was noted for babies with similar Apgar scores at 10 minutes. A total of 3,975 babies (0.3 per cent) were diagnosed with epilepsy, and the risks of epilepsy increased with decreasing scores at five and ten minutes, although not as markedly as for CP. Small changes in score Even small changes in score between five and ten minutes after birth were shown to affect the risks. For example, babies with a score of 7/8 at five minutes and 9/10 at ten minutes had a higher risk of CP or epilepsy than babies with a score of 9/10 at both times. A higher risk of epilepsy was also observed in babies who scored a full 10 points at five minutes and then 9 at ten minutes compared to babies that had top scores at both times. “The results show that it’s important to evaluate neonate vitality at both five and ten minutes, even if the score is normal at five,” says Dr Persson. “We also need to work actively with the babies who do not score full Apgar points since it is likely to improve their prospects.” Some of the strengths of the study are that it was based on a large number of individuals and that the researchers were able to control for the many so-called confounders in their analyses. The researchers point out, however, that it was an observational study and that no definite conclusions about causality between Apgar score and the risk of neurological morbidity in babies can be drawn. The study was financed by several bodies, including the Swedish Research Council for Health, Working Life and Welfare (Forte), Stockholm County Council and Karolinska Institutet. Publication Five and 10 minute Apgar scores and risks of cerebral palsy and epilepsy: population based cohort study in Sweden Martina Persson, Neda Razaz, Kristina Tedroff, K.S. Joseph, Sven Cnattingius The BMJ, online 8 February 2018, doi: 10.1136/bmj.k207.

Researcher cleared of misconduct but does not escape criticism

Wed, 07/02/2018 - 14:45
On Tuesday, Karolinska Institutet’s vice-chancellor Ole Petter Ottersen reached the conclusion that the implementation of the clinical research study "Infusion av amniocyter från fosterhinna och liknande bindvävsstamceller vid vävnadsskada, blödning och/eller transplantat kontra värdreaktion" (Infusion of amniocytes from extraembryonic membranes and similar mesenchymal stem cells in cases of tissue damage, haemorrhage and/or graft-versus-host disease) and the research projects conducted during 2009-2017 did not constitute misconduct in research. However, the studies are criticised for flaws relating to research methodology and documentation. During the years 2011-2015, a clinical research study was conducted at Karolinska Institutet with the aim of improving the situation for patients who had been treated using stem cells from another person, and who had subsequently suffered from serious rejection reactions. In June 2015, questions were raised regarding patient safety and an inquiry was launched by Karolinska University Hospital, resulting in the cessation of the treatment. By then, 68 children and adults had been experimentally treated with decidual cells cultivated from donated placentas. On 11 April 2016, Karolinska Institutet’s acting vice-chancellor Karin Dahlman-Wright decided to begin an investigation into suspected misconduct in research. The researchers who participated in the study were Olle Ringdén, Mehmet Uzunel, Mats Remberger, Jonas Mattsson, Silvia Nava, Birgitta Omazic, Zuzana Potáková and Helen Kaipe, all of whom worked at Karolinska Institutet. In his decision, vice-chancellor Ole Petter Ottersen confirms that the research project had demonstrable shortcomings with regard to research methodology and documentation.  Karolinska Institutet, in common with the Expert Group on Misconduct in Research at the Central Ethical Review Board, finds that the requisite permits were in place from the Medical Products Agency, ethical review board and radiation protection committee. However, the confirmed flaws in the research mean that no authoritative data has been obtained. KI therefore finds Ole Ringdén to be culpable for the flaws in the implemented research, although not to such a degree as to constitute misconduct 

