University of Nice Sophia Antipolis

About: University of Nice Sophia Antipolis is a education organization based out in Nice, France. It is known for research contribution in the topics: Population & Stars. The organization has 10291 authors who have published 19964 publications receiving 680762 citations. The organization is also known as: UNS & University of Nice-Sophia Antipolis.

Hypoxia, cancer metabolism and the therapeutic benefit of targeting lactate/H+ symporters

Abstract: Since Otto Warburg reported the ‘addiction’ of cancer cells to fermentative glycolysis, a metabolic pathway that provides energy and building blocks, thousands of studies have shed new light on the molecular mechanisms contributing to altered cancer metabolism. Hypoxia, through hypoxia-inducible factors (HIFs), in addition to oncogenes activation and loss of tumour suppressors constitute major regulators of not only the “Warburg effect” but also many other metabolic pathways such as glutaminolysis. Enhanced glucose and glutamine catabolism has become a recognised feature of cancer cells, leading to accumulation of metabolites in the tumour microenvironment, which offers growth advantages to tumours. Among these metabolites, lactic acid, besides imposing an acidic stress, is emerging as a key signalling molecule that plays a pivotal role in cancer cell migration, angiogenesis, immune escape and metastasis. Although interest in lactate for cancer development only appeared recently, pharmacological molecules blocking its metabolism are already in phase I/II clinical trials. Here, we review the metabolic pathways generating lactate, and we discuss the rationale for targeting lactic acid transporter complexes for the development of efficient and selective anticancer therapies.

Monomeric G-Protein-Coupled Receptor as a Functional Unit

Abstract: Rhodopsin, the first purified G-protein-coupled receptor (GPCR), was characterized as a functional monomer 30 year ago, but dimerization of GPCRs recently became the new paradigm of signal transduction. It has even been claimed, on the basis of recent biophysical and biochemical studies, that this new concept could be extended to higher-order oligomerization. Here this view is challenged. The new studies of rhodopsin and other simple (class 1a) GPCRs solubilized in detergent are re-assessed and are compared to the earlier classical studies of rhodopsin and other membrane proteins solubilized in detergent. The new studies are found to strengthen rather than invalidate the conclusions of the early ones and to support a monomeric model for rhodopsin and other class 1a GPCRs. A molecular model is proposed for the functional coupling of a rhodopsin monomeric unit with a G-protein heterotrimer. This model should be valid even for GPCRs that exist as structural dimers.

Patterns of loosening of polyethylene keeled glenoid components after shoulder arthroplasty for primary osteoarthritis: results of a multicenter study with more than five years of follow-up.

Abstract: Background: The aim of this study was to radiographically analyze the long-term glenoid migration patterns following total shoulder arthroplasty to better understand the factors responsible for loosening. Methods: Complete radiographic follow-up of more than five years was available for 518 total shoulder arthroplasties performed for primary glenohumeral osteoarthritis with use of an anatomically designed prosthesis with a cemented, all-polyethylene, keeled glenoid component. Radiographs were assessed for humeral head subluxation, periprosthetic radiolucent lines, and shifting of the position of the glenoid component. The type of migration of the glenoid was defined according to the direction of tilt, or as subsidence in the case of medial migration. Results: Definite radiographic evidence of glenoid loosening was observed in 166 shoulders (32%) and was characterized by radiolucency of ≥2 mm over the entire bone-cement interface in thirty shoulders and by a migration of the glenoid component (shift or subsidence) in 136 shoulders. Three predominant patterns of migration of the glenoid component were observed: superior tilting in fifty-two shoulders (10%), subsidence in forty-one shoulders (7.9%), and posterior tilting in thirty-three shoulders (6.4%). Superior tilting of the glenoid was associated with three risk factors: low positioning of the glenoid component, superior tilt of the glenoid component on the immediate postoperative coronal plane radiographs, and superior subluxation of the humeral head (p < 0.05 for all). Subsidence of the glenoid component was associated with the use of reaming to optimize the seating and positioning of the glenoid component (p < 0.001). Posterior tilting of the glenoid component was associated with preoperative posterior subluxation (i.e., a Walch type-B glenoid) and with excessive reaming (p < 0.01 for both). Conclusions: The three patterns of migration observed in this study underscore the potential importance of the supporting bone beneath the glenoid component. In some shoulders, use of a keel or pegs to provide fixation of a polyethylene component in the absence of good support from subchondral bone may not be sufficient to resist compressive and eccentric forces, resulting in loosening. Preserving subchondral bone may be important for long-term longevity of the glenoid component. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Global Oscillations at Low Frequency from the SOHO mission (GOLF)

Abstract: The GOLF experiment on the SOHO mission aims to study the internal structure of the sun by measuring the spectrum of global oscillations in the frequency range 10−7 to 10−2 Hz. Bothp andg mode oscillations will be investigated, with the emphasis on the low order long period waves which penetrate the solar core. The instrument employs an extension to space of the proven ground-based technique for measuring the mean line-of-sight velocity of the viewed solar surface. By avoiding the atmospheric disturbances experienced from the ground, and choosing a non-eclipsing orbit, GOLF aims to improve the instrumental sensitivity limit by an order of magnitude to 1 mm s−1 over 20 days for frequencies higher than 2.10−4 Hz. A sodium vapour resonance cell is used in a longitudinal magnetic field to sample the two wings of the solar absorption line. The addition of a small modulating field component enables the slope of the wings to be measured. This provides not only an internal calibration of the instrument sensitivity, but also offers a further possibility to recognise, and correct for, the solar background signal produced by the effects of solar magnetically active regions. The use of an additional rotating polariser enables measurement of the mean solar line-of-sight magnetic field, as a secondary objective.