On 9 May 1950 the Frenchman Robert Schuman, then minister for foreign affairs, presented a declaration proposing the coalition of European countries for economic benefit in peaceful trade. By pooling Europe’s coal and steel resources, Schuman’s declaration is considered as the first step towards what is now the European Union. Proposed fewer than five years after the end of World War II, in which more violations of human rights were committed than any conflict before or since, the Schuman Declaration brought about the European Coal and Steel Community (ECSC) which sought to broker the agreed pooling of resources and thereby rendering another such war ‘not merely unthinkable, but materially impossible’. ‘The setting up of this powerful productive unit,’ the declaration continues, ‘open to all countries willing to take part and bound ultimately to provide all the member countries with the basic elements of industrial production on the same terms, will lay a true foundation for their economic unification.’ The declaration was accepted and founded by the governments of the original member nations (France, west Germany, Italy, Belgium, the Netherlands and Luxembourg) who foresaw that the combining of international economic interests would also increase quality of life for employees in the coal and steel industries, and so other nations were invited to join in the name of continuing and expanding co-operation and peace. ‘World peace,’ Shuman’s declaration begins, ‘cannot be safeguarded without the making of creative efforts proportionate to the dangers which threaten it. ‘The contribution which an organised and living Europe can bring to civilisation is indispensable to the maintenance of peaceful relations.’ Today, Europe celebrates its enduring commitment to unification and prosperity with events organised across the bloc. Commissioner for Science, Research and Innovation Carlos Moedas will, for example, be in attendance at the National Museum of Science in Lisbon, in his home country of Portugal, where he aims to introduce the Investment Plan for Europe and the work of the EU’s research and innovation framework programme, Horizon 2020, to a wider than usual audience. The post Europe Day celebrations underway appeared first on Horizon 2020 Projects.

A blood test has been developed by a Swedish SME to augment the detection of new cases of pancreatic cancer. Funded by the European Commission’s Horizon 2020 framework programme, clinical validation has begun with the aim of making the diagnostic available as soon as possible. The Immpact project focuses on the final stages of the development of the new blood test and was launched in June 2015 for a duration of two years. Implemented by Swedish start-up Immunovia, the principle behind the innovation is identifying the blood residue pancreatic cancer leaves. These trace residues exist prior to the more distinctive symptoms. All that remains is to detect them earlier. Immunova CEO Mats Grahn said: “The objective is to carry out the studies and commercialisation activities that are needed to take our invention from a prototype to a test that is available to the public. There is no solution whatsoever on the market at the moment.” Because of this scarcity of solutions, the Immpact project was recognised by the EU, and by Horizon 2020, as a worthy innovation to fund. This backing has enabled Immunovia to take the next steps towards commercial availability, with their current aim of completing the project in June next year. Known as IMMrayTM PanCan-d, the blood test is being vindicated through various clinical studies, wherein 1,400 samples taken from pancreatic cancer sufferers, as well as healthy control subjects, are already available. Early findings show IMMrayTM PanCan-d can detect pancreatic cancer in far earlier stages with an accuracy of 96%. Horizon 2020 has funded this project with costs in excess of €4m. The post H2020 pancreatic cancer detection project appeared first on Horizon 2020 Projects.

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Fig. 1 Researchers at the Laboratory of Molecular Virology and Biological Chemistry of the IMB PAS, from left to right; Dr Krzysztof Zwoliński (transferred), Patrycja Suski (transferred), Professor Agnieszka Olejniczak, Professor Zbigniew Leśnikowski (head of the laboratory), Dr Mirosława Studzińska, Agnieszka Jabłońska, Professor Edyta Paradowska, Anna Adamska (transferred), Sławomir Janczak, Magdalena Białek-Pietras. Aleksandra Rembowska (not shown) and Konrad Głąbała (not shown) The Laboratory of Molecular Virology and Biological Chemistry of the Institute of Medical Biology at the Polish Academy of Sciences works towards understanding the genetic basis of Cytomegalovirus (CMV) pathogenesis and chemotherapy of the virus infections. Viruses are small infective agents that cannot reproduce themselves without a host cell, they replicate only inside the living cells of other organisms. Viruses can infect all types of life forms and are therefore present everywhere, on or in just about every material and environment on Earth from soil to water and air. Some viruses enter a host and leave virtually unnoticed, others cause disease and destroy the host. Some viruses do not cause disease in a healthy host but constitute a danger for individuals with a compromised immune system. Others can leave their genetic material in the host cell where it remains dormant for an extended time (latent infection). When the cell is disturbed, the virus may begin replicating again and cause disease. Viruses still evolve through different mechanisms. Therefore, new, mutated strains and new viruses are constantly emerging, presenting a continuous challenge in attempts to control the diseases they cause. Cytomegalovirus – an opportunistic pathogen In the Laboratory of Molecular Virology & Biological Chemistry we are interested in nucleic acids, both in their chemistry and molecular biology, especially in viral DNA/RNA. We focus on viruses belonging to the Herpesviridae family, with special attention on human cytomegalovirus (CMV). CMV is a widely spread beta-herpesvirus that infects 40-100% of the adult population worldwide. CMV infection promotes allograft rejection and graft-versus-host disease in solid organ and bone marrow transplant recipients. It is also an important pathogen in other immunocompromised patients, including oncological patients undergoing radio or chemotherapy, and AIDS patients with low CD4+ counts. Other kinds of problems prevail in prenatal and perinatal cases of CMV disease. CMV is the most common cause of viral intrauterine infection. In pregnant, immunocompetent women infections with CMV