The Somatostatin Analogue Octreotide Inhibits Growth of Small Intestine Neuroendocrine Tumour Cells

Octreotide is a widely used synthetic somatostatin analogue that significantly improves the management of neuroendocrine tumours (NETs). Octreotide acts through somatostatin receptors (SSTRs). However, the molecular mechanisms leading to successful disease control or symptom management, especially when SSTRs levels are low, are largely unknown. We provide novel insights into how octreotide controls NET cells. CNDT2.5 cells were treated from 1 day up to 16 months with octreotide and then were profiled using Affymetrix microarray analysis. Quantitative real-time PCR and western blot analyses were used to validate microarray profiling in silico data. WST-1 cell proliferation assay was applied to evaluate cell growth of CNDT2.5 cells in the presence or absence of 1 mM octreotide at different time points. Moreover, laser capture microdissected tumour cells and paraffin embedded tissue slides from SI-NETs at different stages of disease were used to identify transcriptional and translational expression. Microarrays analyses did not reveal relevant changes in SSTR expression levels. Unexpectedly, six novel genes were found to be upregulated by octreotide: annexin A1 (ANXA1), rho GTPase-activating protein 18 (ARHGAP18), epithelial membrane protein 1 (EMP1), growth/differentiation factor 15 (GDF15), TGF-beta type II receptor (TGFBR2) and tumour necrosis factor (ligand) superfamily member 15 (TNFSF15). Furthermore, these novel genes were expressed in tumour tissues at transcript and protein levels. We suggest that octreotide may use a potential novel framework to exert its beneficial effect as a drug and to convey its action on neuroendocrine cells. Thus, six novel genes may regulate cell growth and differentiation in normal and tumour neuroendocrine cells and have a role in a novel octreotide mechanism system

Les points de convergence théorique entre la finance islamique et les théories financières conventionnelles

La succession des crises financières a démontré la fragilité du système financier actuel dans le monde entier. Un système caractérisé par un endettement parfois excessif, risqué, et la cupidité de certains acteurs financiers. De ce fait, les chercheurs se sont mobilisés pour trouver des alternatives pertinentes, susceptibles de proposer des solutions aux failles du système conventionnel actuel.Parmi les différents courants scientifiques qui ont abordé cette problématique, on distingue les travaux qui se sont inspirés des principes de la religion islamique. Cette branche des sciences économiques modernes vise à apporter une contribution riche à la finance mondiale, par la mise en place d’un cadre conceptuel et pratique de la finance participative.Cette communication vise à présenter une partie de l’étude théorique de mon sujet de recherche, portant sur la mise en place d’un processus d’investissement multicritère, pour un choix pertinent de portefeuilles financiers composés des actifs cotés à la bourse de Casablanca, et qui sont conformes aux principes d’investissement de Shari’ah islamique.Ainsi, l’analyse sera portée sur les convergences théoriques entre les principes de l’économie islamique et son application directe la finance islamique, et certaines théories économiques conventionnelles, en l’occurrence la théorie d’agence, la finance comportementale, l’investissement socialement responsable et la RSE

Comparison between PI and PR Current Controllers of a Grid- Connected Photovoltaic System Under Load Variation

This paper presents a current control technique for a three-phase grid-connected DC /AC inverter which is used in photovoltaic systems. A Proportional-Resonant (PR) controller is used for replacing the conventional Proportional-Integral (PI) controller in this system. By comparison with the conventional PI control method, the PR control can introduce an infinite gain at the fundamental frequency and hence can achieve zero steady-state error. The proposed model is based on two control loops: the first control loop regulates DC link voltage and the second one is used to keep the injected current to the grid in phase with the voltage by means of a Phase Locked Loop (PLL) in order to achieve a unit power factor and to adjust the output power as required. In order to examine the effectiveness of the suggested control, a simulation using the Matlab/Simulink software has been done and it’s concluded from the simulation results that the presented control by using the PR controller can be able to maintain maximum active power and to keep always a unity power factor despite variation load

