Researchers develop mammalian cell cycle model

The cell division process plays an important role for single-cell and multi-cell organisms, especially for transforming fertilised eggs into mature organisms. Failure to control the cell cycle can result in tumour proliferation and cancer …

EU findings open door to better drugs for fight against heart attacks and strokes

Researchers partially funded by the EU have made discoveries that could open the door to the development of new and better-targeted drugs for patients at risk of strokes or heart attacks. Writing this week in the journal Cell, the results are the …

Scientists shed light on mystery behind myelin membrane synthesis

A set of protein processes needed in the early-stage conversion of glucose into fatty acids plays a central role in the proper formation and layering of myelin membrane, new research shows. The findings are part of the EU-funded AXON SUPPORT and NEUROMICS projects, which received EUR 1.3 million and EUR 1 million in support, respectively. The results, presented in the journal Proceedings of the National Academy of Sciences (PNAS), show how the use of X-rays uncovered how mutations affect the structure of myelin, an area of research crucial for neurological disorders. The researchers from Boston College in the US collaborated with colleagues in Italy, Japan, the Netherlands and Switzerland to evaluate how the composition of myelin lipids impacts the myelin structure and stability. The proper functioning of the body's nervous system relies on the myelin sheaths that surround the neurons' axons. 'Myelination requires a massive increase in glial cell membrane synthesis. Here, we demonstrate that the acute phase of myelin lipid synthesis is regulated by sterol regulatory element-binding protein (SREBP) cleavage activation protein (SCAP), an activator of SREBPs,' the authors of the study write. Boston College's Professor Daniel Kirschner said: 'Myelin is a stack of membranes providing insulation to the axon, and with that insulation comes rapid nerve conduction. If myelin becomes defective, the membranous insulator becomes leaky and the nerve doesn't conduct as well. If myelin is totally missing along part of an axon, the nerve conduction is blocked.' The team used X-ray diffraction to get a look at the dynamic membrane assembly in complete nerve samples obtained from mice engineered to mimic myelinic diseases. According to Professor Kirschner, when comparing X-ray diffraction with other microscopy techniques, the team found that the former provides fast, clean and clear results on the intermodal myelin's structural integrity. 'We were able to tell that the packing of the membranes was abnormal, which could affect the electrophysical properties of myelin,' the Boston College biologist said. 'We also saw that the packing of the lipids in the myelin lipid bilayers was more disordered in samples from the transgenic mice used here.' The researcher went on to say that other types of microscopy introduce chemical modifications to the tissue being evaluated. The molecular structure can be altered by these agents and by the time used to prepare and analyse the samples, which can also mask the dynamic interactions of myelin. 'X-ray diffraction requires no chemical treatments and can be completed in about an hour,' he said. 'The advantages of X-ray diffraction are that we can examine and analyse whole pieces of tissue and give information about the effect of the mutation on the native structure of the myelin as well as on its stability.' The research team has been using genetically altered mice for around four years as part of research into the role of myelin degeneration in various diseases of the central and peripheral nervous systems. AXON SUPPORT ('Axonuclear communication in health and disease') was funded under the 'New and emerging science and technology' (NEST) Thematic area of the EU's Sixth Framework Programme (FP6). NEUROMICS ('Functional genomics of the brain') was supported by the FP6's Marie Curie Actions - Early Stage Training.
Quality validation date: 2009-12-14

