Attenuation of Soft-Tissue Sarcomas Resistance to the Cytotoxic Action of TNF-α by Restoring p53 Function

BACKGROUND: Isolated limb perfusion with TNF-α and melphalan is used with remarkable efficiency to treat unresectable limb sarcomas. Here we tested the ability of TNF-α to directly induce apoptosis of sarcoma cells. In addition, we investigated the impact of p53 in the regulation of such effect. METHODOLOGY/PRINCIPAL FINDINGS: We first analysed the ability of TNF-α to induce apoptosis in freshly isolated tumour cells. For this purpose, sarcoma tumours (n = 8) treated ex vivo with TNF-α were processed for TUNEL staining. It revealed substantial endothelial cell apoptosis and levels of tumour cell apoptosis that varied from low to high. In order to investigate the role of p53 in TNF-α-induced cell death, human sarcoma cell lines (n = 9) with different TP53 and MDM2 status were studied for their sensitivity to TNF-α. TP53(Wt) cell lines were sensitive to TNF-α unless MDM2 was over-expressed. However, TP53(Mut) and TP53(Null) cell lines were resistant. TP53 suppression in TP53(Wt) cell lines abrogated TNF-α sensitivity and TP53 overexpression in TP53(Null) cell lines restored it. The use of small molecules that restore p53 activity, such as CP-31398 or Nutlin-3a, in association with TNF-α, potentiated the cell death of respectively TP53(Mut) and TP53(Wt)/MDM2(Ampl). In particular, CP-31398 was able to induce p53 as well as some of its apoptotic target genes in TP53(Mut) cells. In TP53(Wt)/MDM2(Ampl) cells, Nutlin-3a effects were associated with a decrease of TNF-α-induced NF-κB-DNA binding and correlated with a differential regulation of pro- and anti-apoptotic genes such as TP53BP2, GADD45, TGF-β1 and FAIM. CONCLUSION/SIGNIFICANCE: More effective therapeutic approaches are critically needed for the treatment of unresectable limb sarcomas. Our results show that restoring p53 activity in sarcoma cells correlated with increased sensitivity to TNF-α, suggesting that this strategy may be an important determinant of TNF-α-based sarcomas treatment

Real-time automated image segmentation technique for cerebral aneurysm on reconfigurable system-on-chip

Cerebral aneurysm is a weakness in a blood vessel that may enlarge and bleed into the surrounding area, which is a life-threatening condition. Therefore, early and accurate diagnosis of aneurysm is highly required to help doctors to decide the right treatment. This work aims to implement a real-time automated segmentation technique for cerebral aneurysm on the Zynq system-on-chip (SoC), and virtualize the results on a 3D plane, utilizing virtual reality (VR) facilities, such as Oculus Rift, to create an interactive environment for training purposes. The segmentation algorithm is designed based on hard thresholding and Haar wavelet transformation. The system is tested on six subjects, for each consists 512 × 512 DICOM slices, of 16 bits 3D rotational angiography. The quantitative and subjective evaluation show that the segmented masks and 3D generated volumes have admitted results. In addition, the hardware implement results show that the proposed implementation is capable to process an image using Zynq SoC in an average time of 5.2 ms

Controverses dans l’enseignement de l’évolution. Questions de recherches sur les stratégies d’intervention en classe et dans la formation

Nous proposons une revue de questions de recherches pédagogiques et didactiques orientées sur l’enseignement de l’évolution face à des controverses. Nous précisons en quoi l’enseignement de l’évolution est considéré comme controversé. Nous présentons des études examinant cette question puis des travaux qui ont permis la mise en œuvre de dispositifs ou de stratégies prenant en compte des tensions possibles dans l’enseignement de l’évolution, en classe, en formation des enseignants ou comme propositions théoriques.This paper provides a review of research issues in pedagogy and didactics relative to the controversial teaching of evolution. The reason why this teaching is considered controversial is specified. The presentation of studies examining this issue is followed by the analysis of research works that have contributed to developing methods to take account of possible tensions in the teaching of evolution in class, during teacher training or simply as theoretical proposals.Wir bieten einen Überblick über pädagogische und didaktische Forschungsfragen an, was die Entwicklungslehre im Hinblick auf mögliche Kontroversen angeht. Wir erklären, in wie fern der Unterricht der Entwicklungslehre als kontrovers gilt. Wir stellen Studien vor, die sich mit dieser Frage beschäftigt haben sowie Arbeiten über die Umsetzung von Maßnahmen oder Strategien, die mögliche Spannungen im Unterricht der Entwicklungslehre berücksichtigen, sei es in der Klasse, in der Lehrerausbildung oder als theoretische Ansätze.Proponemos una revista de cuestiones de investigaciones pedagógicas y didácticas orientadas hacia la enseñanza de la evolución frente a algunas controversias. Precisamos en qué la enseñanza de la evolución es considerada como contravertida. Presentamos unos estudios que examinan esta cuestión y a continuación unos trabajos que han permitido la aplicación de dispositivos o de estrategias que toman en cuenta posibles tensiones en la enseñanza de la evolución, en el aula, en formación de los docentes o como propuestas teóricas

