The RIP140 Gene Is a Transcriptional Target of E2F1

RIP140 is a transcriptional coregulator involved in energy homeostasis and ovulation which is controlled at the transcriptional level by several nuclear receptors. We demonstrate here that RIP140 is a novel target gene of the E2F1 transcription factor. Bioinformatics analysis, gel shift assay, and chromatin immunoprecipitation demonstrate that the RIP140 promoter contains bona fide E2F response elements. In transiently transfected MCF-7 breast cancer cells, the RIP140 promoter is transactivated by overexpression of E2F1/DP1. Interestingly, RIP140 mRNA is finely regulated during cell cycle progression (5-fold increase at the G1/S and G2/M transitions). The positive regulation by E2F1 requires sequences located in the proximal region of the promoter (−73/+167), involves Sp1 transcription factors, and undergoes a negative feedback control by RIP140. Finally, we show that E2F1 participates in the induction of RIP140 expression during adipocyte differentiation. Altogether, this work identifies the RIP140 gene as a new transcriptional target of E2F1 which may explain some of the effect of E2F1 in both cancer and metabolic diseases

Pharmacokinetic analysis of mizolastine in healthy young volunteers after single oral and intravenous doses: noncompartmental approach and compartmental modeling

International audienceThis paper presents the analysis of the kinetics of a new antihistamine, mizolastine, in 18 healthy volunteers, from concentrations measured after an intravenous infusion and two different oral administrations: tablet and capsule. Two approaches were used to analyze these data: (i) a noncompartmental approach implemented in PHARM-NCA; (ii) a compartmental modeling approach implemented in a new S-PLUS library, NLS2, Which allows the estimation of variance parameters simultaneously with the kinetics parameters. For the compartmental modeling approach, two-compartment open models were used. According to the Akaike criterion, the best model describing the kinetics of mizolastine after oral administration was the zero-order absorption model. The kinetic parameters obtained with PHARM-NCA and NLS2 were similar. The estimated duration of absorption was greater for the tablets than for the capsules (with means equal to 1.13 hr and 0.84 hr respectively). After an intravenous infusion, the mean estimated clearance was 4.9 L:hr, the mean lambda_2-phase apparent volume of distribution was 89.6 L and the mean terminal half-life was 12.9 hr

Simulations of radical and ion fluxes on wafer in a Cl<SUB>2</SUB>/Ar ICP discharge : Confrontation with GaAs and GaN etch experiments

International audienceA two-dimensional fluid model is used to study an industrial Ar/Cl2 inductively coupled plasma discharge designed to etch III-V samples. The effect of rf power, gas pressure, and chlorine content on the fluxes of reactive species reaching the wafer is numerically investigated. To understand how the etch process is influenced by the discharge conditions, simulation results are confronted with GaAs and GaN etch experiments performed in the same reactor geometry. When the source power is increased, the measured etch rate increase is consistent with the Cl radical and ion fluxes increase shown in the simulation, as well as the ion energy decrease due to the constant value of the wafer-holder power. Increasing the gas pressure results in a moderate increase in the etch rate due to the lower magnitude, lower mean energy, and anisotropy of the ion flux at high pressure. When the chlorine content is increased, the total ion flux decreases while Cl and Cl2 neutral fluxes increase significantly. A good correlation is obtained between calculated fluxes and etch characteristics, analyzed with scanning electron microscope images of etch profiles

Growth and characterisation of single crystals of ternary chalcogenides for laser applications

