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Researchers at Turku Centre for Biotechnology have invented new tools for decoding and controlling signalling circuits in living cells with flashes of light. In principle, any cellular circuit can now be targeted with the new method. By using this approach, the researchers discovered that major biological signalling circuits can be made to resonate when driven at their resonant frequency. Resonance is a familiar concept in music, physics and engineering and underlies technical approaches in chemistry, biology and medicine. - Our discovery that signalling circuits of mammalian cells can made to resonate is new and likely to have a relevance in the treatment of diseases. With this method we can control when the signalling pathway is on or off, says Senior Researcher Michael Courtney from Turku Centre for Biotechnology at the University of Turku and Åbo Akademi University, Finland. The team developed optogenetic inhibitors for protein kinases such as JNK which is a central regulator of cell function. - JNK protein in the cell cytoplasm was not thought to regulate gene expression in the nucleus and continuous inhibition in the cytoplasm is ineffective. However, the team found that delivering a specific frequency of inhibition pulses to JNK in the cytoplasm drove inhibition of gene expression in the nucleus. This indicates that cell signalling circuits can be controlled in previously unforeseen ways once the appropriate time-code has been identified, says Courtney. He explains that not only might cell circuit resonance play an unexpected role in degenerative disease processes, but it could even guide the discovery of new therapeutic approaches. Interestingly, the only previous report on cell circuit resonance in the scientific literature showed it can be used to prevent microbial cells from growing. This new discovery of similar behaviour in mammalian cells suggests it could potentially be used to stop cancer cells from growing. - Currently, the development of resistance to new drugs is a major problem in cancer, as it cost billions of dollars to develop and approve new drugs, and yet they can rapidly become ineffective as a treatment. With this new research information, we can perhaps change the frequency instead of using the same drug and in this way achieve a better outcome, says Courtney. The research team's newly discovered phenomenon of circuit resonance in mammalian cells might offer a way to avoid or work around drug resistance. The researchers have now assembled a research consortium which has applied for funding in order to begin the evaluation of this idea. The team started developing light-regulated tools while at the University of Eastern Finland. The project was funded primarily by the Academy of Finland's Photonics programme. The mammalian circuit resonance was discovered and characterised by the team after moving to the University of Turku. The team received support from the Turku BioImaging Screening Unit and funding from the National Cancer Institute in the Uniteds States, the EU-Marie Skłodowska-Curie programme, and Finnish foundations including the Magnus Ehrnrooth, Alfred Koredelin, Instrumentarium and Orion Foundations. This work was published in the Nature Communications journal on 12 May 2017. More information: Senior Researcher Michael Courtney, University of Turku, Turku Centre for Biotechnology, tel. +358 (0)504649827 , e-mail miccou@utu.fi


Researchers at Turku Centre for Biotechnology have invented new tools for decoding and controlling signalling circuits in living cells with flashes of light. In principle, any cellular circuit can now be targeted with the new method. By using this approach, the researchers discovered that major biological signalling circuits can be made to resonate when driven at their resonant frequency. Resonance is a familiar concept in music, physics and engineering and underlies technical approaches in chemistry, biology and medicine. "Our discovery that signalling circuits of mammalian cells can made to resonate is new and likely to have a relevance in the treatment of diseases. With this method we can control when the signalling pathway is on or off," says Senior Researcher Michael Courtney from Turku Centre for Biotechnology at the University of Turku and Åbo Akademi University, Finland. The team developed optogenetic inhibitors for protein kinases such as JNK which is a central regulator of cell function. "JNK protein in the cell cytoplasm was not thought to regulate gene expression in the nucleus and we thought that continuous inhibition in the cytoplasm is ineffective. However, the team found that delivering a specific frequency of inhibition pulses to JNK in the cytoplasm drove inhibition of gene expression in the nucleus. This indicates that cell signalling circuits can be controlled in previously unforeseen ways once the appropriate time-code has been identified," says Courtney. He explains that not only might cell circuit resonance play an unexpected role in degenerative disease processes, but it could even guide the discovery of new therapeutic approaches. Interestingly, the only previous report on cell circuit resonance in the scientific literature showed it can be used to prevent microbial cells from growing. This new discovery of similar behaviour in mammalian cells suggests it could potentially be used to stop cancer cells from growing. "Currently, the development of resistance to new drugs is a major problem in cancer, as it cost billions of dollars to develop and approve new drugs, and yet they can rapidly become ineffective as a treatment. With this new research information, we can perhaps change the frequency instead of using the same drug and in this way achieve a better outcome," says Courtney. The research team's newly discovered phenomenon of circuit resonance in mammalian cells might offer a way to avoid or work around drug resistance. The researchers have now assembled a research consortium which has applied for funding in order to begin the evaluation of this idea. The team started developing light-regulated tools while at the University of Eastern Finland. The project was funded primarily by the Academy of Finland's Photonics programme. The mammalian circuit resonance was discovered and characterised by the team after moving to the University of Turku. The team received support from the Turku BioImaging and funding from the National Cancer Institute in the Uniteds States, the EU-Marie Skłodowska Curie programme, and Finnish foundations including the Magnus Ehrnrooth, Alfred Koredelin, Instrumentarium and Orion Foundations. This work was published in the Nature Communications journal on 12 May 2017.