SOCIETES DE FINANCEMENTS PARTICIPATIFS AU MAROC : HUB REGIONAL DE LA FINANCE ETHIQUE EN AFRIQUE

La succession des crises financières a démontré la fragilité du système financier actuel dans le monde entier. Un système caractérisé par un endettement parfois excessif, risqué, et la cupidité de certains acteurs financiers. De ce fait, les chercheurs se sont mobilisés pour trouver des alternatives pertinentes aux failles du système conventionnel actuel.Parmi les différents courants scientifiques qui ont abordé cette problématique, on distingue les travaux qui se sont inspirés des principes de la religion islamique. Ces travaux visent à apporter une contribution riche à la finance mondiale, par la mise en place d’un cadre conceptuel et pratique de la finance participative, afin d’apporter une contribution aux théories de l’investissement socialement responsable.Cette communication vise à présenter une partie de l’étude empirique de mon sujet de recherche doctorale, portant sur la mise en place d’un processus d’investissement multicritère, pour un choix de portefeuilles financiers composés des actions cotées à la bourse de Casablanca, et qui sont conformes aux principes d’investissement de Shari’ah islamique.De ce fait, l’analyse sera portée sur la présentation d’un processus multicritère de sélection des actions cotées en bourse, et les résultats de cette étude permettront d’orienter les investissements vers des cibles éthiques. Aussi ces résultats pourraient déboucher à des travaux pour la mise en place d’un indice participative au niveau de la bourse de Casablanca, et permettre au Maroc de se positionner comme un Hub régional pour la finance participative en Afrique

Paraneoplastic Antigen Ma2 Autoantibodies as Specific Blood Biomarkers for Detection of Early Recurrence of Small Intestine Neuroendocrine Tumors

Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs

An innate immune signature induced by AS01- or AS03-adjuvanted vaccines predicts the antibody response magnitude and quality consistently over time

BackgroundAntibody-mediated protection can depend on mechanisms varying from neutralization to Fc-dependent innate immune-cell recruitment. Adjuvanted vaccine development relies on a holistic understanding of how adjuvants modulate the quantity/titer and quality of the antibody response.MethodsA Phase 2 trial (ClinicalTrials.gov: NCT00805389) evaluated hepatitis B vaccines formulated with licensed adjuvants (AS01B, AS01E, AS03, AS04 or Alum) in antigen-naïve adults. The trial investigated the role of adjuvants in shaping antibody-effector functions, and identified an innate transcriptional response shared by AS01B, AS01E and AS03. We integrated previously reported data on the innate response (gene expression, cytokine/C-reactive protein levels) and on quantitative/qualitative features of the mature antibody response (Fc-related parameters, immunoglobulin titers, avidity). Associations between the innate and humoral parameters were explored using systems vaccinology and a machine-learning framework.ResultsA dichotomy in responses between AS01/AS03 and AS04/Alum (with the former two contributing most to the association with the humoral response) was observed across all timepoints of this longitudinal study. The consistent patterns over time suggested a similarity in the impacts of the two-dose immunization regimen, year-long interval, and non-adjuvanted antigenic challenge given one year later. An innate signature characterized by interferon pathway-related gene expression and secreted interferon-γ-induced protein 10 and C-reactive protein, which was shared by AS01 and AS03, consistently predicted both the qualitative antibody response features and the titers. The signature also predicted from the antibody response quality, the group of adjuvants from which the administered vaccine was derived.ConclusionAn innate signature induced by AS01- or AS03-adjuvanted vaccines predicts the antibody response magnitude and quality consistently over time

Transcription factor regulation can be accurately predicted from the presence of target gene signatures in microarray gene expression data