How exercise training promotes a sound mind in a sound body

Tue, 06/02/2018 - 18:05
A new study from Karolinska Institutet shows that the same mechanisms behind the beneficial effects of exercise training on the brain also help to counteract fat and to strengthen the immune system. The results, which are published in the journal Cell Metabolism, can ultimately give rise to new obesity and diabetes drugs. In 2014, researchers at Karolinska Institutet reported that they had discovered a mechanism behind the beneficial effect of exercise training on the brain. A follow-up study now demonstrates that the same process also boosts fat metabolism and strengthens the anti-inflammatory properties of the immune system. “We’ve linked the two parts of the expression ‘sound mind, sound body’,” says Jorge Ruas, principal investigator at the Department of Physiology and Pharmacology, Karolinska Institutet. “Our research adds to the understanding of why exercise training benefits the body and in the long run can lead to the development of new treatments for obesity or diabetes.” In the earlier study, the researchers were able to show that trained muscles help to clean the blood in a way similar to the kidneys and liver. Through exercise training, the muscles can convert the stress marker kynurenine into kynurenic acid. High levels of kynurenine have been measured in people with depression and mental illness. Fed on a fat-rich diet For this present study, the researchers further examined the function of kynurenic acid. Using mice fed on a fat-rich diet that made them overweight and raised their blood sugar levels, they found that a daily dose of kynurenic acid stopped the mice putting on weight and gave them better glucose tolerance, despite no change in their food intake. The researchers posit the explanation that kynurenic acid activated the cell receptor GPR35, which is found in both fat cells and immune cells. This led in the former to a conversion of white fat into energy-burning brown fat, and in the latter to an enhancement of their anti-inflammatory properties. “We’ve shown that kynurenic acid prevents weight gain despite excessive energy intake,” says Dr Ruas. “Our next step is to identify the complex chain of interacting molecules that’s affected by diet and training.” The study was financed by the Berth von Kantzow Foundation, the Diabetes Research & Wellness Foundation, the European Research Council, the Erling-Persson Family Foundation, Karolinska Institutet, the Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation, Skandia, the Stichting af Jochnick Foundation, the Swedish Diabetes Association, the Swedish Society for Medical Research and the Swedish Research Council. Publication Kynurenic acid and GPR35 regulate adipose tissue energy homeostasis and inflammation Leandro Z. Agudelo, Duarte M. S. Ferreira, Igor Cervenka, Galyna Bryzgalova, Shamim Dadvar, Paulo R. Jannig, Amanda T. Pettersson-Klein, Tadepally Lakshmikanth, Elahu G. Sustarsic, Margareta Porsmyr-Palmertz, Jorge C. Correia, Manizheh Izadi, Vicente Martínez-Redondo, Per M. Ueland, Øivind Midttun, Zachary Gerhart-Hines, Petter Brodin, Teresa Pereira, Per-Olof Berggren, and Jorge L. Ruas Cell Metabolism, online 6 February 2018, DOI: https://doi.org/10.1016/j.cmet.2018.01.004

Calcium-transfer may open up to new ways of treating Alzheimer's disease

Tue, 06/02/2018 - 17:55
Hello Maria Ankarcrona, Alzheimer's Researcher at the Division of Neurogeriatrics. Recently the reputable scientific journal Current Biology published one of your studies, what is it about? "A cell has several constituents, one of which is mitochondria. They produce energy in the cell and are also important for regulation of cell death, production of fatty acids and calcium levels. In this paper we show a new role of the mitochondrial protein TOM70 (translocase of the outer membrane 70). We report that TOM70 interacts with IP3R3 (inositol 1,4,5-triphosphate receptor 3) sustaining cell bioenergetics". Which are the most important results, and what new knowledge does the paper add?  "For the first time, we show that TOM70 acts as a modulator of calcium-transfer between endoplasmic reticulum (ER) and mitochondria at specific contact points between these two organelles, also known as mitochondria-associated membranes (MAM). We also show that TOM70 clusters at ER-mitochondria contact sites and interacts with IP3R3, a regulator of ER calcium release. Upon deletion of TOM70, IP3R3s translocate out from these subcellular hubs resulting in decreased calcium transfer from ER to mitochondria. Our data show that the decrease in calcium shuttling affects mitochondrial activity, cell proliferation and autophagy". How can this new knowledge contribute to improving human health? "The discovery that TOM70 depletion affects cell bioenergetics suggests that modulation of TOM70 expression or activity could be a promising pharmacological target.  It is known that the ER-mitochondria interplay is affected in multiple diseases. Here we show that depletion of TOM70 selectively affects the shuttling of calcium between ER and mitochondria, while the physical contacts between the two organelles are unchanged.  These findings open up a novel approach to pharmacologically modulate MAM-function and calcium transfer which would be potentially beneficial in the treatment of a wide-range of pathologies associated with alteration in mitochondria ER contact sites, such as Alzheimer’s disease". The publication TOM70 sustains cell bioenergetics by promoting IP3R3-mediated ER to mitochondria Ca2+ transfer Riccardo Filadi, Nuno Santos Leal, Bernadette Schreiner, Alice Rossi, Giacomo Dentoni, Catarina Moreira Pinho, Birgitta Wiehager, Domenico Cieri, Tito Calì, Paola Pizzo, Maria Ankarcrona Current Biology, 5 februari 2018