EU-funded researchers gain insights into genetics of lung functioning

A large-scale study has identified five new genetic loci (points on the genome) associated with the health of the human lung and pulmonary function. Publishing in the latest edition of the journal Nature Genetics, the partly EU-funded researchers explain that their findings shed new light on the molecular basis of lung disease and might lead to better treatment of chronic obstructive pulmonary disease (COPD), asthma and similar conditions. The researchers studied samples from more than 20,000 people, mapping specific loci linked to two clinically relevant measures of lung function. Those measures are forced expiratory volume in the first second (FEV1), which represents the amount of air that can be exhaled in the first second, and the ratio of FEV1 to forced vital capacity (FVC). FVC stands for the amount of air that can be exhaled after full inspiration. From a clinical point of view, both measures are important indicators of population morbidity and mortality and form the diagnostic basis for COPD. It is also a well-known fact that pulmonary function is in part determined by genetic factors. The research, conducted by 96 scientists in Europe and Australia and led by Dr Martin Tobin of the University of Leicester, UK, and the University of Nottingham's Professor Ian Hall, pinpointed five genetic loci that play a role in the functioning of the lungs. These loci were observed in the whole population and were not specific to smokers, for instance. In addition, three of the loci were also identified in a second study, published in the same edition of Nature Genetics. The work of the CHARGE ('Cohorts for Heart and Aging Research in Genomic Epidemiology') consortium is based on a different, but equally large set of samples and thus corroborates some of the findings of Dr Tobin and his colleagues. 'This work is important because until now we have known very little about the genetic factors that determine an individual's lung function,' the researchers say. 'By identifying the genes important in determining lung function, we can start to unravel the underlying mechanisms which control both lung development and lung damage. This will lead to a better understanding of diseases such as ... COPD and asthma. Crucially, it could open up new opportunities to manage and treat patients with lung conditions.' The scientists add: 'A large reduction in lung function occurs in ... COPD, which affects around 1 in 10 adults above the age of 40 and is thought to be the 4th most common cause of death worldwide. Smoking is the major risk factor for development of COPD. Lung function and COPD cluster within families, indicating that variations in genes also predispose individuals to reduced lung function.' Both studies were partly funded by the EU through the following projects: EURO BLCS ('Biological, clinical and genetic markers of future risk of cardiovascular disease') and GENOMEUTWIN ('Genome-wide analyses of European twin and population cohorts to identify genes in common diseases'), both funded under the Fifth Framework Programme (FP5); GABRIEL ('A multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community') and EUROSPAN ('European special populations research network: quantifying and harnessing genetic variation for gene discovery'), both supported through the Sixth Framework Programme (FP6); and GEFOS ('Genetic factors for osteoporosis'), a project that is part of the Seventh Framework Programme (FP7).
Quality validation date: 2009-12-14

Researchers develop mammalian cell cycle model

The cell division process plays an important role for single-cell and multi-cell organisms, especially for transforming fertilised eggs into mature organisms. Failure to control the cell cycle can result in tumour proliferation and cancer development. Researchers from Université Libre de Bruxelles (ULB) in Belgium have developed a detailed dynamics model of the mammalian cell cycle. The findings, published in the Proceedings of the National Academy of Sciences (PNAS) journal, will help raise awareness of the cell cycle's role in the pathology and normal functioning of living organisms. The research is part of the EU-funded BIOSIM ('Biosimulation - a new tool in drug development') project, which received almost EUR 11 million under the 'Life sciences, genomics and biotechnology for health' Thematic area of the EU's Sixth Framework Programme (FP6). BIOSIM is coordinated by the Technical University of Denmark, and includes partners from Belgium, Germany, Spain, France, Hungary, the Netherlands, Slovakia, Sweden and the UK. According to the researchers, data obtained over the last 20 years have indicated that the cell cycle is controlled by a cyclin-dependent kinases (Cdks) protein network. 'Progression in the cell cycle is controlled by the sequential, transient activation of a family of Cdks, which allow an ordered succession of the cell cycle phases, even though there appears to be a certain overlapping of the different cyclins and Cdks,' the authors of the study wrote. 'The Cdk proteins are active only when forming a complex with their corresponding cyclin.' The ULB researchers, however, determined that because of the complexity of the regulation process of the Cdk network and the difficulty in predicting its evolution, computer simulations of ideal behaviour models would provide the answers scientists have been looking for. ULB PhD student Claude Gérard developed the very detailed model signifying the dynamics of the mammalian cell cycle. 'The model contains four Cdk modules regulated by reversible phosphorylation, Cdk inhibitors, and protein synthesis or degradation,' the research showed. 'Growth factors (GFs) trigger the transition from a quiescent, stable steady state to self-sustained oscillations in the Cdk network. These oscillations correspond to the repetitive, transient activation of cyclin D/Cdk4-6 in G1, cyclin E/Cdk2 at the G1/S transition, cyclin A/Cdk2 in S and at the S/G2 transition, and cyclin B/Cdk1 at the G2/M transition.' The team highlighted how the model predicts that in the presence of suprathreshold amounts of growth factor the regulatory interactions within the Cdk network can suddenly generate sustained oscillations that correspond to the controlled and repetitive activation of the different cyclin/Cdk complexes along the cell cycle process. 'The present results suggest that the sequential activation of the Cdk modules in the Cdk network is brought about by temporal self-organisation corresponding to the global, periodic operation of the mammalian cell cycle,' the authors noted.
Quality validation date: 2009-12-11

