The University of Lille Nord de France , located in Lille, France, is a center for higher education, academic research and doctoral studies located over multiple campuses in the Academie de Lille.It includes a doctoral college that federates university institutes, engineering schools and research centres. With more than one hundred thousand students, the Université Lille Nord de France is one of the five largest university federations in France. Wikipedia.
Hedoux A.,University of Lille Nord de France
Advanced Drug Delivery Reviews | Year: 2016
The success rate for drug discovery and the development of innovative therapeutic strategies are intimately related to the physical properties of the solid-state condensed matter, which have direct influence on the bioavailability of Active Pharmaceutical Ingredients. In order to transform a new molecule in efficient drug, the material is brought into an amorphous state using various manufacturing processes including freeze drying, spray drying, hot melt extrusion and loading in different delivery devices. The infrared and Raman spectroscopic analyses used for exploring disordered and amorphous states, for the monitoring of the drug physical stability in drug delivery systems are described in this review. © 2015 Elsevier B.V.
Gonzalez-Hilarion S.,University of Lille Nord de France
Orphanet journal of rare diseases | Year: 2012
Nonsense mutations are at the origin of many cancers and inherited genetic diseases. The consequence of nonsense mutations is often the absence of mutant gene expression due to the activation of an mRNA surveillance mechanism called nonsense-mediated mRNA decay (NMD). Strategies to rescue the expression of nonsense-containing mRNAs have been developed such as NMD inhibition or nonsense mutation readthrough. Using a dedicated screening system, we sought molecules capable to block NMD. Additionally, 3 cell lines derived from patient cells and harboring a nonsense mutation were used to study the effect of the selected molecule on the level of nonsense-containing mRNAs and the synthesis of proteins from these mutant mRNAs. We demonstrate here that amlexanox, a drug used for decades, not only induces an increase in nonsense-containing mRNAs amount in treated cells, but also leads to the synthesis of the full-length protein in an efficient manner. We also demonstrated that these full length proteins are functional. As a result of this dual activity, amlexanox may be useful as a therapeutic approach for diseases caused by nonsense mutations.
Popescu C.I.,University of Lille Nord de France
Biology of the cell / under the auspices of the European Cell Biology Organization | Year: 2010
HCV (hepatitis C virus) represents a major global health problem. A consistent body of evidence has been accumulating, suggesting a peculiar overlap between the HCV life cycle and lipid metabolism. This association becomes evident both for the clinical symptoms of HCV infection and the molecular mechanisms underlying the morphogenesis and entry process of this virus. The HCV core-lipid droplets association seems to be central to the HCV morphogenesis process. Moreover, the biogenesis pathway of very-low-density lipoproteins has been shown to be involved in HCV morphogenesis with MTP (microsomal triacylglycerol transfer protein), ApoB (apolipoprotein B) and ApoE (apolipoprotein E) as essential elements in the production of infectious HCV particles. HCV infectivity also correlates with the lipidation status of the particles. Furthermore, some HCV cellular receptors and the regulation of the entry process are also connected to lipoproteins and lipid metabolism. Specifically, lipoproteins modulate the entry process and the cholesterol transporter SR-BI (scavenger receptor class B type I) is a cellular entry factor for HCV. The present review aims to summarize the advances in our understanding of the HCV-lipid metabolism association, which may open new therapeutic avenues.
Breton C.,University of Lille Nord de France
Journal of Endocrinology | Year: 2013
Epidemiological studies initially demonstrated that maternal undernutrition leading to low birth weight may predispose for energy balance disorders throughout life. High birth weight due to maternal obesity or diabetes, inappropriate early post-natal nutrition and rapid catch-up growth may also sensitise to increased risk of obesity. As stated by the Developmental Origin of Health and Disease concept, the perinatal perturbation of foetus/neonate nutrient supply might be a crucial determinant of individual programming of body weight set point. The hypothalamus-adipose axis plays a pivotal role in the maintenance of energy homoeostasis controlling the nutritional status and energy storage level. The perinatal period largely corresponds to the period of brain maturation, neuronal differentiation and active adipogenesis in rodents. Numerous dams and/or foetus/neonate dietary manipulation models were developed to investigate the mechanisms underlying perinatal programming in rodents. These models showed several common offspring hypothalamic consequences such as impaired neurogenesis, neuronal functionality, nuclei structural organisation and feeding circuitry hardwiring. These alterations led to a persistent reprogrammed appetite system that favoured the orexigenic pathways, leptin/insulin resistance and hyperphagia. Impaired hypothalamic sympathetic outflow to adipose tissue and/or reduced innervation may also account for modified fat cell metabolism. Thus, enhanced adipogenesis and/or lipogenesis capacities may predispose the offspring to fat accumulation. Abnormal hypothalamus-adipose axis circadian rhythms were also evidenced. This review mainly focuses on studies in rodents. It highlights hormonal and epigenetic mechanisms responsible for long-lasting programming of energy balance in the offspring. Dietary supplementation may provide a therapeutic option using a specific regimen for reversing adverse programming outcomes in humans. © 2013 Society for Endocrinology.