are usually asymptomatic or resembling mononucleosis, and often give rise to undetected latent infections and re-infections. However, severe infections may occur among congenitally infected foetuses and infants due to immaturity of the immune response. There is also increasing evidence that persistent CMV infection may contribute to the pathogenesis of such diseases as diabetes Type 1, atherosclerosis, coronary artery disease, hypertension or immunosenescence. A better understanding of CMV’s molecular biology is hoped to spawn novel strategies for prevention, diagnosis and treatment of CMV-related illness. The areas of research ongoing in our laboratory include: 1) CMV genetic variability and its effect on virus pathogenicity; 2) innate immunity; 3) the role of pattern recognition receptors (PRRs) and cytokines in congenital CMV infections, and 4) the relevance of selected Toll-like receptors (TLRs) polymorphism to symptomatic herpesvirus infection (CMV, EBV). Our research interests also concern viral mechanisms for immune evasion and interaction with the host immune system. We found that some CMV genotypes are associated with clinical manifestations in children with congenital or postnatal infections. Detection of the specific gN, gH and vCXCL-1 genotype may be indicative of serious manifestations of CMV infection in infants. We observed also that some TLR9 polymorphisms could be a genetic risk factor for the development of CMV disease. There is no available vaccine for preventing CMV at present. A few CMV vaccines are being tested in humans, including live attenuated virus vaccines and vaccines that contain only pieces of the virus. However, prospects of CMV vaccine development are uncertain. Thus, chemotherapy of CMV infections is important in the cases where control of the virus is necessary. Therefore, another area of the Laboratory of Molecular Virology and Biological Chemistry’s activities is the search for new therapeutic agents, with attention to compounds with anti-CMV activity. Anti-CMV chemotherapy The current anti-CMV treatments, in addition to foscarnet which has been known for many years, include ganciclovir and its pro-drug, valganciclovir. Ganciclovir is a first-line drug and drug of choice. In the treatment of CMV pneumonia, CMV-specific immunoglobulin is administered, usually in combination with ganciclovir. The second-line medications include foscarnet and cidofovir. The major clinical indication for foscarnet or cidofovir is the treatment of CMV retinitis in HIV-infected patients and treatment of immunocompromised patients with CMV disease resistant or unresponsive to ganciclovir. A high-dose of the anti-herpes simplex virus (HSV) drug aciclovir has also been used as a prophylactic against CMV with some successes, but it is not recommended clinically for CMV treatment. Fomivirsen, an antisense oligonucleotide, was approved for CMV retinitis treatment as an intravitreal injection in 1996, but was later withdrawn from the market. While with currently available systemic anti-CMV drugs the virus load can often be successfully controlled, their use is hampered by limited efficacy, side effects and development of resistance. All these create a need for a new generation of more efficient and safer drugs against this opportunistic and widely spread pathogen. Medical prospects of drugs with boron clusters Boron-containing nucleosides were originally designed as prospective boron carriers for boron neutron capture therapy (BNCT) of tumours. As boron-rich donors in boron-carrying molecules dicarba-closo-dodecaboranes (C2B10H12) are frequently used due to their chemical and biological stability and physicochemical versatility. Other biological applications of boron cluster-nucleoside conjugates include modulation of purinergic receptor activity, inhibition of blood platelets aggregation, inhibition of reactive oxygen species production, antiviral or anticancer activity, and DNA/RNA-oligonucleotide modification. The fact that polyhedral boron hydrides are man-made molecules and are unfamiliar to life has potential advantages. This is because the active substances bearing boron cluster modifications are less likely to be prone to the development of resistance and are expected to be more stable in biological systems compared to carbon-based molecules. While pathogens, such as bacteria and viruses, are eventually capable of evolving resistance against almost any molecule that attacks them, one could hypothesise that this process would take longer for boron-based compounds. Technically, two major avenues in the search for new biologically active molecules containing boron clusters are exploited. The first is based on the modification of natural products, previously identified molecular tools or clinically used drugs with the hope for finding compounds with improved biological or pharmacokinetic properties. The second approach focuses on the screening of available collections of compounds in search of novel structures with desired activities and properties. We use both approaches obtaining, among others, a series of boron cluster modified, clinically used antiviral drugs such as aciclovir (ACV), cidofovir (CDV), ganciclovir (GCV), valganciclovir  (VGCV) and Tamiflu®, as well as libraries of novel compounds, derivatives of pyrimidine and purine nucleosides, modified within the nucleobase or sugar residue with different types of boron clusters. One of the most potent new compounds identified was 5-[(1,12-dicarba-closo-dodecaboran-2-yl)ethyn-1-yl]-2’-deoxyuridine with IC50 value 5.5μM and selectivity index higher than 180. It is unusual that it exhibited high antiviral activity against CMV and was not active against HSV-1, another virus belonging to the Herpesviridae family. The antiviral activity of pro-drugs of ACV, CDV, GCV and VGCV was lower or similar to that of the original drug. It should be noted, however, that due to the presence of centres of chirality in the carbon atoms, the studied pro-drugs were used in antiviral assays as a mixture of enantiomers (GCV, ACV) or diastereomers (CDV) without separation into individual species. One can presume that the activity of one or the other stereoisomer alone was higher. These works, and the works of others, allow for moderate optimism that the medicinal chemistry of boron clusters may soon become a productive area of drug discovery providing innovative bioactive molecules, including anti-CMV agents. Professor Zbigniew J Leśnikowski Molecular Virology & Biological Chemistry Lab, Polish Academy of Sciences +48 422723629 zlesnikowski@cbm.pan.pl http://www.cbm.pan.pl The post Life with CMV appeared first on Horizon 2020 Projects.