Cooperative binding of ApiAP2 transcription factors is crucial for the expression of virulence genes in Toxoplasma gondii

International audienceToxoplasma gondii virulence depends on the expression of factors packed into specific organelles such as rhoptry and microneme. Although virulence factor expression is tightly regulated, the molecular mechanisms controlling their regulation remain poorly understood. ApiAP2 are a family of conserved transcription factors (TFs) that play an important role in regulating gene expression in apicomplexan parasites. TgAP2XI-5 is able to bind to transcription-ally active promoters of genes expressed during the S/M phase of the cell cycle, such as virulence genes (rhoptries and micronemes genes). We identified proteins interacting with TgAP2XI-5 including a cell cycle-regulated ApiAP2 TF, TgAP2X-5. Using an inducible knock-down strategy and RNA-seq, we demonstrated that the level of expression of number of virulence factors transcripts is affected by the disruption of TgAP2X-5 expression. While TgAP2X-5 disruption has mild effect on parasite invasion, it leads to the strain avirulence in mice. To better understand the molecular mechanisms at stake, we investigated the binding of TgAP2XI-5 at promoters in the TgAP2X-5 mutant strain in a genome-wide assay. We show that disruption of TgAP2X-5 expression leads to defects in TgAP2XI-5 binding to multiple rhoptry gene promoters. Taken together, these data suggest a cooperative contribution of two ApiAP2 TF in the regulation of virulence genes in T. gondii

Experimental procedure to design stressed HBAR devices when the third-order elastic constants are not known

International audienceVibration sensitivity is an important specification for oscillators dedicated to space or airborne systems. For some crystallographic material, some physical constant are not yet measured. So, computation of stress coefficients of frequency is not possible. This paper presents a simple experimentation which allows the determination of the six stress coefficients of frequency for each high-overtone bulk acoustic resonators configuration. The first three coefficient are sαmn are -2.9×10-12/Pa, 4.3×10-10/Pa and 9.4×10-11/Pa. The relative standard deviation can be high due to experimental uncertainty

New Radio-Frequency resonators based on Periodically Poled Lithium Niobate thin film and ridge structures

International audienceIn this paper, we present new results on the development of an original acoustic waveguides concept based on a Periodically Poled Lithium Niobate transducer. Periodically poled transducers have been investigated recently as an alternative to classical inter-digital transducers for the excitation and detection of guided acoustic waves. We expose here two different structures of RF resonators based on this concept: a “Silicon/Gold layer/PPLN thin film/Gold layer/Silicon” stack and a PPLN-ridge structure. Simulations, fabrication and experimental results of both resonators are presented. “Si/10 μm-thick PPLN/Si” and “PPLN-ridge (11 μm-wide and 250 μm-deep)” resonators with a poling period of 50 μm have been achieved. The experimental admittances of these devices have pointed out the existence of an isolated mode operating at frequencies near 110 MHz for the stack structure and near 160 MHz with an electromechanical coupling of about 19 % for the ridge structure. These results are in agreement with the finite and boundary elements simulations

TgAP2IX-5 is a key transcriptional regulator of the asexual cell cycle division in Toxoplasma gondii

International audienceApicomplexan parasites have evolved efficient and distinctive strategies for intracellular replication where the timing of emergence of the daughter cells (budding) is a decisive element. However, the molecular mechanisms that provide the proper timing of parasite budding remain unknown. Using Toxoplasma gondii as a model Apicomplexan, we identified a master regulator that controls the timing of the budding process. We show that an ApiAP2 transcription factor, TgAP2IX-5, controls cell cycle events downstream of centrosome duplication. TgAP2IX-5 binds to the promoter of hundreds of genes and controls the activation of the budding-specific cell cycle expression program. TgAP2IX-5 regulates the expression of specific transcription factors that are necessary for the completion of the budding cycle. Moreover, TgAP2IX-5 acts as a limiting factor that ensures that asexual proliferation continues by promoting the inhibition of the differentiation pathway. Therefore, TgAP2IX-5 is a master regulator that controls both cell cycle and developmental pathways

Cells derived from regenerated endothelium of the porcine coronary artery contain more oxidized forms of apolipoprotein-B-100 without a modification in the uptake of oxidized LDL