Bulk single crystals up to 20 mm in diameter and 40 mm long for LiInS2 and up to 10 mm, 20 mm, respectively, for LiInSe2 have been grown. Their colour changed from colourless to rose for the first one and from yellow to dark red for the other All crystals have wurtzite-type lattice (Pna2(1) space group), lattice parameters were determined. A band gap was found to be 3.72 and 3.57 eV for LiInS2 and 3.02, 2.86 eV for LiInSe2 at 80 and 300 K, respectively. Colour variations are due to point defects, first of all to interstitial sulfur; resulting in additional wide absorption bands in the shortwave part of transparency range. For LiInS2 the SHG phase matching conditions were found to be similar for samples of different colour and some difference from Boyd\u27s predictions of 1973 was shown: for XY plane Delta phi similar to +3 degrees at 2.6 mum and Delta phi similar to +3 to -5 degrees at 4-5 mum. Nonlinear susceptibility for LiInS2 was estimated: d(eff)(XY) similar to3.4 pm/V relative to Boyd\u27s valise as 10.6 pm/V A proper illumination gives a photoinduced change of LiInSe2 colour from dark red to yellow as a result of changes in point defects charge state

A specific and unusual nuclear localization signal in the DNA binding domain of the Rev-erb orphan receptors

International audienc

Incidence of idiopathic nephrotic syndrome during the Covid-19 pandemic in the Paris area (France) and in the Netherlands

Background The aetiology of idiopathic nephrotic syndrome (INS) remains partially unknown. Viral infections have been associated with INS onset. Since we observed fewer first onset INS cases during the Covid-19 pandemic, we hypothesised that lower INS incidence was the result of lockdown measures. Therefore, the aim of this study was to evaluate the incidence of childhood INS before and during the COVID-19 pandemic in two independent European INS cohorts.Methods Children with new INS in the Netherlands (2018-2021) and Paris area (2018-2021) were included. We estimated incidences using census data for each region. Incidences were compared using two proportion Z-tests.Results A total of 128 and 324 cases of first onset INS were reported in the Netherlands and Paris area, respectively, corresponding to an annual incidence of 1.21 and 2.58 per 100,000 children/year. Boys and young children (< 7 years) were more frequently affected. Incidence before and during the pandemic did not differ. When schools were closed, incidence was lower in both regions: 0.53 vs. 1.31 (p = 0.017) in the Netherlands and 0.94 vs. 2.63 (p = 0.049) in the Paris area. During peaks of hospital admissions for Covid-19, no cases were reported in the Netherlands or Paris area.Conclusions Incidence of INS before and during the Covid-19 pandemic was not different, but when schools were closed during lockdown, incidence was significantly lower. Interestingly, incidences of other respiratory viral infections were also reduced as was air pollution. Together, these results argue for a link between INS onset and viral infections and/or environmental factors.IP1BImmunopathology of vascular and renal diseases and of organ and celltransplantatio

Meta-Analysis of Gastrointestinal Adverse Events from Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia

Tyrosine kinase inhibitors (TKIs) are the frontline therapy for BCR-ABL (Ph+) chronic myeloid leukemia (CML). A systematic meta-analysis of 43 peer-reviewed studies with 10,769 CML patients compared the incidence of gastrointestinal adverse events (GI AEs) in a large heterogeneous CML population as a function of TKI type. Incidence and severity of nausea, vomiting, and diarrhea were assessed for imatinib, dasatinib, bosutinib, and nilotinib. Examination of combined TKI average GI AE incidence found diarrhea most prevalent (22.5%), followed by nausea (20.6%), and vomiting (12.9%). Other TKI GI AEs included constipation (9.2%), abdominal pain (7.6%), gastrointestinal hemorrhage (3.5%), and pancreatitis (2.2%). Mean GI AE incidence was significantly different between TKIs (p &lt; 0.001): bosutinib (52.9%), imatinib (24.2%), dasatinib (20.4%), and nilotinib (9.1%). Diarrhea was the most prevalent GI AE with bosutinib (79.2%) and dasatinib (28.1%), whereas nausea was most prevalent with imatinib (33.0%) and nilotinib (13.2%). Incidence of grade 3 or 4 severe GI AEs was ≤3% except severe diarrhea with bosutinib (9.5%). Unsupervised clustering revealed treatment efficacy measured by the complete cytogenetic response, major molecular response, and overall survival is driven most by disease severity, not TKI type. For patients with chronic phase CML without resistance, optimal TKI selection should consider TKI AE profile, comorbidities, and lifestyle.</jats:p