News Article | May 16, 2017
Site: phys.org

Cohort after cohort, fishing typically removes large fish from the population and can lead to rapid evolutionary changes in exploited fish populations. A new study from the University of Turku, Finland, shows that removing the largest individuals from the population can lead to massive gene expression changes in an experimentally exploited fish population. The study was funded by the Academy of Finland. During the last two decades, there has been a lot of discussion on size-selective fishing causing genetic changes in exploited populations in contemporary timescales. Now, researchers have shown that fishing can cause expression changes in thousands of genes and that these changes can at least partly be associated with changes at DNA level. "Removing the largest individuals from the experimentally exploited populations induced differences in the expression of more than 4,000 genes after five generations of size-selective harvesting," says postdoctoral researcher Silva Uusi-Heikkilä from the University of Turku. The harvesting experiment was done in collaboration between the University of Turku and the Leibniz Institute of Freshwater Ecology and Inland Fisheries, Berlin. For five generations, experimental zebrafish populations were harvested by using two harvesting strategies: removing the largest individuals and removing individuals randomly with respect to body size. After harvesting, the populations were allowed to recover for six generations. "Changes in gene expression help fish to adapt to different selective pressure," Uusi-Heikkilä says. "It's noteworthy, however, that the differences in expression pattern between the harvest treatments remained after the recovery." In addition to the changes in gene expression, the expression variance was also affected by fishing: fishing decreased the variance. Gene expression variation can be important because it may help fish to adapt to changes in the environment and the climate. "After the recovery period, the gene expression variance increased but only in randomly harvested fish. The variance continued to decrease among fish where the largest individuals had been removed," Uusi-Heikkilä says. Reduced variation caused by size-selective harvesting in exploited populations can slow down the recovery. "Moderate fishing pressure combined with protection of large individuals may advance the recovery of fish populations." More information: Silva Uusi-Heikkilä et al. Rapid, broad-scale gene expression evolution in experimentally harvested fish populations, Molecular Ecology (2017). DOI: 10.1111/mec.14179


News Article | May 16, 2017
Site: www.eurekalert.org

Cohort after cohort, fishing typically removes large fish from the population and can lead to rapid evolutionary changes in exploited fish populations. A new study from the University of Turku, Finland, shows that removing the largest individuals from the population can lead to massive gene expression changes in an experimentally exploited fish population. The study was funded by the Academy of Finland. During the last two decades, there has been a lot of discussion on size-selective fishing causing genetic changes in exploited populations in contemporary timescales. Now, researchers have shown that fishing can cause expression changes in thousands of genes and that these changes can at least partly be associated with changes at DNA level. "Removing the largest individuals from the experimentally exploited populations induced differences in the expression of more than 4,000 genes after five generations of size-selective harvesting," says postdoctoral researcher Silva Uusi-Heikkilä from the University of Turku. The harvesting experiment was done in collaboration between the University of Turku and the Leibniz Institute of Freshwater Ecology and Inland Fisheries, Berlin. For five generations, experimental zebrafish populations were harvested by using two harvesting strategies: removing the largest individuals and removing individuals randomly with respect to body size. After harvesting, the populations were allowed to recover for six generations. "Changes in gene expression help fish to adapt to different selective pressure," Uusi-Heikkilä says. "It's noteworthy, however, that the differences in expression pattern between the harvest treatments remained after the recovery." In addition to the changes in gene expression, the expression variance was also affected by fishing: fishing decreased the variance. Gene expression variation can be important because it may help fish to adapt to changes in the environment and the climate. "After the recovery period, the gene expression variance increased but only in randomly harvested fish. The variance continued to decrease among fish where the largest individuals had been removed," Uusi-Heikkilä says. Reduced variation caused by size-selective harvesting in exploited populations can slow down the recovery. "Moderate fishing pressure combined with protection of large individuals may advance the recovery of fish populations."


