Kernel Architecture of the Genetic Circuitry of the Arabidopsis Circadian System

A wide range of organisms features molecular machines, circadian clocks, which generate endogenous oscillations with ~24 h periodicity and thereby synchronize biological processes to diurnal environmental fluctuations. Recently, it has become clear that plants harbor more complex gene regulatory circuits within the core circadian clocks than other organisms, inspiring a fundamental question: are all these regulatory interactions between clock genes equally crucial for the establishment and maintenance of circadian rhythms? Our mechanistic simulation for Arabidopsis thaliana demonstrates that at least half of the total regulatory interactions must be present to express the circadian molecular profiles observed in wild-type plants. A set of those essential interactions is called herein a kernel of the circadian system. The kernel structure unbiasedly reveals four interlocked negative feedback loops contributing to circadian rhythms, and three feedback loops among them drive the autonomous oscillation itself. Strikingly, the kernel structure, as well as the whole clock circuitry, is overwhelmingly composed of inhibitory, rather than activating, interactions between genes. We found that this tendency underlies plant circadian molecular profiles which often exhibit sharply-shaped, cuspidate waveforms. Through the generation of these cuspidate profiles, inhibitory interactions may facilitate the global coordination of temporally-distant clock events that are markedly peaked at very specific times of day. Our systematic approach resulting in experimentally-testable predictions provides insights into a design principle of biological clockwork, with implications for synthetic biology.Comment: Supplementary material is available at the journal websit

SARNET - Severe Accident Research Network of Excellence

Fifty-one organisations network in SARNET (Severe Accident Research NETwork of Excellence) their research capacities in order to resolve the most important pending issues for enhancing, with regard to Severe Accidents (SA), the safety of existing and future Nuclear Power Plants (NPPs). This project, co-funded by the European Commission (EC) under the 6th Framework Programme, has been defined in order to optimise the use of the available means and to constitute sustainable research groups in the European Union. SARNET tackles the fragmentation that may exist between the different national R&D programmes, in defining common research programmes and developing common computer tools and methodologies for safety assessment. SARNET comprises most of the organisations involved in SA research in Europe, plus Canada. To reach these objectives, all the organisations networked in SARNET contributed to a Joint Programme of Activities, which consisted of: Implementation of an advanced communication tool for accessing all project information, fostering exchange of information, and managing documents; Harmonization and re-orientation of the research programmes, and definition of new ones; Analysis of the experimental results provided by research programmes in order to elaborate a common understanding of relevant phenomena; Development of the ASTEC code (integral computer code used to predict the NPP behaviour during a postulated SA), which capitalizes in terms of physical models the knowledge produced within SARNET; Development of Scientific Databases in which all the results of research programmes are stored in a common format (DATANET); Development of a common methodology for Probabilistic Safety Assessment of NPPs; Development of short courses and writing a text book on Severe Accidents for students and researchers; Promotion of personnel mobility amongst various European organisations. This paper presents the major achievements after four and a half years of operation of the network, in terms of knowledge gained, of improvement of the ASTEC reference code, of dissemination of results and of integration of the research programmes conducted by the various partners. After this first period (2004-2008), co-funded by the EC, a further contract SARNET2 with the EC for the next four years started in April 2009 as part of the 7th Framework Programme. During this period, the networking activities will focus mainly on the remaining pending issues as determined during the first period, experimental activities will be directly included in the common work and the network will evolve toward complete self-sustainability. The bases for such an evolution are presented in the last part of the paper.JRC.F.5-Safety of present nuclear reactor

SARNET a European Cooperative Effort on LWR Severe Accident Research

A number of European R&D organizations, including technical supports of safety authorities, industriy, utilities and universities, have decided to use the opportunity offered by EC in the framework of FP6 to network in the Severe Accident Research Network (SARNET) their capacities of research in the severe accident area and thus enhancing the safety of existing and future NPPs. The report describes the form and the status of the network./JRC.G.2-Support to external securit

Diets and enteral supplements for improving outcomes in chronic kidney disease.

Protein-energy wasting (PEW), which is manifested by low serum levels of albumin or prealbumin, sarcopenia and weight loss, is one of the strongest predictors of mortality in patients with chronic kidney disease (CKD). Although PEW might be engendered by non-nutritional conditions, such as inflammation or other comorbidities, the question of causality does not refute the effectiveness of dietary interventions and nutritional support in improving outcomes in patients with CKD. The literature indicates that PEW can be mitigated or corrected with an appropriate diet and enteral nutritional support that targets dietary protein intake. In-center meals or oral supplements provided during dialysis therapy are feasible and inexpensive interventions that might improve survival and quality of life in patients with CKD. Dietary requirements and enteral nutritional support must also be considered in patients with CKD and diabetes mellitus, in patients undergoing peritoneal dialysis, renal transplant recipients, and in children with CKD. Adjunctive pharmacological therapies, such as appetite stimulants, anabolic hormones, and antioxidative or anti-inflammatory agents, might augment dietary interventions. Intraperitoneal or intradialytic parenteral nutrition should be considered for patients with PEW whenever enteral interventions are not possible or are ineffective. Controlled trials are needed to better assess the effectiveness of in-center meals and oral supplements