Gan Q.,University of Bordeaux Segalen
Nature Nanotechnology | Year: 2017
At the molecular level, translation refers to the production of a new entity according to a template that has a different chemical composition. In this way, chemical information may be translated from one molecule to another. The process is useful to synthesize structures and thus functions that might be difficult to create otherwise, and it reaches exquisite levels of efficiency in biological systems, as illustrated by protein expression from mRNA templates or by the assembly of the tobacco mosaic virus capsid protein according to the length of its RNA. In synthetic systems, examples of template-directed syntheses are numerous, but general and versatile schemes in which a non-natural sequence actually encodes the information necessary to produce a different sequence are few and far from being optimized. Here we show a high-fidelity enzyme-free translation of long rod-like alkylcarbamate oligomers into well-defined sequences of stacked helical aromatic oligoamides. The features present in the rods, which include the number and distance between carbamate functions and stereogenic centres, template the self-assembly of complementary stacks of helices that each have a defined right (P) or left (M) handedness, length and single or double helicity. This process enables the production of very large (>20 kDa) abiotic artificial folded architectures (foldamers) that may, for example, serve as scaffolds to organize appended functional features at positions in space defined with atomic precision across nanometric distances. © 2017 Nature Publishing Group
Ahmed S.H.,University of Bordeaux Segalen |
Ahmed S.H.,University of Bordeaux 1
Neuroscience and Biobehavioral Reviews | Year: 2010
In standard drug self-administration settings, animals have no choice than drug use. As a result, serious doubt exists about the interpretation of drug use in experimental animals. Is it symptomatic of an underlying addiction state or merely an expectable response to lack of choice? This incertitude in turn casts a shadow over many behavioral and neurobiological changes that have been well documented in animals following extended drug self-administration. Do they reflect pathological dysfunctions or normal neurobiological adaptations? Here I address these questions by focusing on intravenous cocaine self-administration in the rat as a paradigm example. Overall, available evidence shows that when a valuable behavioral option, even a biologically or physiologically inessential one, is made available during access to cocaine self-administration, most rats readily abstain from cocaine use in favor of the alternative reward regardless of the amount of past cocaine use. Only a small minority of rats continue to self-administer the drug despite the opportunity of making a different choice. This pattern of results (i.e., abstinence in most rats; cocaine preference in few rats) maps well onto what is currently known about the epidemiology of human cocaine addiction. It is thus possible that the minority of cocaine-preferring rats would be homologous to the minority of human cocaine users with a diagnosis of addiction while the remaining majority of abstinent rats would be resilient to cocaine addiction. Choice could represent an objective method of selection of addicted animals for future research on the neurobiological dysfunctions that are hypothesized to underlie cocaine addiction. Other competing interpretations of the same pattern of results are also discussed at the end of this review. © 2010 Elsevier Ltd.
Bouzier-Sore A.-K.,University of Bordeaux Segalen |
Pellerin L.,University of Lausanne
Frontiers in Cellular Neuroscience | Year: 2013
Since the initial description of astrocytes by neuroanatomists of the nineteenth century, a critical metabolic role for these cells has been suggested in the central nervous system. Nonetheless, it took several technological and conceptual advances over many years before we could start to understand how they fulfill such a role. One of the important and early recognized metabolic function of astrocytes concerns the reuptake and recycling of the neurotransmitter glutamate. But the description of this initial property will be followed by several others including an implication in the supply of energetic substrates to neurons. Indeed, despite the fact that like most eukaryotic non-proliferative cells, astrocytes rely on oxidative metabolism for energy production, they exhibit a prominent aerobic glycolysis capacity. Moreover, this unusual metabolic feature was found to be modulated by glutamatergic activity constituting the initial step of the neurometabolic coupling mechanism. Several approaches, including biochemical measurements in cultured cells, genetic screening, dynamic cell imaging, nuclear magnetic resonance spectroscopy and mathematical modeling, have provided further insights into the intrinsic characteristics giving rise to these key features of astrocytes. This review will provide an account of the different results obtained over several decades that contributed to unravel the complex metabolic nature of astrocytes that make this cell type unique. © 2013 Bouzier-Sore and Pellerin.