News Article | May 16, 2017
Site: www.sciencedaily.com

Cohort after cohort, fishing typically removes large fish from the population and can lead to rapid evolutionary changes in exploited fish populations. A new study from the University of Turku, Finland, shows that removing the largest individuals from the population can lead to massive gene expression changes in an experimentally exploited fish population. The study was funded by the Academy of Finland. During the last two decades, there has been a lot of discussion on size-selective fishing causing genetic changes in exploited populations in contemporary timescales. Now, researchers have shown that fishing can cause expression changes in thousands of genes and that these changes can at least partly be associated with changes at DNA level. "Removing the largest individuals from the experimentally exploited populations induced differences in the expression of more than 4,000 genes after five generations of size-selective harvesting," says postdoctoral researcher Silva Uusi-Heikkilä from the University of Turku. The harvesting experiment was done in collaboration between the University of Turku and the Leibniz Institute of Freshwater Ecology and Inland Fisheries, Berlin. For five generations, experimental zebrafish populations were harvested by using two harvesting strategies: removing the largest individuals and removing individuals randomly with respect to body size. After harvesting, the populations were allowed to recover for six generations. "Changes in gene expression help fish to adapt to different selective pressure," Uusi-Heikkilä says. "It's noteworthy, however, that the differences in expression pattern between the harvest treatments remained after the recovery." In addition to the changes in gene expression, the expression variance was also affected by fishing: fishing decreased the variance. Gene expression variation can be important because it may help fish to adapt to changes in the environment and the climate. "After the recovery period, the gene expression variance increased but only in randomly harvested fish. The variance continued to decrease among fish where the largest individuals had been removed," Uusi-Heikkilä says. Reduced variation caused by size-selective harvesting in exploited populations can slow down the recovery. "Moderate fishing pressure combined with protection of large individuals may advance the recovery of fish populations."


News Article | May 29, 2017
Site: www.sciencedaily.com

Body- and sex related problems constitute a distinct group of psychological ailments that is most common in middle aged women, according to scientific research. The project was financed by the Academy of Finland. A recent study shows that psychological problems relating to one's body and sexuality, such as body dissatisfaction, disordered eating, or sexual distress, are linked to each other but not strongly linked to externalizing -- such as aggression or substance abuse -- or internalizing -- such as anxiety or depressive symptoms. Women reported more psychological problems related to their body and sexuality than men. Using data from 13,000 adult women and men in Finland, researchers at the Department of Psychology at Åbo Akademi University have discovered that body- and sex related symptoms are not expressions of internalizing or externalizing disorders, as was earlier believed. Comparing the levels of symptoms across gender and age groups, middle age women reported higher levels of body- and sex related problems. The result of the study, published online in PLoS One, can inform further research on diagnostics and treatment of psychological disorders.


News Article | May 4, 2017
Site: www.eurekalert.org

A new study in Science from Karolinska Institutet maps out how different DNA-binding proteins in human cells react to certain biochemical modifications of the DNA molecule. The scientists report that some 'master' regulatory proteins can activate regions of the genome that are normally inactive due to epigenetic changes. Their findings contribute to a better understanding of gene regulation, embryonic development and the processes leading to diseases such as cancer. The DNA molecule carries information in the form of a sequence of four nucleotide bases, adenine (A), cytosine (C), guanine (G) and thymine (T), which can be thought of as the letters of the genomic language. Short sequences of the letters form 'DNA words' that determine when and where proteins are made in the body. Almost all of the cells in the human body contain the letters in precisely the same order. Different genes are however active (expressed) in different cell types, allowing the cells to function in their specialised roles, for example as a brain cell or a muscle cell. The key to this gene regulation lies in specialised DNA-binding proteins -- transcription factors -- that bind to the sequences and activate or repress gene activity. The DNA letter C exists in two forms, cytosine and methylcytosine, which can be thought of as the same letter with and without an accent (C and Ç). Methylation of DNA bases is a type of epigenetic modification, a biochemical change in the genome that does not alter the DNA sequence. The two variants of C have no effect on the kind of proteins that can be made, but they can have a major influence on when and where the proteins are produced. Previous research has shown that genomic regions where C is methylated are commonly inactive, and that many transcription factors are unable to bind to sequences that contain the methylated Ç. By analysing hundreds of different human transcription factors, researchers at Karolinska Institutet in Sweden have now found that certain transcription factors actually prefer the methylated Ç. These include transcription factors that are important in embryonic development, and for the development of prostate and colorectal cancers. "The results suggest that such 'master' regulatory factors could activate regions of the genome that are normally inactive, leading to the formation of organs during development, or the initiation of pathological changes in cells that lead to diseases such as cancer", says Professor Jussi Taipale at Karolinska Institutet's Department of Medical Biochemistry and Biophysics who led the research. The results pave the way for cracking the genetic code that controls the expression of genes, and will have broad implications for the understanding of development and disease. The availability of genomic information relevant to disease is expanding at an exponentially increasing rate. "This study identifies how the modification of the DNA structure affects the binding of transcription factors, and this increases our understanding of how genes are regulated in cells and further aids us in deciphering the grammar written into DNA", says Professor Taipale. The study was supported by the Academy of Finland Center of Excellence in Cancer Genetics and the ERA SynBio project MirrorBio, Karolinska Institutet's Center for Innovative Medicine, Knut and Alice Wallenberg Foundation, Göran Gustafsson Foundation, and the Swedish Research Council. Publication: Yimeng Yin, Ekaterina Morgunova, Arttu Jolma, Eevi Kaasinen, Biswajyoti Sahu, Syed Khund-Sayeed, Pratyush K. Das, Teemu Kivioja, Kashyap Dave, Fan Zhong, Kazuhiro R. Nitta, Minna Taipale, Alexander Popov, Paul A. Ginno, Silvia Domcke, Jian Yan, Dirk Schübeler, Charles Vinson, and Jussi Taipale. 'Impact of cytosine methylation on DNA binding specificities of human transcription factors'. Science, 5 May 2017.


