Pierre-and-Marie-Curie University

About: Pierre-and-Marie-Curie University is a education organization based out in Paris, France. It is known for research contribution in the topics: Population & Raman spectroscopy. The organization has 34448 authors who have published 56139 publications receiving 2392398 citations.

Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity.

Abstract: Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and first invade the liver of the mammalian host, as an obligatory step of the life cycle of the malaria parasite. Within hepatocytes, Plasmodium sporozoites reside in a membrane-bound vacuole, where they differentiate into exoerythrocytic forms and merozoites that subsequently infect erythrocytes and cause the malaria disease. Plasmodium sporozoite targeting to the liver is mediated by the specific binding of major sporozoite surface proteins, the circumsporozoite protein and the thrombospondin-related anonymous protein, to glycosaminoglycans on the hepatocyte surface. Still, the molecular mechanisms underlying sporozoite entry and differentiation within hepatocytes are largely unknown. Here we show that the tetraspanin CD81, a putative receptor for hepatitis C virus, is required on hepatocytes for human Plasmodium falciparum and rodent Plasmodium yoelii sporozoite infectivity. P. yoelii sporozoites fail to infect CD81-deficient mouse hepatocytes, in vivo and in vitro, and antibodies against mouse and human CD81 inhibit in vitro the hepatic development of P. yoelii and P. falciparum, respectively. We further demonstrate that the requirement for CD81 is linked to sporozoite entry into hepatocytes by formation of a parasitophorous vacuole, which is essential for parasite differentiation into exoerythrocytic forms.

Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial

Abstract: Summary Background No effective standard treatment exists for patients with radioiodine-refractory, advanced differentiated thyroid carcinoma. We aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting. Methods In this randomised, double-blind, phase 2 trial, we enrolled adults (aged ≥18 years) with locally advanced or metastatic differentiated thyroid carcinoma (papillary, follicular, or poorly differentiated) at 16 European medical centres. Eligible patients were sequentially randomised in a 1:1 ratio with a standard computerised scheme to receive either vandetanib 300 mg per day (vandetanib group) or matched placebo (placebo group), balanced by centre. The primary endpoint was progression-free survival (PFS) in the intention-to-treat population based on investigator assessment. This study is registered with ClinicalTrials.gov, number NCT00537095. Findings Between Sept 28, 2007, and Oct 16, 2008, we randomly allocated 72 patients to the vandetanib group and 73 patients to the placebo group. By data cutoff (Dec 2, 2009), 113 (78%) patients had progressed (52 [72%] patients in the vandetanib group and 61 [84%] in the placebo group) and 40 (28%) had died (19 [26%] patients in the vandetanib group and 21 [29%] in the placebo group). Patients who received vandetanib had longer PFS than did those who received placebo (hazard ratio [HR] 0·63, 60% CI 0·54–0·74; one-sided p=0·008): median PFS was 11·1 months (95% CI 7·7–14·0) for patients in the vandetanib group and 5·9 months (4·0–8·9) for patients in the placebo group. The most common grade 3 or worse adverse events were QTc prolongation (ten [14%] of 73 patients in the vandetanib group vs none in the placebo group), diarrhoea (seven [10%] vs none), asthenia (five [7%] vs three [4%]), and fatigue (four [5%] vs none). Two patients in the vandetanib group and one in the placebo group died from treatment-related serious adverse events (haemorrhage from skin metastases and pneumonia in the vandetanib group and pneumonia in the placebo group). Interpretation Vandetanib is the first targeted drug to show evidence of efficacy in a randomised phase 2 trial in patients with locally advanced or metastatic differentiated thyroid carcinoma. Further investigation of tyrosine-kinase inhibitors in this setting is warranted. Funding AstraZeneca.

Protostellar disk formation and transport of angular momentum during magnetized core collapse

Abstract: Context. Theoretical studies of collapsing clouds have found that even a relatively weak magnetic field may prevent the formation of disks and their fragmentation. However, most previous studies have been limited to cases where the magnetic field and the rotation axis of the cloud are aligned.Aims. We study the transport of angular momentum, and its effects on disk formation, for non-aligned initial configurations and a range of magnetic intensities.Methods. We perform three-dimensional, adaptive mesh, numerical simulations of magnetically supercritical collapsing dense cores using the magneto-hydrodynamic code Ramses. We compute the contributions of all the relevant processes transporting angular momentum, in both the envelope and the region of the disk. We clearly define centrifugally supported disks and thoroughly study their properties.Results. At variance with earlier analyses, we show that the transport of angular momentum acts less efficiently in collapsing cores with non-aligned rotation and magnetic field. Analytically, this result can be understood by taking into account the bending of field lines occurring during the gravitational collapse. For the transport of angular momentum, we conclude that magnetic braking in the mean direction of the magnetic field tends to dominate over both the gravitational and outflow transport of angular momentum. We find that massive disks, containing at least 10% of the initial core mass, can form during the earliest stages of star formation even for mass-to-flux ratios as small as three to five times the critical value. At higher field intensities, the early formation of massive disks is prevented. Conclusions. Given the ubiquity of Class I disks, and because the early formation of massive disks can take place at moderate magnetic intensities, we speculate that for stronger fields, disks will form later, when most of the envelope will have been accreted. In addition, we speculate that some observed early massive disks may actually be outflow cavities, mistaken for disks by projection effects.

Monge-Ampère equations in big cohomology classes

Abstract: We define non-pluripolar products of an arbitrary number of closed positive (1, 1)-currents on a compact Kahler manifold X. Given a big (1, 1)-cohomology class α on X (i.e. a class that can be represented by a strictly positive current) and a positive measure μ on X of total mass equal to the volume of α and putting no mass on pluripolar sets, we show that μ can be written in a unique way as the top-degree self-intersection in the non-pluripolar sense of a closed positive current in α. We then extend Kolodziedj’s approach to sup-norm estimates to show that the solution has minimal singularities in the sense of Demailly if μ has L1+e-density with respect to Lebesgue measure. If μ is smooth and positive everywhere, we prove that T is smooth on the ample locus of α provided α is nef. Using a fixed point theorem, we finally explain how to construct singular Kahler–Einstein volume forms with minimal singularities on varieties of general type.