EU findings open door to better drugs for fight against heart attacks and strokes

Researchers partially funded by the EU have made discoveries that could open the door to the development of new and better-targeted drugs for patients at risk of strokes or heart attacks. Writing this week in the journal Cell, the results are the first to show the reduction of levels of a specific blood clotting agent involved in the formation of harmful clots within blood vessels without a corresponding increase in the risk of excessive bleeding from surface wounds. The E-RARE ('ERA-Net for research programmes on rare diseases') project contributed to the findings. E-RARE is funded under the 'Coordination of research activities' Thematic area of the EU's Sixth Framework Programme (FP6) to the tune of EUR 2.18 million. The project's main aim is to coordinate existing programmes on rare disease research and to prepare joint and strategic activities linking scattered funding and fragmentation between national research programmes. E-RARE has nine partners from six EU Members States plus Israel and Turkey. The researchers discovered that the molecule polyphosphate can activate a blood clotting agent called 'factor XII' which is involved in the formation of harmful clots within blood vessels. However, factor XII is not involved in surface wound healing. In fact, a lack of the agent is not associated with any hemorrhagic disorder in humans or mice. It is also considered to be redundant for the normal stoppage of bleeding or haemorrhaging. Drugs which reduce the risk of dangerous blood clot formation within blood vessels (thrombosis) lower the risk of heart attacks or strokes. Thrombosis may occur in the venous or arterial circulation causing a heart attack or stroke - the most common causes of death in the developed world. Medication designed to combat thrombosis is called anticoagulant, and have side effects. In mammals, blood clotting involves both cellular and protein components, provided by platelets and coagulation factors. This leaves those taking anticoagulants at risk of severe, or even lethal, bleeding if they injure themselves in any way. 'The challenge in designing treatments to reduce thrombosis is getting the balance right. We need to find an appropriate drug level or target which causes enough anticoagulation to prevent risk of heart attack or stroke but with minimal bleeding side effects,' explained Nicola Mutch from the University of Leeds in the UK. 'Our work suggests polyphosphate or factor XII could be potential new targets,' continued Dr Mutch, 'as neither seems to affect our ability to heal naturally, so drugs based on these molecules could offer a major improvement on existing treatments.'
Quality validation date: 2009-12-11

SANY technology offers easy access to environmental data

Researchers in Europe have worked out a new method to access and reuse environmental data from various sources. The SANY ('Sensors Anywhere') project, which received EUR 7 million under the 'Information society technologies' (IST) Thematic area of the EU's Sixth Framework Programme (FP6), targeted better interoperability of in situ sensors and sensor networks, and faster and cost-efficient reuse of data and services from currently incompatible sources. Easy access and use of environmental data (e.g. on the atmosphere, oceans and land) from sensors found on Earth and in outer space are not readily available. Adding to this challenge is that policy is made from scientific information obtained from these observations. Enter the SANY project that developed the technical means to get this information, easily and freely. 'We are investing lots of resources to make measurements for a particular reason, but the information obtained may never be used again,' explained SANY's coordinator Dr Denis Havlik of the Austrian Institute of Technology (AIT). 'Perhaps people don't know that certain information exists or they cannot access it; sometimes they can access it but they don't know how to use it, or it is too complicated to get in touch with the data owner.' Thanks to the use of a 'service-oriented' architecture, SANY can build applications out of modular services retrieved over the Internet. For example, one service could collect data, while another service could process data. 'The SANY Sensor Service Architecture (SensoSA) allows everybody who makes environmental observations to advertise them over a standardised service interface,' Dr Havlik said. 'Anybody who needs environmental data can go and search for it - or look in a catalogue - and retrieve it using standardised methods.' Regardless of the source of data, its form or how it was retrieved, the SANY system can transform all data to a standard established by the Open Geospatial Consortium (OGC) Ltd, a SANY partner from the UK. Sensor data, whether raw or processed, can be handled by the SANY system, the researchers said. From a market perspective, the SANY proposal can prove lucrative. 'If you are a small company and you believe, for example, that you can predict episodes of air pollution much better than anybody else, then it's easy for you to put your service on the market,' Dr Havlik explained. 'Today, many companies still try to do everything on their own. The new market paradigm envisaged by SANY will allow all involved parties to concentrate on their own strengths, and purchase the missing data and services on an open marketplace.' The results obtained in SANY are significant for two extensive international initiatives: GMES (Global Monitoring for Environment and Security) and INSPIRE. A collaboration between the European Commission and the European Space Agency (ESA), GMES targets long-term interoperability, availability and reliability of earth observation data. INSIPIRE seeks establishment of a 'spatial information infrastructure in Europe'. The SANY partners are from Austria, Belgium, France, Germany, Poland, Spain, Switzerland and the UK.
Quality validation date: 2009-12-10