Asthma drug potential treatment for aortic aneurysm

Tue, 06/02/2018 - 08:00
Aortic aneurysm – the dilation of the aorta – is a serious condition that lacks effective drug treatment. Researchers at Karolinska Institutet report in the journal PNAS, however, that a common asthma drug can retard the development of aortic aneurysm in mice. ­“Our results are exciting and open the way for a medical treatment of this serious vascular disease,” says Professor Jesper Z. Haeggström at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics. An aortic aneurysm occurs when the wall of the body’s largest artery, the aorta, weakens and swells. The disease progresses slowly and affects some 5 per cent of men and 1 per cent of women over the age of 60. The condition is largely symptom-free and is normally therefore not discovered until late in its development when it threatens to rupture and cause life-threatening haemorrhaging. There are currently no drugs for preventing and treating aortic aneurysm. In earlier studies, the research group found high levels of particular inflammatory signal substances called leukotrienes in the vascular walls of patients operated on for aortic aneurysm. Leukotrienes drive inflammation and are known for their potential to cause asthma. Since the asthma drug montelukast blocks leukotrienes, the team decided to examine whether it could also have an effect on aortic aneurysm. Very few side-effects Their studies on mice revealed that the treatment did indeed reduce the swelling of the aorta and reduced levels of an enzyme that can break down the vascular wall and a protein involved in inflammatory processes. “This study is particularly interesting from a therapeutic perspective since montelukast is a safe drug with very few side-effects, which means it can be taken over a long period of time,” explains Professor Haeggström. “In the study we used drug doses equivalent to those used in the treatment of asthma patients.” The researchers hope to be able to start a controlled clinical trial to test the drug’s efficacy on patients with aortic aneurysm. The study was conducted with researchers at Linköping University and the Technical University of Munich, Germany and financed by the Swedish Research Council, Stockholm County Council, the Novo Nordisk Foundation, the Heart and Lung Foundation, the Ragnar Söderberg Foundation, Karolinska Institutet and the European Research Council (ERC). Publication Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aortic aneurysm Antonio Di Gennaro, Ana Araujo, Albert Busch, Hong Jin, Dick Wågsäter, Emina Vorkapic, Kenneth Caidahl, Per Eriksson, Bengt Samuelsson, Lars Maegdefessel, Jesper Z. Haeggström PNAS, online the week of 5-9 February 2018.

Prince William and Kate Middleton visit KI – focus on mental health in adolescents

Wed, 31/01/2018 - 13:25
During their visit to Sweden and Stockholm in the company of Crown Princess Victoria and Prince Daniel, Prince William and Kate Middleton specifically requested to learn more about the Youth Aware of Mental Health (YAM) Programme and the work being carried out at the National Centre for Suicide Research and Prevention of Mental Ill-Health at Karolinska Institutet. The royal couple were also keen to learn more about research being carried out at Karolinska Institutet into physical activity and its prophylactic effects. The Duke and Duchess have a history of involvement in issues related to mental illness among children and young people in general, and suicide prevention in particular. During their visit to Karolinska Institutet Prince William and Kate Middleton met Danuta Wasserman, professor of psychiatry and suicidology and Carl Johan Sundberg, professor of molecular and applied exercise physiology, as well as vice-chancellor Ole Petter Ottersen. The couple were informed about the YAM model and listened to a presentation by KI researchers about the effects of physical activity on young people’s mental health and cognitive functions. Another issue discussed was the connection between the ever-increasing use of smartphones and increased levels of mental illness in children and young people. After visiting Karolinska Institutet, the Duke and Duchess continued on to Matteusskolan, a school in Stockholm, to meet pupils and teachers who have participated in the YAM Programme. Together with the Swedish royal couple and Swedish Minister for Education Gustav Fridolin, they participated in role-play exercises that form part of the YAM programme. “The royal couple expressed a desire to participate personally to see how it feels,” says Danuta Wasserman. “They were quite clear in their wish to contribute to young people being able to discuss mental health. As a medic, it is pleasing to me that young people today are interested in all aspects affecting mental health, including the biological, and how lifestyles affect the brain’s functions.” Prince William and Kate Middleton have previously spoken about their own experiences of suicide, depression and mental illness. In his previous role as an ambulance pilot, the Prince came into contact with many young people with suicidal thoughts. The YAM Programme was created within the EU project SEYLE, and combines role play with discussions on mental health based on young people sharing their own experiences under the guidance of two experienced instructors who always remain in the classroom. The programme is designed to teach young people about what they can do to affect their own psychological wellbeing, including how this is affected by eating habits, physical activity and sleep. Using a randomised controlled study of 11,000 teenagers from 168 schools in 10 European countries, published in The Lancet, researchers were able to show that the risk of suicide among young people who were involved in the YAM Programme was half that of a control group. The project has also produced a comprehensive database of facts relating to mental health among young people, for example it revealed that 29% of those involved in the study had minor symptoms of depression. Even if suicide continues to be the single greatest cause of death among the 16-29 age group in Sweden, there are signs of a long-term decline in the number of suicides over several decades. Behind this decline lies not only improved diagnosis and treatment of depression, but also a general increase in awareness regarding the problem. “If one begins to discuss a problem, it is almost always a step towards alleviating it,” says Danuta Wasserman. “The greatest contribution of the YAM Programme is preventative but, as we distribute questionnaires to all pupils, we are also able to catch those who are already in a situation where they need help.”