News Article | February 23, 2017
Site: www.materialstoday.com

Self-assembly is one of the fundamental principles of nature, directing the growth of larger ordered and functional systems from smaller building blocks. Self-assembly can be observed at all length scales, from molecules to galaxies. Now researchers at the Nanoscience Centre of the University of Jyväskylä and the HYBER Centre of Excellence of Aalto University, both in Finland, report a new type of self-assembly, in which tiny gold nanoclusters just a couple of nanometres in size form two- and three-dimensional materials. Each nanocluster comprises 102 gold atoms and a surface layer of 44 thiol molecules. The study, conducted with funding from the Academy of Finland and the European Research Council, is reported in a paper in Angewandte Chemie International Edition. The atomic structure of the 102-atom gold nanocluster was first resolved by Roger Kornberg’s group at Stanford University in 2007. Since then, further studies of the nanocluster’s properties have been conducted in the Jyväskylä Nanoscience Centre. In this latest study, the Finnish researchers have shown that the nanocluster’s thiol surface possesses a large number of acidic groups able to form directed hydrogen bonds with neighboring nanoclusters, initiating directed self-assembly. This self-assembly took place in a water-methanol mixture and produced two distinctly different superstructures, which were imaged by a high-resolution electron microscope at Aalto University. In one of the structures, two-dimensional, hexagonally-ordered layers of gold nanoclusters were stacked together, each layer being just one nanocluster thick. Under different synthesis conditions, the nanoclusters would instead self-assemble into three-dimensional spherical, hollow capsid structures, where the thickness of the capsid wall corresponds again to just one nanocluster. While the details of the formation mechanisms for the superstructures warrant further investigation, these initial observations suggest a new route to synthetically-made, self-assembling nanomaterials. “Today, we know of several tens of different types of atomistically-precise gold nanoclusters, and I believe they can exhibit a wide variety of self-assembling growth patterns that could produce a range of new meta-materials,” said Hannu Häkkinen, who coordinated the research at the Nanoscience Centre. “In biology, typical examples of self-assembling functional systems are viruses and vesicles. Biological self-assembled structures can also be de-assembled by gentle changes in the surrounding biochemical conditions. It’ll be of great interest to see whether these gold-based materials can be de-assembled and then re-assembled to different structures by changing something in the chemistry of the surrounding solvent.” “The free-standing two-dimensional nanosheets will bring opportunities towards new-generation functional materials, and the hollow capsids will pave the way for highly lightweight colloidal framework materials,” predicted postdoctoral researcher Nonappa from Aalto University. “In a broader framework, it has remained as a grand challenge to master the self-assemblies through all length scales to tune the functional properties of materials in a rational way,” said Olli Ikkala from Aalto University. “So far, it has been commonly considered sufficient to achieve sufficiently narrow size distributions of the constituent nanoscale structural units to achieve well-defined structures. The present findings suggest a paradigm change to pursue strictly defined nanoscale units for self-assemblies.” This story is adapted from material from the Academy of Finland, with editorial changes made by Materials Today. The views expressed in this article do not necessarily represent those of Elsevier. Link to original source.