Rapid and inexpensive detection of common HBB gene mutations in Tunisian population by high-resolution melting analysis: Implication for molecular diagnosis

International audienceIn Tunisia, beta-thalassemia is a common hereditary disease with a carrying rate of 2.21%. Up to now, detection of responsible mutations was made by laborious, expensive, and/or time consuming methods. The aim of this study is to develop and validate a specific assay for detection of the two most frequent mutations in Tunisian population, the IVS-I-110 (G -> A)and Cd39 (C -> T) mutations. In this study, we optimize high resolution melting analysis (HRMA) conditions for these mutations, using control DNAs. Then, we evaluate the strength of this methodology by screening a cohort of patients with beta-thalassemia. All examined reference DNA samples were unambiguously distinguished from each other. For the blinded test, the results were completely compatible with direct sequencing, performed after the HRMA. As HRMA represents a highly sensitive and high-throughput gene scanning method, it can provide timely diagnosis at low cost for effective clinical management of beta-thalassemia

Phosphoric acid purification sludge: Potential in heavy metals and rare earth elements

International audienceThe present study was carried out to show the potential in heavy metals (HM) and the rare earth elements (REE) which presents the residues of phosphoric-acid(PA) purification. Three different cadmiferous solid residues (according to the nature of the purification process of the PA: BG, BC and BS) were collected from an industrial site located in the south of Tunisia. The mineralogical study showed the predominance of anhydrite, accompanied by quartz, malladrite; calcium sulfate hemihydrate and fluorapophyllite. The microanalysis showed (i) the association of cadmium and zinc, (ii) as well as the presence of associated REEs. The chemical analysis showed that (i) the calcium sulfate concentrations are majority in samples BS, BG and BC (44, 34 and 44%, respectively), (ii) significant concentrations of phosphoric acid (28, 18 and 21% P2O5, respectively), (iii) the HM: Cd, Zn, Cr, Ni, V, Cu, Pb, Co, Mo, Mn and U have proportion in the order of 0.1%. The concentrations of Cd, Zn and Cr are respectively in the order of: 230, 149 and 189 mg/kg for BS, 346, 243 and 153 mg/kg for BG and 183, 129 and 440 mg/kg for BC and (iv) the REEs: La, Ce, Nd, Eu, Y et Yb present considerable mass percentages able to reach 0.2%. A series of extraction tests was led on the cadmiferous sludges to evaluate the rates of HM (Cd, Zn) and REE dissolution, using two solvents (deionized water (DW) and aqueous sodium based alkaline metal solution). The results showed that the dissolution rates of Cd and Zn are respectively in the order of (12–29% and 41–45% for DW; 67–86% and 83–93% for Na2SO4 solution). The extractability of HM and REE is strongly influenced by pH, solvent nature and mineral load in the cadmiferous sludges. The water-soluble metals represent a significant mobile fraction, making the toxic elements more sensitive to mobilization processes, such as leaching and erosion. Whereas, the metals extractable by the Na2SO4 solution represent a very important exchangeable and “co-crystallization” fraction, which reflects the bioavailability of these metals

HB S [beta 6(A3)GLU -> VAL, GAG > GTG] AND beta-GLOBIN GENE CLUSTER HAPLOTYPE DISTRIBUTION IN MAURITANIA

International audienceOf 1050 Mauritanian blood donors screened from the two main racial groups, i.e., the Moors and Black Africans, 60 were found to carry Hb S [beta 6(A3) Glu -> Val, GAG>GTG], giving a global frequency of 5.71%. The prevalence observed in the Black African Mauritanians (10.69%) is almost five times that found in the Moor group (2.25%). Four of the five main beta(S) haplotypes were detected in this study: Senegal (77.8%), Benin (8.8%), Arab-Indian (5.5%) and Bantu (4.4%). These data showed that Hb S is a serious public health problem in Mauritania. They also confirm the ethnic heterogeneity of the Mauritanian population