Researchers found guilty of scientific misconduct

Tue, 30/01/2018 - 13:41
On Tuesday, Karolinska Institutet’s vice-chancellor Ole Petter Ottersen reached the decision to find Paolo Macchiarini, Philipp Jungebluth, Bernhard Holzgraefe and Håkan Kalzén guilty of scientific misconduct. The case relates to the article “Autologous peripheral blood mononuclear cells as treatment in refractory acute respiratory distress syndrome”, published in 2015 in Respiration. The article is a case study of a patient suffering from acute lung damage who, in 2011, received ECMO treatment at Karolinska University Hospital and thereafter experimental treatment. On 22 April 2016, then acting vice-chancellor Karin Dahlman-Wright decided to initiate an inquiry into suspected scientific misconduct due to concerns expressed to KI regarding the article. According to the Swedish Higher Education Ordinance, universities are required to investigate suspected scientific misconduct and, during such an inquiry, may obtain an opinion from the Expert Group for Misconduct in Research at the Central Ethical Review Board, something that was done in the case in question. According to the Vice-Chancellor’s decision, Respiration should be notified with a request that the article be immediately withdrawn. None of the researchers who have been found guilty of scientific misconduct are employed by Karolinska Institutet and therefore they will not be subject to any disciplinary measures under employment legislation. A decision is expected from the Vice-Chancellor in the spring regarding scientific misconduct relating to six articles of which Paolo Macchiarini was the main author. These include an article published in The Lancet describing the transplantation of a synthetic prosthesis into human trachea.

Oestrogen causes neuroblastoma cells to mature into neurons

Mon, 29/01/2018 - 10:04
The female sex hormone oestrogen can perform an important role in neuroblastoma, a form of cancer mainly affecting young children. In laboratory experiments, researchers at Karolinska Institutet demonstrate that oestrogen treatment and overexpression of the oestrogen receptor cause malignant neuroblastoma cells to mature into neuron-like cells. The study, which is published in PNAS, gives hope of new treatment possibilities. Neuroblastoma forms in the peripheral nervous system and is one of the most common forms of solid cancer in young children. The disease mainly affects babies and young children, and while in some cases the tumours can disappear of their own accord, the majority are aggressive, metastasising cancer tumours that are resistant to modern combinations of surgery, radiotherapy and intensive chemotherapy. The most aggressive forms of neuroblastoma are often associated with a more active MYCN gene, which drives tumour cell growth and spread and inhibits the maturation of the cells. A possible target for new drugs “Our research focuses particularly on the activity of this gene and how it relates to neuroblastoma,” says Professor Marie Arsenian-Henriksson at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet. “MYCN is often seen only as a marker for a poor prognosis, but it’s critical to the disease and is a possible target for new drugs.” In a previous study, her group discovered that activation of MYCN results in the formation of specific microRNAs, which are relatively small RNA molecules that regulate proteins. Some of these microRNAs disable the oestrogen receptor ERalpha. The present study shows that the inhibition of these microRNA molecules or oestrogen therapy in combination with an overexpression of the oestrogen receptor can cause aggressive neuroblastoma cells with MYCN activation to mature into neuron-like cells which behave more like normal cells. Studied human and mouse tissue The researchers studied tumour tissue from patients, cultivated human tumour cells and tumours in mouse models for neuroblastoma. In the mice, the neuron-like cells did not grow as quickly as the original cancer cells, and analyses of the tumour tissue from patients show that those with a high level of the oestrogen receptor have a better survival rate that those with a low. “Our data suggests that oestrogen could be a therapeutic method for patients who express high levels of the oestrogen receptor,” continues Professor Arsenian-Henriksson. “Another possible therapy could involve deregulating MYCN or upregulating the oestrogen receptor and then treating with oestrogen. We have previously shown that the deregulation of MYCN leads to a high expression of the oestrogen receptor.” The study was financed by the Lars Hierta Memorial Foundation, the Mary Béve Foundation for Childhood Cancer Research, the Anna-Brita and Bo Castegren Memorial Foundation, the Swedish Cancer Society, the Swedish Research Council, the Swedish Childhood Cancer Foundation, the King  Gustaf V’s Jubilee Fund and Karolinska Institutet. Publication “MYCN-amplified neuroblastoma maintains an aggressive and undifferentiated phenotype by deregulation of estrogen and NGF signaling” Johanna Dzieran, Aida Rodriguez Garcia, Ulrica Kristina Westermark, Aine Brigette Henley, Elena Eyre Sánchez, Catarina Träger, Henrik Johan Johansson, Janne Lehtiö, Marie Arsenian-Henriksson Proceedings of the National Academy of Sciences, online 26 January 2018