News Article | February 28, 2017
Site: globenewswire.com

Formulae used in calculating key figures Equity ratio = Equity / balance sheet total Earnings per share = Profit for period / average number of shares Average number of shares = Weighted average number of shares. The number of shares is weighted by the number of days each share has been outstanding during the review period. Guidance for 2017 The company does not expect essential revenues in 2017. The company continues to invest in its ongoing development programs in Secondary Lymphedema and Parkinson's disease, and expects to be cash positive at the end of the year. Outlook for 2017 Herantis' long-term goal is to significantly increase its business through commercialization agreements for its drug candidates. The company continues discussing collaboration possibilities with potential development partners for its development programs. Thanks to the significant grant awarded by the European Union's the company can continue its drug development further than previously estimated before signing any collaboration agreements to optimize shareholder value in Herantis. The main objectives for 2017 are recruiting and safely treating patients in the clinical trials with Lymfactin® and CDNF. Both of these drug candidates aim at a breakthrough in unmet clinical needs and are based on leading science in their fields. Pekka Simula, CEO: The hard work of our team was rewarded in 2016 with two internationally significant achievements. We were the first in the world to treat patients with a gene therapy intended for repairing damages of the lymphatic system. We were awarded a highly competitive EU grant for a clinical study aiming at a breakthrough in the treatment of Parkinson's disease. These milestones are even more remarkable as they are independent of each other and they are both based on leading scientific research in their fields. Some people have asked me why develop a drug for the treatment of Parkinson's disease since such drugs already exit and sell for billions of euro annually. I answer: Please join me to the next Parkinson's patient association meeting, when they again invite us to share our development updates. Yes, the currently available drugs help patients live with their disease - for a while. I don't think any patient considers those drugs sufficient. The telegraph was a revolutionary invention at its time. So why did we need telephones? Or mobile phones? The development of biological drugs aims at the same order of magnitude in medical breakthroughs. We want to modify the disease instead of just alleviating its symptoms like many current drugs do. And we want to function via several biologically relevant mechanisms. Professor Mart Saarma and his research group have for years continued their tireless scientific research thanks to which our drug candidate CDNF offers a new promise to patients with Parkinson's disease. It is even easier to understand the importance of drug development for the treatment of lymphedema: There are no approved therapeutics. Many patients don't even know that this disease, which severely affects their quality-of-life has a name. Too many are ashamed of their symptoms and suffer in silence. Fortunately there are brave women like Hollywood-actress Kathy Bates thanks to whom lymphedema awareness has significantly increased and patients have started to demand new treatments more actively. Herantis' Lymfactin® is a gene therapy aiming at curing lymphedema by repairing damages of the lymphatic system. Based on the leading research by professor Kari Alitalo, Lymfactin® is the first clinical stage gene therapy in the world designed to repair the lymphatic system. CDNF and Lymfactin® are both modern, biological drug candidates. The challenges in their development are much greater than of conventional small molecule drugs. The biological drug substances are clearly more complicated by nature; their regulatory requirements and guidelines tend to have much more room for interpretation and demand scientific background work. Development of this kind of drug candidates is practically continuous problem solving. On the other hand they typically hold a much bigger promise than small molecule drugs. For instance CDNF impacts simultaneously several mechanisms of Parkinson's disease. In addition, small molecule drugs are usually foreign compounds to our bodies, which can lead to adverse effects. Herantis' CDNF is a protein, which is naturally present in the human brains and blood. Also the active substance of Lymfactin®, VEGF-C, is such an endogenous protein. Our drug candidates aim at leveraging the natural repair mechanisms of the human body based on the latest scientific data. 2016 was a very successful year for us as our hard work and high-class science lead to the first patient treatments with Lymfactin® and a significant, highly competitive EU grant for patient treatments with CDNF. Either achievement alone is a significant, internationally renowned recognition of the academic research of Finland, a nation celebrating 100 years of independency this year. These achievements are also exactly what we are aiming at: Translating top science to clinical work so this leading science could eventually help patients everywhere in the world. Herantis' public release practice has sometimes been criticized as sparse. My humble opinion is that some drug development companies appear too anxious or greedy as their public disclosures generate excess hype in this field of high development risks. Herantis discloses achievements that actually matter, such as those mentioned above. There are even hundreds of scientific experiments and dozens of applications behind a single clinical study authorization. Would it be reasonable investor relations to disclose each of them? Would it be honest publicity to selectively report the most promising? Despite our Spartan release practice we are an open, approachable and patient centric drug developer who takes pride in responding to each patient enquiry. The patient viewpoint was considered for instance in my blogging last September. 