Herve P.Y.,University of Bordeaux Segalen
Trends in cognitive sciences | Year: 2013
Hemispheric specialization (HS) is a hemisphere-dependent relationship between a cognitive, sensory, or motor function and a set of brain structures. It includes both the hosting by a given hemisphere of specialized networks that have unique functional properties and mechanisms that enable the inter-hemispheric coordination necessary for efficient processing. Long derived from neuropsychological and behavioral observations, knowledge of HS is currently being profoundly modified by cutting-edge neuroimaging research that focuses both on the neural implementation of HS for language, visuospatial functions, and motor control/handedness across development and on the analysis of interactions between brain regions within and across hemispheres. New findings reveal the fundamental role of lateralization in the large-scale architecture of the human brain, whose ontogenesis has begun to be investigated with genetic-heritability brain mapping. Copyright © 2012 Elsevier Ltd. All rights reserved.
Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2013-IRSES | Award Amount: 831.10K | Year: 2014
The overall aim of the proposed staff exchange programme is to establish a long lasting collaboration between Moroccan, South African and European research teams involved in clinical epidemiological and public health research. This effort should ultimately lead to improved mother and child health and better control of sexual transmitted diseases. The proposal is therefore structured in seven work packages: 1. Management and coordination 2. Maternal & newborn health research 3. STI research 4. HPV research 5. Antibiotic resistance 6. Public Health and Social Health Protection 7. Clinical, epidemiological and public health research This project will brings partners together from Europe, Morocco and South Africa that have common research interests but that work in very different settings. Several partners have already been collaborating with each other but mainly on an ad hoc basis and not as a network: 1. The International Health Research Centre of Barcelona (CRESIB), Spain 2. The Institute of Tropical Medicine (ITM), Antwerp, Belgium 3. University Mohamed V Soussi Rabat, Morocco 4. University Sidi Mohamed Ben Abdellah of Fez, Morocco 5. University of Marrakech, Morocco 6. The Ministry of Health of Morocco - National Institute of Health Administration (INAS) 7. University of KwaZulu-Natal (UKZN), South Africa 8. University of Southampton, United Kingdom 9. The Bordeaux School of Public Health (ISPED), University Bordeaux Segalen, France For European researchers and professionals, the interaction with Moroccan and South African national health systems and research groups can contribute to a better understanding of common health challenges, including health related topics with human mobility and migrations between both continents and access to care for migrant groups in Europe. This collaboration involving several high profile groups (Europe, Morocco, South Africa) strengthens a global perspective on key maternal, newborn and reproductive health topics.
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2012.1.2-04 | Award Amount: 8.49M | Year: 2013
The strategic goal of the project is to help the European vineyard sector facing the increasingly global competition by meeting: * Consumer demands for diversified high quality wines and concerns for food safety * Citizens requests for environment-friendly production systems involving decreased or no use of pesticides and spare of not renewable natural resources * Producers needs of plant material, tools and methods to help them cope with the negative impacts of climate change while responding to demands for quality, environmental friendliness and needs of profitability To reach this overall goal, the project will: * At the plant level, improve and design agricultural practices (canopy management, irrigation, fertilisation, training systems, pest and disease control, etc.) aimed at maximising berry quality, durable resistance to pests and and diseases, and adaptation to climate change (higher CO2, drought, UV light, and higher temperatures) * At the vineyard level, design, develop and test innovative agronomic systems integrating new agricultural practices and taking into account the variability of constraints met by European vineyards grown under a wide range of environments * At the breeding level, diversify grapevine varieties with regard to desirable adaptative traits building on tools and knowledge developed through international breeding and genomic initiatives. The project will combine short, medium, and long-term approaches to respectively conceive innovative viticulture systems, design and test novel agronomic practices and decision support systems, and exploit the genetic diversity of grapevine that all together will ensure a progress towards sustainable viticulture.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-5 | Award Amount: 7.81M | Year: 2013
Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs (ncRNAs) regulate both immune and neuronal processes. Therefore, ncRNAPain proposes that ncRNAs are critically important master switches for chronic pain. ncRNAPain represents a multidisciplinary consortium of clinical partners, molecular and systems-level neuroscientists, bioinformatics and ncRNA experts. In order to gain knowledge on the mechanisms of chronic pain, ncRNAPain will investigate ncRNAs specifically in neurogenic and neuropathic pain, including headache. ncRNAPain will provide novel understanding of ncRNA regulation of processes modulating nociception and endogenous analgesia and of the importance of ncRNAs in circuitries and cognitive, emotional and behavioural components of pain. ncRNAPain will reveal insights into the concerted function of ncRNAs in the control of macromolecular complexes in neurons, glia and immune cells and signals used for neuroimmune communication in the pain pathway. Based on these findings, ncRNAPain will identify and validate specific ncRNAs as new druggable molecular targets for pain prevention and relief. ncRNAPain will identify pain predisposing ncRNA expression patterns and polymorphisms in ncRNAS and/or their binding sites as biomarkers for pain and inter-individual variations in the response to painful stimuli and analgesic drugs. ncRNA-based diagnostic tools will be developed and provided to enable better patient stratification, improved mechanism-based treatment and targeted prevention strategies for high risk individuals. ncRNAPain will provide novel understanding of the induction and maintenance of chronic pain and is committed to translate pre-clinical and clinical results and developments into clinical applications for the benefit of the patients, to improve the patients quality of life and reduce the societal burden of chronic pain across Europe.