Deciphering transcription factor networks from microarray data remains difficult. This study presents a simple method to infer the regulation of transcription factors from microarray data based on well-characterized target genes. We generated a catalog containing transcription factors associated with 2720 target genes and 6401 experimentally validated regulations. When it was available, a distinction between transcriptional activation and inhibition was included for each regulation. Next, we built a tool (www.tfacts.org) that compares submitted gene lists with target genes in the catalog to detect regulated transcription factors. TFactS was validated with published lists of regulated genes in various models and compared to tools based on in silico promoter analysis. We next analyzed the NCI60 cancer microarray data set and showed the regulation of SOX10, MITF and JUN in melanomas. We then performed microarray experiments comparing gene expression response of human fibroblasts stimulated by different growth factors. TFactS predicted the specific activation of Signal transducer and activator of transcription factors by PDGF-BB, which was confirmed experimentally. Our results show that the expression levels of transcription factor target genes constitute a robust signature for transcription factor regulation, and can be efficiently used for microarray data mining

Hepatocyte MyD88 affects bile acids, gut microbiota and metabolome contributing to regulate glucose and lipid metabolism

OBJECTIVE: To examine the role of hepatocyte myeloid differentiation primary-response gene 88 (MyD88) on glucose and lipid metabolism. DESIGN: To study the impact of the innate immune system at the level of the hepatocyte and metabolism, we generated mice harbouring hepatocyte-specific deletion of MyD88. We investigated the impact of the deletion on metabolism by feeding mice with a normal control diet or a high-fat diet for 8 weeks. We evaluated body weight, fat mass gain (using time-domain nuclear magnetic resonance), glucose metabolism and energy homeostasis (using metabolic chambers). We performed microarrays and quantitative PCRs in the liver. In addition, we investigated the gut microbiota composition, bile acid profile and both liver and plasma metabolome. We analysed the expression pattern of genes in the liver of obese humans developing non-alcoholic steatohepatitis (NASH). RESULTS: Hepatocyte-specific deletion of MyD88 predisposes to glucose intolerance, inflammation and hepatic insulin resistance independently of body weight and adiposity. These phenotypic differences were partially attributed to differences in gene expression, transcriptional factor activity (ie, peroxisome proliferator activator receptor-α, farnesoid X receptor (FXR), liver X receptors and STAT3) and bile acid profiles involved in glucose, lipid metabolism and inflammation. In addition to these alterations, the genetic deletion of MyD88 in hepatocytes changes the gut microbiota composition and their metabolomes, resembling those observed during diet-induced obesity. Finally, obese humans with NASH displayed a decreased expression of different cytochromes P450 involved in bioactive lipid synthesis. CONCLUSIONS: Our study identifies a new link between innate immunity and hepatic synthesis of bile acids and bioactive lipids. This dialogue appears to be involved in the susceptibility to alterations associated with obesity such as type 2 diabetes and NASH, both in mice and humans

Global identification of genes and pathways regulated by Akt during activation of T helper cells

We previously demonstrated that Akt differentially modulated a subset of NF-kB target genes during T cell activation. In the current study, we further explored the broader effects of Akt inhibition on T cell gene induction. Global microarray analysis was used to characterize T helper cell transcriptional responses following antigen receptor stimulation in the absence or presence of Akti1/2 (an allosteric inhibitor which targets Akt1 and Akt2), to identify novel targets dependent upon Akt and obtain a more comprehensive view of Akt-sensitive genes in Th2 helper T cells. Pathway analysis of microarray data from a CD4+ Th2 T cell line revealed effects on gene networks involving ribosomal and T cell receptor signaling pathways associated with Akti1/2 treatment. Using real-time PCR analysis, we validated the differential regulation of several genes in these pathways, including Ier3, Il13, Egr1, Ccl1 and Ccl4, among others. Additionally, transcription factor target gene (TFactS) analysis revealed that NF-kB and Myc were the most significantly enriched transcription factors among Akt-dependent genes after T cell receptor and CD28 stimulation. Akt activation elicited increases in the enrichment of NF-kB- and Myc-targeted genes. The present study has identified a diverse set of genes, and possible mechanisms for their regulation, that are dependent on Akt during T cell activation