2016 was a tough year at Herantis full of hard work; eventually it was also a very rewarding year for the entire team. Our warm thanks especially to all you patients who have contacted us and whose support motivates us from day to day. REVIEW OF OPERATIONS JANUARY 1-DECEMBER 31, 2016 Herantis' drug development Herantis develops innovative drug based on leading scientific research in their fields and aiming at breakthrough in unmet clinical needs. The company's objective is to establish the safety of its drug candidates in early-stage clinical studies, show signals of their efficacy, and then close commercialization agreements with larger pharmaceutical companies. In 2016 the drug development of Herantis proceeded favorably with the first clinical study with Lymfactin® launched and the first clinical study with CDNF awarded a significant EU grant. Lymfactin® for breast cancer associated lymphedema Breast cancer treatments can cause damage to lymph nodes, which may lead into secondary lymphedema. The common symptoms of secondary lymphedema are persistent swelling of the affected limb, thickening and hardening of skin, limited limb mobility, pain, and increased sensitivity to inflammations. Secondary lymphedema is a chronic, progressive disease that severely decreases the patient's quality of life. Current treatments such as compression garments, special massage, and exercise may relieve symptoms but do not cure the condition, which is caused by damage to the lymphatic system. Herantis' Lymfactin® is a gene therapy drug that produces a growth factor called VEGF-C, which is highly selective to the growth of lymphatic vessels. Based on preclinical results Lymfactin® is expected to promote the regeneration of lymphatic vessels and thus repair damages of the lymphatic system. Lymfactin® is based on research at an Academy of Finland Centre of Excellence led by Professor Kari Alitalo at the University of Helsinki. In 2016 Herantis started a Phase 1 clinical study with Lymfactin®. The primary objective of the study is to evaluate the safety and tolerability of Lymfactin®. Signals of efficacy of Lymfactin® will also be assessed. The study is conducted at three university hospitals in Finland aiming to complete patient recruitment in 2017. CDNF neuroprotective and neurotrophic factor for Parkinson's disease Herantis develops its drug candidate CDNF for the treatment of Parkinson's disease. Parkinson's disease is a slowly progressing neurodegenerative disease that cannot be cured. Estimated 7 million people worldwide have Parkinson's disease. Known treatments only alleviate the motor symptoms of the disease but have no effect on its progress. In addition, the effect of the treatments may be reduced over time. Herantis aims at significant improvement to current treatments. CDNF, a naturally present protein in humans that was discovered in long-term academic research led by Professor Mart Saarma, has in preclinical studies alleviated both motor and non-motor symptoms of Parkinson's disease and also slowed down its progress. Herantis has completed the toxicology studies on CDNF required by the regulatory authorities. Owing to the promising scientific results and strong development work the European Union awarded a grant of approximately €6 million for the Phase 1-2 clinical study with CDNF in Parkinson's disease. The grant period starts formally Jan 1st, 2017 and patient recruitment is intended to begin in the first half of 2017. The objectives of the clinical study are evaluating safety and signals of efficacy in 18 patients with Parkinson's disease at three university hospitals in Finland and Sweden. CDNF neuroprotective and neurotrophic factor for ALS ALS (Amyotrophic Lateral Sclerosis) is a fatal motor neuron disease. As the disease progresses the patient loses control of her muscles, which leads to difficulties in motion, speech, swallowing, and breathing. The estimated average survival from symptom onset is from two to five years. There is no known cure; present treatments can only alleviate the symptoms of ALS. An estimated 140,000 people contract ALS annually. The European Medicines Agency EMA and the US Food and Drug Administration FDA both granted Orphan Designation for Herantis' CDNF for the treatment of ALS in 2016 based on the preliminary preclinical results on its possible efficacy. The company is exploring possibilities to start a clinical development program in ALS. Decisions on starting such a program have not been made and no funding is allocated. Dry eye syndrome (Keratoconjunctivitis sicca) is the most common cause of irritation in the eye. Its typical symptoms include dryness of the eye, a burning sensation, pain, redness and the sensation of a foreign body in the eye. Severe or prolonged dry eye syndrome may damage the surface of the eye and reduce eyesight. Herantis' Phase 2 randomized clinical study of the cis-UCA eye drop for the treatment of dry eye was completed in 2015. The study did not show statistically significant improvements in the primary endpoints in comparison with placebo. Herantis will however continue partnership negotiations in 2017 for