Teaching Story without Struggle: Using Graded Readers and Their Audio Packs in the EFL Classroom

In recent years the support for extensive reading (ER) in English as a second or foreign language (ESL/EFL) programs has been compelling. When practicing extensive reading, the learner reads a wide variety of texts for pleasure and achieves a general understanding of the content while deciphering unknown words through context. This approach contrasts with intensive reading, a more traditional approach based on a slow, careful reading of a text, with goals of complete comprehension and the identification of specific details and information

TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood

After invading red blood cells (RBCs), Plasmodium falciparum (Pf) can export its own proteins to the host membrane and activate endogenous channels that are present in the membrane of RBCs. This transport pathway involves the Voltage Dependent Anion Channel (VDAC). Moreover, ligands of the VDAC partner TranSlocator PrOtein (TSPO) were demonstrated to inhibit the growth of the parasite. We studied the expression of TSPO and VDAC isoforms in late erythroid precursors, examined the presence of these proteins in membranes of non-infected and infected human RBCs, and evaluated the efficiency of TSPO ligands in inhibiting plasmodium growth, transporting the haem analogue Zn-protoporphyrin-IX (ZnPPIX) and enhancing the accumulation of reactive oxygen species (ROS). TSPO and VDAC isoforms are differentially expressed on erythroid cells in late differentiation states. TSPO2 and VDAC are present in the membranes of mature RBCs in a unique protein complex that changes the affinity of TSPO ligands after Pf infection. TSPO ligands dose-dependently inhibited parasite growth, and this inhibition was correlated to ZnPPIX uptake and ROS accumulation in the infected RBCs. Our results demonstrate that TSPO ligands can induce Pf death by increasing the uptake of porphyrins through a TSPO2-VDAC complex, which leads to an accumulation of ROS

Fish & Ships

Les poissons et leurs dérivés sont durant l’Antiquité une des bases de l’alimentation en Méditerranée. Pour autant, l’état de nos connaissances sur ces produits souffre aujourd’hui encore de nombreuses lacunes, que cet ouvrage tente partiellement de combler. Pour cela, il était nécessaire de réunir des études de spécialistes de différents horizons, d’une part pour faire le point sur des zones qui désormais sont les vitrines de nos disciplines - l’Afrique et la péninsule Ibérique notamment -, et d’autre part pour mettre l’accent sur des aires géographiques ou des périodes qui sont encore trop peu connues ou étudiées. Cet ouvrage, articulé autour de trois thèmes respectivement dédiés à des approches historiographiques et technologiques, à des études archéologiques sur l’Afrique et, enfin, à d’autres consacrées au reste de la Méditerranée, est majoritairement composé d’articles écrits par de jeunes chercheurs dont les travaux récents constituent un apport documentaire fondamental pour le renouvellement des problématiques qui sont à l’origine de la rencontre publiée ici. En ce sens, ce volume marque une étape dans l’avancée de nos connaissances en ce domaine

Asymmetric expression of transcripts derived from the shared promoter between the divergently orientated aCACA and tADA2L genes

The mammalian gene (ACACA) encoding acetyl-CoA carboxylase-α, a key regulatory enzyme of fatty acid synthesis, is transcribed from multiple promoters. We have delineated the 5′ boundary of ACACA in four species (human, mouse, rat, and ovine). The 5′ end of ACACA is located within a 600- to 700-bp CpG island encompassing a bidirectional promoter shared with the divergently oriented TADA2L, which encodes a component of chromatin-modifying complexes. In mouse and rat, this promoter, now referred to as Acaca PI, is located 43 kb upstream of the previously known regulatory regions. The shared promoter coregulates transcripts for TADA2L and ACACA in an asymmetric fashion in human and mouse tissues. A higher concentration of RNA polymerase II (Pol II) within the intergenic region in brain compared to liver of mouse reflects the greater abundance of the two transcripts in brain. The concentration of Pol II tracking downstream, which is lower than at the promoter, is not significantly different in either gene in the two tissues and does not reflect the 10- and >200-fold greater abundance of Tada2l and Acaca PI transcripts, respectively, in brain. Thus, regulation of clearance of Pol II from the promoter and the rate of elongation may therefore be determinants of the asymmetric expression of these transcripts

Improving the photophysical properties of copper(I) bis(phenanthroline) complexes

Homoleptic copper(I) bis(2,9-dialkyl-1,10-phenanthroline) units, as well as a range of related heteroleptic species, represent popular choices for building blocks in the construction of supramolecular edifices and photo- and electroactive devices. The photophysical properties of these traditionally underperforming luminescent complexes can be dramatically modified in a qualitatively predictable fashion through ligand design, the use of bichromophoric ligands, and by reconstitution of the primary coordination sphere. An overview of key excited-state processes established in these complexes is presented, with particular emphasis on recent developments and insights, as well as ramifications for developing successful strategies to prolong luminescence lifetimes and increase quantum yields

TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood

International audienceAfter invading red blood cells (RBCs), Plasmodium falciparum (Pf) can export its own proteins to the host membrane and activate endogenous channels that are present in the membrane of RBCs. This transport pathway involves the Voltage Dependent Anion Channel (VDAC). Moreover, ligands of the VDAC partner TranSlocator PrOtein (TSPO) were demonstrated to inhibit the growth of the parasite. We studied the expression of TSPO and VDAC isoforms in late erythroid precursors, examined the presence of these proteins in membranes of non-infected and infected human RBCs, and evaluated the efficiency of TSPO ligands in inhibiting plasmodium growth, transporting the haem analogue Zn-protoporphyrin-IX (ZnPPIX) and enhancing the accumulation of reactive oxygen species (ROS). TSPO and VDAC isoforms are differentially expressed on erythroid cells in late differentiation states. TSPO2 and VDAC are present in the membranes of mature RBCs in a unique protein complex that changes the affinity of TSPO ligands after Pf infection. TSPO ligands dose-dependently inhibited parasite growth, and this inhibition was correlated to ZnPPIX uptake and ROS accumulation in the infected RBCs. Our results demonstrate that TSPO ligands can induce Pf death by increasing the uptake of porphyrins through a TSPO2–VDAC complex, which leads to an accumulation of ROS

L’ESPRESSIONE DI CBFA2T3-GLIS2 ALTERA IL PROCESSO DI DIFFERENZAZIONE EMATOPOIETICA NEL MODELLO DI INDUCED PLURIPOTENT STEM CELLS (IPSC) DI LEUCEMIA ACUTA MEGACARIOBLASTICA PEDIATRICA

INTRODUZIONE: CBFA2T3-GLIS2 è un gene di fusione presente nel 15-25% delle AMKL. L’obiettivo di questo studio è stato quello di caratterizzare l’effetto di CBFA2T3-GLIS2 nel processo di differenzazione ematopoietica in un modello di iPSC e studiare l’effetto del GANT61, inibitore specifico di HH, in questo modello cellulare. METODI E RISULTATI: Le iPSC derivate da donatore sano sono state ingegnerizzate per esprimere CBFA2T3-GLIS2 sotto il controllo del promotore CD43, sfruttando il locus AAVS1 (Figura 1A). Tre colonie indipendenti di iPSC con corretta integrazione del trascritto sono state indotte a differenziare in progenitori ematopoietici e megacariociti, in cui è stata confermata l’espressione di CBFA2T3-GLIS2 e di alcuni suoi target specifici. L’analisi immunofenotipica del processo di differenzazione ematopoietica ha dimostrato che la presenza della fusione induce un aumento del numero di cellule CD43+, composte da una sottopopolazione anomala di megacariociti caratterizzata da bassi livelli di espressione dei marcatori CD41,CD42 e CD61, mai riscontrata nelle cellule di controllo (Figura 1B). Ulteriori studi hanno dimostrato che CBFA2T3-GLIS2 è sufficiente per incrementare la proliferazione cellulare (Figura 1C) e bloccare la differenzazione in megacariociti. Il trattamento dei progenitori ematopoietici derivati dalla differenzazione delle iPSC con GANT61 ha dimostrato che il farmaco già a basse concentrazioni inibisce in modo specifico l’attività proliferativa aberrante indotta da CBFA2T3-GLIS2 (Figura 1D). CONCLUSIONI: L’espressione di CBFA2T3-GLIS2 nelle iPSC riproduce le caratteristiche cellulari e molecolari delle AMKL incrementando l’espressione di geni target, inducendo la differenzazione anomala dei megacariociti e attivando la proliferazione cellulare. PROSPETTIVE FUTURE: Questo modello sarà utile per approfondire gli effetti biologici del GANT61 che ad oggi sono molto promettenti

MODELLO DI “INDUCED PLURIPOTENT STEM CELLS” (IPSC) DERIVATE DA DONATORE SANO CON IL GENE DI FUSIONE CBFA2T3-GLIS2

INTRODUZIONE: CBFA2T3-GLIS2 è un gene di fusione presente nel 15-25% delle AMKL. L’obiettivo di questo studio è stato quello di ingegnerizzare delle iPSC con CBFA2T3-GLIS2. METODI E RISULTATI: Per ingegnerizzare le iPSC da donatore abbiamo sfruttato il locus AAVS. Il locus AAV, usato generalmente per l’integrazione dall’adenovirus codifica per il gene PPP1R12C e la sua distruzione non associa con alcuna patologia conosciuta.Il gene di fusione è stato clonato nel vettore AAVS1 SA-2A-puro-pA donor. Per riprodurre un modello altamente fedele siamo andati a verificare l’espressione di CBFA2T3 nelle iPSC. I risultati hanno dimostrato che il gene non era espresso nelle iPSC (Figura 1A), quindi abbiamo inserito il gene di fusione marcato con GFP sotto il controllo di un promotore ematopoietico, il CD43. Le iPSC sono state quindi ingegnerizzate con questo vettore attraverso ricombinazione omologa “ZingFinger” mediata (Figura 1B). Dopo elettroporazione le iPSC sono state selezionate con Puromicina. Su 24 colonie resistenti all’antibiotico, 23 avevano integrato CBFA2T3-GLIS2 in omozigosi e 1 in eterozigosi. 3 di queste colonie sono state amplificate e validate per le caratteristiche di pluripotenza e per l’espressione di CBFA2T3-GLIS2 nelle cellule ematopoietiche differenziate. I risultati hanno dimostrato che le iPSC ingegnerizzate avevano mantenuto le caratteristiche di pluripotenza (Figura 1C) e il gene di fusione insieme a altri geni direttamente regolati da CBFA2T3-GLIS2 come ERG erano correttamente espressi nelle cellule ematopoietiche derivate dalla differenzazione delle iPSC (Figura 1C). CONCLUSIONI: Le iPSC ingegnerizzate nel locus AAVS1 sono un modello altamente fedele e efficiente per studiare l’effetto di fusioni di interessa onco-ematologico

The translocator protein ligand XBD173 improves clinical symptoms and neuropathological markers in the SJL/J mouse model of multiple sclerosis

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