Master’s students at KI at risk of deportation

Fri, 26/01/2018 - 14:46
A master’s student from China who has paid tuition fees for her education at Karolinska Institutet has been denied a renewed residence permit for her fourth and final term. The Swedish Migration Agency considers that the student cannot prove that she can support herself and therefore has to leave the country within four weeks. “The situation for third-country guest students has changed dramatically since tuition fees were introduced. The rules for residence permits now need to be adapted so that paying students with approved academic results can be granted a residence permit for the whole of the study period,” says Per Bengtsson, University Director at KI. Since the autumn of 2017 around ten master's students at Karolinska Institutet (KI) from non-EU countries have received deportation notices. Most have appealed to the Migration Court of Appeal but some are still waiting for a decision. The student who is now being deported has had her request to have her case reviewed by the Migration Court of Appeal refused. The question now is how the student will be able to complete her studies that she has already paid for. “The situation has huge consequences, first and foremost for the affected students but also for KI’s and other educational institutions’ ability to attract international students and contribute to Sweden’s reputation as a leading knowledge nation,” Per Bengtsson continues. In order to be granted a residence permit in Sweden the students, according to the Swedish Migration Agency's rules, need to be able to demonstrate that they have their own personal funds or, for example, through scholarships, to cover their living costs of SEK 8,064 a month for ten months. The Migration Agency’s reason for its refusal is that the students have not been able to prove that they have their own means of support to the required extent. So despite the students’ bank statements where money was available for their support, the Migration Agency considered that it is not credible that the funds are for them, but only temporarily deposited in the accounts. “These students are usually supported by their parents or other relatives, which is natural because it is unusual for young people to have personal assets equivalent to between 500,000 and 600,000 kronor, which is the total cost for a student from a non-EU country to study a master’s programme at KI,” says Per Bengtsson. KI has written to the Migration Agency and the Ministry of Education and Research about the matter and is working with other universities and the Swedish Institute to achieve a solution to the question of residence permits for studies. FACTS about tuition fees The Ordinance (2010:543) on application fees and tuition fees at higher education institutions for students from outside the EU/EEA came into effect on 1 July 2010. The ordinance was applied for the first time on 1 August 2011. The term fee to study on one of the university's 9 global master’s programmes is about 90,000 kronor.