Increased accumulation of lipoproteins and cholesterol within cells from regenerated endothelium may be responsible for their reported dysfunction. This study compared the presence and uptake of oxidized forms of low-density lipoprotein (LDL) in cells derived from native and regenerated endothelium. Four weeks after balloon denudation, primary cultures of native and regenerated endothelial cells were prepared from porcine coronary arteries. Regenerated endothelium stained more strongly using an antibody against oxidized lipoproteins. The increase in oxidized forms of apolipoprotein-B-100 exhibited by cells from regenerated endothelium was not due to an increase in extracellular-induced oxidation of native LDL, measured as the production of thiobarbituric-acid-reactive substances, being identical in both cell types. Intracellular cholesterol and cholesterol ester content were unchanged in regenerated cells. Using flow cytometry, accumulation of oxidized LDL was investigated further by quantifying the uptake of a mildly oxidized preparation of 1,1’-dioctadecyl-3,3,3’,3-tetramethyl-indocarbocyanine perchlorate-labelled LDL. The parameters of uptake, EC50 and Emax, were not different between cells from native and regenerated endothelium suggesting that the number of LOX-1 receptors was identical in the two cell types. Moreover, a negative correlation between the increased uptake of acetylated LDL and decreased cGMP production in response to bradykinin was observed in cells from regenerated endothelium. Thus, the increased incorporation of modified LDL and their intracellular oxidation could be responsible for the alteration in NO production. The presence of oxidized forms of LDL may be a marker of endothelium regeneration and could be involved in the endothelial dysfunction of pig coronary arteries 4 weeks after balloon denudation

HBAR: High-Q, Low TCF resonators and low phase noise, low-g oscillators

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Selenoprotein T is a PACAP-regulated gene involved in intracellular Ca2+ mobilization and neuroendocrine secretion.

International audienceSelenoproteins contain the essential trace element selenium, the deficiency of which is associated with cancer or accelerated aging. Although selenoproteins are thought to be instrumental for the effects of selenium, the biological function of many of these proteins remains unknown. Here, we studied the role of selenoprotein T (SelT), a selenocysteine (Sec) -containing protein with no known function, which we have identified as a novel target gene of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) during PC12 cell differentiation. SelT was found to be ubiquitously expressed throughout embryonic development and in adulthood in rat. Immunocytochemical analysis revealed that SelT is mainly localized to the endoplasmic reticulum through a hydrophobic domain. PACAP and cAMP induced a rapid and long-lasting increase in SelT gene expression in PC12 cells, in a Ca(2+)-dependent manner. These results suggested a possible role of SelT in PACAP signaling during PC12 cell differentiation. Indeed, overexpression of SelT in PC12 cells provoked an increase in the concentration of intracellular Ca(2+) ([Ca(2+)](i)) that was dependent on the Sec residue. Conversely, SelT gene knockdown inhibited the PACAP-induced increase in [Ca(2+)](i) and reduced hormone secretion. These findings demonstrate the implication of a selenoprotein in the regulation of Ca(2+) homeostasis and neuroendocrine secretion in response to a cAMP-stimulating trophic factor

Aux sources de l’histoire animale

Comment écrire l’histoire animale, c’est-à-dire du côté des animaux ? Cette interrogation en amène aussitôt une seconde : cette histoire animale, avec quels documents la bâtir ? L’expérience montre que la question des sources et de leur traitement est l’obstacle premier à une approche animale, l’aspect qui, avec le croisement disciplinaire, intimide le plus les chercheurs volontaires. Cette affaire forme déjà barrage pour les disciplines aux documents imposés, contraints, restreints comme l’archéozoologie, la génétique historique, l’histoire, la littérature qui, souvent, sont obligées d’adapter leur démarche à ce qui reste. Mais, même les disciplines comme l’ethnologie ou la sociologie, qui construisent d’abord leur problématique, leur épistémologie pour choisir ensuite leurs sources parmi les multiples possibles, butent sur l’« avec quoi ? » et le « comment faire ? » parce qu’elles n’en ont pas l’habitude. Que le lecteur soit rassuré : ce livre n’est pas un fastidieux répertoire de sources, mais un traité pratique des méthodes à employer, de façon à réfléchir à l’« avec quoi ? », à montrer et à suggérer des pistes et des manières de faire, à encourager les initiatives, tout en donnant l’occasion de penser concrètement les programmes, les problématiques, les épistémologies. Parce que l’histoire animale est entendue non comme une discipline mais comme un dynamisme dans le temps et l’espace, d’hier et d’aujourd’hui, ce livre s’adresse aux archéologues et aux historiens, tout autant qu’aux géographes, aux littéraires, aux ethnologues, aux sociologues, aux philosophes, ou encore aux paléogénéticiens, aux éthologues et aux vétérinaires. Et aux passionnés d’animaux

POPSEC : molecular bases of acclimation to water deficit in poplar

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