Europe’s plant communities losing uniqueness, study warns

A combination of extinctions and alien invasions is causing Europe's plant communities to become less unique, according to new EU-funded research published online in the journal Proceedings of the National Academy of Sciences (PNAS). EU support for the study came from the DAISIE ('Delivering alien invasive species inventories for Europe') and ALARM ('Assessing large scale risks for biodiversity with tested methods') projects, both of which are financed under the 'Sustainable development, global change and ecosystems' Thematic area of the Sixth Framework Programme (FP6). One of the commonest ways of assessing biodiversity in a given region or area is to simply count the number of species living there. However, as this latest study reveals, it is also important to work out how closely related the species in a given community are to each other. This is important because a plant community made up of largely unrelated species is more likely to be able to withstand pressures such as changing temperatures or drought. In contrast, in a community of closely related species, if one is unable to withstand high temperatures, for example, chances are that closely related species will also struggle to survive. In this study, the researchers analysed data on the plant species found in different regions of Europe since the year 1500. There are around 11,000 native species of plant in Europe. Since 1500, around 1,600 non-native plant species have arrived in Europe, and 1,700 European species have invaded other European regions to which they are not native. This means that some 53% of plant invasions in Europe can be attributed to species moving from one European region to another. Over the past few centuries, only two European plant species have completely died out. However, around 500 species have become extinct at regional level. For example, the plant blue woodruff (Asperula arvensis) has disappeared from Germany and Austria, largely as a result of the intensification of agriculture, but is still found in Italy and Spain. The fact that invasions vastly outnumber extinctions means that the total number of plant species in European regions has risen. However, the species that have disappeared tend to be relatively rare, and come from plant families that have comparatively few members. In contrast, the invasive species tend to come from species-rich families and are often closely related to species already living in the region. In practice, this means that while the total number of species in the regions studied is rising, the plants within the regions are increasingly similar and the differences between regions are disappearing as the same plants increasingly crop up everywhere. 'Our studies have demonstrated that although the number of species in European regions is rising as the new species outnumber the species that have disappeared, the regions are increasingly losing their phylogenetic and taxonomic uniqueness,' commented Dr Marten Winter of the Helmholtz Centre for Environmental Research (UFZ) in Germany. 'When discussing biological diversity, as well as the pure species number, people should also consider other measures of biological diversity, such as the relationships between the species, for example. These can provide important additional information on the condition and possible risks to the ecosystem.' Researchers participating in the PNAS study come from the Czech Republic, Germany, Greece, Lithuania, New Zealand, Spain, Switzerland and the UK.
Quality validation date: 2009-12-09

XTREEMOS project launches new grid operating system

The use of computational grids, also known as 'grid computing', facilitates people's lives by combining computer resources from various domains for a common task. An EU-funded team of researchers has developed and launched its second Linux-based grid operating system. Under the motto 'Making Grid Computing Easier', the XTREEMOS project has released the second version of its Linux-based Grid operating system. XTREEMOS, which is scheduled to end in May 2010, has received over EUR 14 million in financial support. Funded under the 'Information society technologies' (IST) of the EU's Sixth Framework Programme (FP6), the XTREEMOS ('Building and promoting a Linux-based operating system to support virtual organisation for next generation grids') project has designed and integrated a platform of open source technologies to facilitate usage, management, scalability and programming. Due to end in May 2010 and coordinated by the France-based group Caisse des Dépôts et Consignation (CDC), XTREEMOS successfully provides new grid capabilities including simpler monitoring and job submission. It also offers virtual organisation management and a comprehensive security implementation. According to the partners, XTREEMOS is available in three 'flavours': PC, XTREEMOS cluster, and XTREEMOS Mobile. The PC flavour allows for aggregating standalone PCs (personal computers) as computation resources into XTREEMOS grids. The XTREEMOS cluster is based on Kerrighed's Linux SSI (single-system image) technology, which is a Linux cluster that enables users to obtain an image of a single large system. XTREEMOS Mobile enables XtreemOS services to be run on mobile devices including Nokia Internet Tablets. The latest 2.0 release version includes several functionalities: (1) creation and management of dynamic virtual organisations, (2) application execution management, (3) XtreemFS, (4) XOSAGA programming interface, and (5) Xosautoconfig. The first one focuses on security infrastructure ensuring the secure operation of the system, while the second allows searches for available nodes that meet the application needs of candidates, and then executes the application on the selected nodes. XtreemFS enables installation scalability by adding machines with free storage resources, XOSAGA programming interface provides access to XTREEMOS resources and services, and Xosautoconfig supports grid administrators and other users in their efforts to deploy XTREEMOS nodes on virtual machines, grids and test beds quickly. Interested users can download the second public version on XTREEMOS' website. The source code, sample applications and demos are also available online. The XtreemOS partners are from China, France, Germany, Italy, the Netherlands, Slovenia, Spain and the UK.
Quality validation date: 2009-12-09