product development collaboration. FINANCIAL REVIEW JANUARY 1-DECEMBER 31, 2016 Income from business operations, R&D expenses Herantis Group did not have essential revenues in 2016 or in the corresponding period in the previous year. The R&D expenses for the review period were €1.8 million, recorded in the profit and loss statement as an expense for the period. The R&D expenses for the review period mainly comprised for the preparation expenses for the clinical trials of CDNF for the treatment of Parkinson's disease and Lymfactin® for the treatment of breast cancer associated lymphedema. The Group's R&D expenses for the corresponding period in the previous year, €4.9 million, were recorded as the review period's expenses in the profit and loss statement. The profit for the review period was €-4.4 million. The consolidated profit for the comparison period was €-16.0 million. Financing and capital expenditure The company's cash and cash equivalents on December 31, 2016 amounted to €2.8 (at the end of the previous reporting period on December 31, 2015: €5.5) million. In addition the company has R&D loans previously granted by the Finnish Funding Agency for Innovation, Tekes, to be drawn in the amount of €1.9 million. During the review period Herantis draw about €0.4 (1.2) million in Tekes loans. In addition the European Union has awarded a grant of about €6.0 million for the project TreatER. The TreatER project is essentially the Phase 1-2 clinical study of Herantis with CDNF for the treatment of Parkinson's disease. The consolidated cash flow from operations in the review period was €-3.0 (€-7.4) million. Acquisitions and directed share issues Herantis reported on January 14, 2016 that in accordance with the authorization by the company's annual meeting of shareholders 2015, the Board of Directors decided on December 1, 2015 on a directed share issue to Broadview Ventures I, LLC according to a subscription agreement between the parties. Broadview Ventures I, LLC fully subscribed to this share issue, a total of 32,311 new shares for a subscription price of €10.00 per share. As a result of the share issue, the total number of shares of the company increased to 4,118,305 shares on January 12, 2016. The share capital did not increase with subscriptions. The entire subscription price of EUR 323,110.00 was entered in the invested unrestricted equity reserve of the company. As a result of the share subscriptions, the number of shares of Herantis Pharma Plc increased to 4,118,305 shares. The new shares were subject to trading on the Nasdaq Helsinki Ltd's First North marketplace together with the old shares as of 14 January 2016. In 2016, Herantis redeemed the entire share capital of its subsidiary Laurantis Pharma Ltd. Previously Herantis had held approximately 99% of the shares in Laurantis Pharma Ltd. Balance sheet The consolidated balance sheet on December 31, 2016 stood at €10.2 million. At the end of the previous review period on December 31, 2015 the consolidated balance sheet stood at €14.1 million. At the end of the review period on December 31, 2016, the consolidated balance sheet included short-term debt in the amount of €0.7 (0.6) million, long-term loans in the amount of €7.9 (7.4) million, and capital loans in the amount of €0.1 (0.1) million. Financing earnings and expenses totaled €0.0 (0.1) million. No R&D expenses were capitalized during the review period. Equity Consolidated equity on December 31, 2016 was €1.6 million. At the end of the previous review period on December 31, 2015, consolidated equity amounted to €6.0 million. The change is a result of the consolidated loss of the review period. Personnel, management, and administration The number of personnel at the end of the review period on December 31, 2016 was 7 persons (at the end of the previous reporting period on December 31, 2015: 7). During the review period, the company's Board of Directors comprised Pekka Mattila (Chairman), Jim Phillips, Aki Prihti, Timo Veromaa and Frans Wuite, The Managing Director for the company was Pekka Simula. Ordinary Annual General Meeting 2016 Herantis' ordinary Annual General Meeting (AGM) was held on April 11, 2016. The AGM adopted the annual accounts for financial year 2015 and resolved to discharge the members of the Board of Directors and the Managing Director from liability. In accordance with the proposal by the Board of Directors, the AGM resolved that no dividend be paid for the financial period January 1-December 31, 2015, and that the loss for the period be recorded on the profit and loss account. The AGM resolved that the remuneration for the members of the Board of Directors shall be €1,000 per month, with the exception of its Chairman, whose remuneration shall be €2,000 per month. It was further resolved that the Board members shall be eligible to subscribe to stock options of option program 2014 I, according to the rules of which the Board members can be granted stock options for each full 12-month period as a Board member. The AGM decided that the Auditor will be paid reasonable remuneration in accordance with its invoice approved by the company. The firm of authorized public accountants PricewaterhouseCoopers Oy was appointed Herantis Pharma Plc's Auditor for the term ending at the closing of the next Annual General Meeting of shareholders, with Mr. Martin Grandell, APA, as the responsible auditor. Share based incentive program Herantis has five stock option programs: Stock option program 2010, Stock option program 2014 I, Stock option program 2014 II, Stock option program 2014 III, and Stock option program 2016 I, whereby stock options have been offered to senior employees of the company to increase their commitment toward long-term contribution to growing shareholder value. The essential details of the stock option programs are listed in the table below. More detailed information is provided on the company's web site at www.herantis.com . 