Nanobiotix, French National Center for Scientific Research and University of Bordeaux Segalen | Date: 2015-10-19
The present application relates to a method of monitoring the membrane permeabilization of liposome and the incidental release of a compound of interest.
Saupe S.J.,University of Bordeaux Segalen
Seminars in Cell and Developmental Biology | Year: 2011
[Het-s] is a prion from the filamentous fungus Podospora anserina and corresponds to a self-perpetuating amyloid aggregate of the HET-s protein. This prion protein is involved in a fungal self/non-self discrimination process termed heterokaryon incompatibility corresponding to a cell death reaction occurring upon fusion of genetically unlike strains. Two antagonistic allelic variants of this protein exist: HET-s, the prion form of which corresponds to [Het-s] and HET-S, incapable of prion formation. Fusion of a [Het-s] and HET-S strain triggers the incompatibility reaction, so that interaction of HET-S with the [Het-s] prion leads to cell death. HET-s and HET-S are highly homologous two domain proteins with a N-terminal globular domain termed HeLo and a C-terminal unstructured prion forming domain (PFD). The structure of the prion form of the HET-s PFD has been solved by solid state NMR and corresponds to a very well ordered β-solenoid fold with a triangular hydrophobic core. The ability to form this β-solenoid fold is retained in a distant homolog of HET-s from another fungal species. A model for the mechanism of [Het-s]/HET-S incompatibility has been proposed. It is believe that when interacting with the [Het-s] prion seed, the HET-S C-terminal region adopts the β-solenoid fold. This would act as a conformational switch to induce refolding and activation of the HeLo domain which then would exert its toxicity by a yet unknown mechanism. © 2011 Elsevier Ltd.
Ravaud A.,University of Bordeaux Segalen
The oncologist | Year: 2011
Targeted therapy for advanced renal cell carcinoma (RCC) has recently expanded the available treatment options for patients with these malignancies. The rapid introduction of novel treatment options into clinical practice within a relatively short time frame has created some new challenges pertaining to adverse event (AE) management in patients with advanced RCC. Accumulating safety data from the pivotal phase III clinical trials of the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab plus interferon, VEGF receptor tyrosine kinase inhibitors (sunitinib, sorafenib, and pazopanib), and mammalian target of rapamycin inhibitors (temsirolimus and everolimus) have served to characterize the toxicity profiles of these novel agents. Overall, it is evident that RCC-directed targeted therapy differs from immunotherapy and cytotoxic chemotherapy in terms of a number of unique nonhematologic AEs (some of which have not been traditionally encountered in oncology practice) and that there are distinctions within and across the various classes of agents with respect to the most prominent AEs and the risk for less common but serious complications. Although treatment-associated AEs are common, the majority of AEs reported during clinical trial experiences were grade 1 or 2 in severity and manageable with intervention in the form of supportive measures and/or dosage modification. Therefore, despite the relatively complex AE profiles of RCC-directed targeted therapy, patient education, consistent monitoring with a focus on early detection by health care providers (oncologists, general physicians, nurses), and the application of emerging AE management strategies may allow for prolonged treatment in most patients with advanced RCC.