European LeukemiaNet takes cancer research to new heights

European researchers are steadfast in their efforts to improve the care of patients suffering from leukaemia. However, an EU-funded team of researchers is raising the bar by integrating the work of leading trial groups, their partner groups, industry and small to medium-sized enterprises (SMEs) across Europe to establish a cooperative network for advancements in leukaemia-related research and healthcare. The ultimate objective of the 'European LeukemiaNet' (ELN) project, which is funded under the EU's Sixth Framework Programme to the tune of EUR 6 million, is the launching of the European Leukaemia Trial Registry. The project was recently presented in Cancerworld magazine. Since the start of 2009, the ELN ('Strengthen and develop scientific and technological excellence in research and therapy of leukaemia (CML, AML, ALL, CLL, MDS, CMPD) by integration of the leading national leukaemia networks and their interdisciplinary partner groups in Europe') partners have succeeded in bringing together national leukaemia study groups consisting of 147 institutions in 28 countries. On the whole, over 1,000 researchers and around 10,000 patients are participating in the study. The ELN consortium has already implemented new treatment guidelines, made substantial progress with standardising monitoring techniques and initiated several clinical trials and registries for certain leukaemias. An annual symposium with impressive participation numbers also got off the ground. ELN is being coordinated by the Mannheim Medical Faculty of the University of Heidelberg in Germany, and Professor Rüdiger Hehlmann is leading the team. The project is modelled on a German Competence Network for acute and chronic leukaemias, which received nearly EUR 12 million in financial support from Germany's Ministry of Research and Education. The objective of the Competence Network was to address the deficiencies found in research and healthcare, such as duplication and fragmentation of clinical trials, and lack of definitions and standards for diagnostics and therapeutic criteria. In an editorial published in the journal Leukemia in 2004, Professor Hehlmann and colleagues wrote that the Competence Network targeted the support of excellence in research and care and sought to 'incorporate insights from gene array research into clinical practice, and to migrate rapidly to molecular classification of leukaemias. The network offers a competitive advantage for participating doctors and scientists from Germany and neighbouring countries.' Thanks to ELN, this advantage will be extended to more countries. The project comprises 16 Work Packages (WPs) targeting the integration of 95 leukaemia trial groups (covering all leukaemia types), their 102 interdisciplinary partner groups (e.g. diagnostics, treatment, guidelines) and industry. Six of the WPs are for clinical trials for disease types: acute lymphoblastic leukaemia (ALL), acute myeloblastic leukaemia (AML), chronic myeloid leukaemia (CML), chronic lymphoblastic leukaemia (CLL), chronic myeloproliferative diseases (CMPDs) and myelodysplastic syndromes (MDSs). The remaining packages cover interdisciplinary topics. ELN has also established a network management centre, and communication and information technology support is available. The ELN project has its roots in existing European support groups, including those for CML, but it has successfully expanded the number of participating countries, said Dr Susanne Saussele, ELN's scientific network manager. 'We have over 20 now for CML, more than double the original number, and the new participants include several from eastern Europe,' noted Dr Saussele, an oncologist at the University of Heidelberg. ELN is making huge strides in the development of a content management system for its website, enabling project details like papers, reports and contacts to be accessible. Project partners are from Austria, Belarus, Belgium, Croatia, Cyprus, the Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Latvia, Lithuania, Luxembourg, the Netherlands, Norway, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, the UK and Ukraine.
Quality validation date: 2009-12-08