1 The maximum number of shares to be subscribed by stock options. However the share subscription periods of Stock option programs 2014 II and 2014 III have expired by 31 Dec 2016 and their subscriptions will no longer be accepted. Risks and uncertainties Herantis is a drug development company and the general risks and uncertainties present in drug development also apply to its operations. Further, Herantis develops novel biological drugs based on novel scientific research and with mechanisms different from currently approved drugs. Therefore the risks and uncertainties can be considered larger than in conventional drug development. The significant risks and uncertainties in Herantis' business operations are detailed in the IPO prospectus dated May 12, 2014 that is available on the company's website at www.herantis.com. The medical risk related to the cis-UCA eye drop is partly realizing as the efficacy of the drug candidate proved weaker in the Phase 2 clinical studies than expected on the basis of preclinical studies. Shares and shareholders The market capitalization of Herantis Pharma Plc at the end of the review period on December 31, 2016 was €11.7 million. The closing price of the company's share on December 31, 2016 was €2.85. The highest share price during the review period was €4.50, lowest €0.77, and average €1.25. According to Herantis' shareholder register dated on December 31, 2016, the company had 633 registered shareholders. The members of Herantis' Board of Directors and the CEO held in aggregate 53,366 (Dec 31, 2015: 39,761) shares including shares held through their controlled companies, or 1.3 (0.9) percent of the company's total stock. Information on insider trading with the company's shares is published on the company's website. Events after the review period No essential updates have taken place after the review period. The Board's proposal for the use of distributable funds The parent company of Herantis Pharma group is Herantis Pharma Plc whose distributable equity was €6.9 million according to balance sheet 31 December 2016. Herantis Pharma Plc had no essential revenue in 2016. The financial result of the parent company for 2016 was €-2.7 million. The Board of Directors proposes to the Annual General Meeting convening on April 11, 2017 that no dividend be paid for the financial period January 1-December 31, 2016. Accounting policies These financial statements have been prepared according to good accounting practice, local legislation and the rules of the First North market. The figures in the financial statements are audited. The figures are individually rounded from exact figures. Financial information 2017 This financial statements release and its appendices is published in Finnish and in English on February 28, 2017 on the company's website at www.herantis.com. In case of any discrepancies between the language versions, the Finnish version shall prevail. The company's annual report will be released on the company's website latest by March 17, 2017. A half-year interim report for January-June 2017 will be published on Tuesday, August 29, 2017. The ordinary Annual General Meeting of shareholders is scheduled for Tuesday, April 11, 2017. APPENDICES Profit and loss statement and Balance sheet January 1-December 31, 2016 Statement of cash flow January 1-December 31, 2016 Statement of changes in equity Herantis Pharma in brief: Herantis Pharma Plc is an innovative drug development company focused on regenerative medicine and unmet clinical needs. Our first-in-class assets are based on globally leading scientific research in their fields: CDNF for disease modification in neurodegenerative diseases, primarily Parkinson's and ALS; and Lymfactin® for breast cancer associated lymphedema, with potential also in primary lymphedema. The shares of Herantis are listed on the First North Finland marketplace run by Nasdaq Helsinki Ltd.


The purpose of this systematic review was to study the relative health risks of poor cardio-respiratory fitness (or physical inactivity) in normal-weight people vs. obesity in individuals with good cardio-respiratory fitness (or high physical activity). The core inclusion criteria were: publication year 1990 or later; adult participants; design prospective follow-up, case-control or cross-sectional; data on cardio-respiratory fitness and/or physical activity; data on BMI (body mass index), waist circumference or body composition; outcome data on all-cause mortality, cardiovascular disease mortality, cardiovascular disease incidence, type 2 diabetes or cardiovascular and type 2 diabetes risk factors. Thirty-six publications filled the criteria for inclusion. The data indicate that the risk for all-cause and cardiovascular mortality was lower in individuals with high BMI and good aerobic fitness, compared with individuals with normal BMI and poor fitness. In contrast, having high BMI even with high physical activity was a greater risk for the incidence of type 2 diabetes and the prevalence of cardiovascular and diabetes risk factors, compared with normal BMI with low physical activity. The conclusions of the present review may not be applicable to individuals with BMI > 35. © 2009 International Association for the Study of Obesity.

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