Graphene oxide is ‘sensed’ by specialised immune cells

Fri, 26/01/2018 - 09:04
A study by researchers at Karolinska Institutet, the University of Manchester and Chalmers University of Technology published in CHEM shows that our immune system handles graphene oxide (GO) in a manner similar to pathogens, paving the way for safer biomedical applications of this two-dimensional material. Graphene is the thinnest material known to man, a million times thinner than a human hair. Graphene oxide (GO), in turn, is an atomically thin material consisting only of carbon and oxygen atoms. GO is currently being considered for numerous uses including drug delivery and other medical applications. However, it is of critical importance to understand how these materials interact with the body. In a new study led by Professor Bengt Fadeel at the Institute of Environmental Medicine, Karolinska Institutet, it is shown that neutrophils, the most common type of white blood cell that is specialised in combating infections, release so-called neutrophil extracellular traps (NETs) when encountering GO. NETs are made up of a “spider-web” of DNA decorated with proteins that help neutrophils to destroy microorganisms such as bacteria and fungi. The researchers found that GO causes specific changes in the lipid composition of the cell membrane of neutrophils leading to the release of NETs. They could also show that antioxidant treatment reversed this process. In a companion study published in Nanoscale, it was shown that GO is degraded in NETs, much like bacteria and other pathogens. Part of the Graphene Flagship Project “Taken together, these studies show that GO can be trapped and degraded in NETs just like pathogens. Understanding how the immune system senses and handles GO paves the way for safer biomedical applications of GO and other graphene-based materials, for instance in the context of drug delivery”, says Professor Bengt Fadeel. The current study, performed at Karolinska Institutet in collaboration with Professor Kostas Kostarelos at the National Graphene Institute, University of Manchester, and the National Center of Imaging Mass Spectrometry at Chalmers University of Technology, is part of the EU's largest research initiative, the Graphene Flagship Project which has over 150 academic and industrial partners and a total budget of €1 billion. The research was funded by the European Commission through the Graphene Flagship Project, and the Swedish Research Council. Publication “Graphene Oxide Elicits Membrane Lipid Changes and Neutrophil Extracellular Trap Formation” Mukherjee SP, Lazzaretto B, Hultenby K, Newman L, Rodrigues AF, Lozano N, Kostarelos K, Malmberg P, Fadeel B Chem-Cell Press, online January 25, 2018, doi: 10.1016/j.chempr.2017.12.017, February 8, issue 4, pp 1-25

Everyday exercise has surprisingly positive health benefits

Thu, 25/01/2018 - 11:34
The benefits of low-intensity physical activity, such as standing, walking or doing household chores, can be more health beneficial than once thought. According to a study from Karolinska Institutet published in the journal Clinical Epidemiology, replacing half an hour’s sedentariness a day with everyday activity reduces the risk of fatal cardiovascular disease by 24 per cent. Cardiovascular diseases are the primary cause of death in Sweden, and while it is known that moderate to intense physical activity reduces the risk of cardiovascular disease, the benefits of low-intensity activity have yet to be agreed upon. For the present study, the researchers analysed how different levels of physical activity in 1,200 people across Sweden affected the mortality rate due to cardiovascular disease (amongst other causes) 15 years later. Data were gathered from the ABC (Attitude, Behaviour and Change) study, in which the activity level of the participants is measured using motion trackers, and compared them with data on deaths and causes of death from Swedish registries. Objective measures of physical activity “This is a unique study, since we’ve been able to analyse a large number of people with objective measures of physical activity for up to 15 years,” says study leader Maria Hagströmer, senior lecturer at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society. “Previous studies asked participants about levels of physical activity, but this can lead to reporting error since it’s hard to remember exactly for how long one has been sitting and moving around.” The study shows that there are considerable health benefits to be gained not only from moderate or intense physical activity but also from low-intensity (everyday) activity. Replacing half an hour’s sedentariness a day with such low-level activity can reduce the risk of dying from cardiovascular disease by an estimated 24 per cent. The more the better Replacing sedentariness with physical activity of at least moderate level equivalent to a brisk walk, or higher intensity training, had, as expected, an even greater effect on cardiovascular-related mortality. Ten minutes of moderate to intense activity a day reduced the risk of death due to cardiovascular disease by 38 per cent, 30 minutes a day by a full 77 per cent, according to their calculations. The study adjusted for other potential confounding factors, such as age, sex, smoking habits, educational level and previous morbidity. “In an earlier study, we also showed that people who sit still for more than 10 hours a day have a 2.5 times higher risk of early death than people who sit for less than 6.5 hours a day,” says first author Ing-Mari Dohrn, postdoc at Karolinska Institutet’s Department of Neurobiology, Care Sciences and Society. External funding for the study was obtained from insurance company Folksam. The ABC study was financed by Stockholm County Council, the Swedish Research Council for Sport Science and the EU-financed ALPHA (Assessing Levels of PHysical Activity) project. Publication “Replacing sedentary time with physical activity – a 15 year follow-up of mortality in a national cohort” Ing-Mari Dohrn, Lydia Kwak, Pekka Oja, Michael Sjöström, Maria Hagströmer Clinical Epidemiology, online 25 January 2018

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