Bako L.,University of Lille Nord de France
Automatica | Year: 2011
The work presented in this paper is concerned with the identification of switched linear systems from input-output data. The main challenge with this problem is that the data are available only as a mixture of observations generated by a finite set of different interacting linear subsystems so that one does not know a priori which subsystem has generated which data. To overcome this difficulty, we present here a sparse optimization approach inspired by very recent developments from the community of compressed sensing. We formally pose the problem of identifying each submodel as a combinatorial ℓ0 optimization problem. This is indeed an NP-hard problem which can interestingly, as shown by the recent literature, be relaxed into a (convex) ℓ1-norm minimization problem. We present sufficient conditions for this relaxation to be exact. The whole identification procedure allows us to extract the parameter vectors (associated with the different subsystems) one after another without any prior clustering of the data according to their respective generating-submodels. Some simulation results are included to support the potentialities of the proposed method. © 2011 Elsevier Ltd. All rights reserved.
Carnaille B.,University of Lille Nord de France
Langenbeck's Archives of Surgery | Year: 2012
Introduction: There are no randomised studies comparing open and laparoscopic approaches foradrenalectomy in patients with adrenal cortical carcinoma. Methods: There is evidence of postoperative benefit for the patients undergoing laparoscopic adrenalectomy compared to open adrenalectomy (level B). Results: Results from comparison of oncological outcomes in ACC between open and laparoscopic approaches are equivocal: increasedrisk of local recurrence and peritoneal carcinomatosis by the laparoscopic route (level D), and identical results between the two approaches in terms of survival, recurrence and peritoneal carcinomatosis (level C). Conclusion: An open approach is recommended in case of local invasion, with a view to achieving an R0 resection (level D). Laparoscopic resection of ACC/potentially malignant tumours, which includes removal of surrounding periadrenal fat and results in an R0 resection without tumour capsule rupture, may be performed for preoperative and intraoperative stage 1-2 ACC and tumours with a diameter <10 cm (level C). © Springer-Verlag 2011.
Belouzard S.,University of Lille Nord de France
Viruses | Year: 2012
Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes-A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.
Cordonnier C.,University of Lille Nord de France
Current Opinion in Neurology | Year: 2011
Purpose of review: Brain microbleeds (BMBs) are a radiological construct that is meant to represent a specific underlying microscopic pathology: perivascular collections of hemosiderin deposits. BMBs may represent two different types of underlying vasculopathies: hypertensive vasculopathy and cerebral amyloid angiopathy. This brief review highlights some recent works discussing their nature, and both their diagnostic and prognostic values. Recent findings: The improvement of detection techniques has modified our perception of BMBs prevalence, which can reach 35% among healthy people compared with 5% when conventional techniques are used. Our knowledge on BMBs is evolving very quickly. The careful study of their anatomical distribution sheds light on their histological significance: deep BMBs may represent hypertensive vasculopathies and lobar ones cerebral amyloid angiopathy. Summary: Despite an explosion of publications on BMBs, their diagnostic and prognostic values have only received indirect support and remain to be explored. To date, BMBs should not contraindicate antithrombotic treatment in settings wherein benefits have clearly been demonstrated in clinical trials and meta-analyses. One intriguing field is Alzheimer's disease, in which BMBs may be a missing link between two important theories on the neuropathogenesis of Alzheimer's disease: the amyloid cascade hypothesis and the vascular hypothesis. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.
de Reuck J.L.,University of Lille Nord de France
Aging and Disease | Year: 2012
Small cerebral bleeds are frequently observed in brains of patients with Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). However, they are also observed in patients with other neurodegenerative dementias and in persons without cognitive impairment. The aim of this survey is to compare the bleeding load in brains with different dementia syndromes and in age-matched controls. Hundred sixty-five brains were examined. The prevalence and the severity of the different cerebrovascular lesions were examined. Quantification of the number of mini-bleeds allowed to determinate the bleeding load in different cerebral regions. Micro-bleeds were considered as small macroscopically visible lesions while mini-bleeds were defined as small perivascular accumulations of red blood cells or siderophages only visible on microscopic examination. Several types of cerebrovascular lesions prevailed in AD brains with CAA, compared to the controls. White matter changes prevailed in frontotemporal lobar degeneration. Mini-bleeds were significantly more frequent in the cerebral cortex of AD and Lewy body dementia brains. They also prevailed around the dentate nucleus of the cerebellum and in the tegmentum pontis of patients with progressive supranuclear palsy. On the other hand the bleeding load in frontotemporal lobar degeneration and in corticobasal degeneration was similar to that in age-matched control brains. Cerebrovascular lesions, including micro-bleeds, predominated in AD brains with CAA. Mini-bleeds, on the other hand, were more related to the neurodegenerative process itself and reflected associated disruption of the blood-brain barrier.
Raibaut L.,University of Lille Nord de France |
Ollivier N.,University of Lille Nord de France |
Melnyk O.,University of Lille Nord de France
Chemical Society Reviews | Year: 2012
Total chemical synthesis of proteins is usually achieved by assembling unprotected peptide segments using site-specific and chemoselective native peptide ligation methods. Access to large proteins often requires the assembly of at least three segments due to the current limits of solid phase synthesis of individual peptide segments. The aim of this tutorial review is to present the basic concepts and challenges underlying the design of sequential peptide ligation strategies using solution or solid phase chemistry. A special emphasis is given to C-to-N and N-to-C three-segment assembly strategies, which potentially give access to proteins composed of up to 150 amino acid residues. © 2012 The Royal Society of Chemistry.