13 research outputs found
Potentsiaalsete AlkBH5 inhibiitorite fragmentidel põhinev disain
No full textBackground. AlkBH5 is a mammalian demethylase responsible for removal of m6A (N6-methyladenosine) modification in RNA. Multiple studies have proven the role of AlkBH5 in several
malignancies. Downregulation of demethylase activity using small-molecule ligands has therapeutic potential. Aim. Fragment-based drug design of AlkBH5 inhibitors using different computer-aided drug design techniques. Methods. The library of new potential active compounds was designed using the Core Hopping procedure on the basis of structure analysis of the previously reported active compounds. The interaction between target and designed ligands was evaluated using molecular docking, molecular dynamics simulation, and MM-GBSA calculations. Results. Eight potentially active compounds were identified and selected for the further biological evaluation. Three of them were predicted as the most promising candidates. Conclusion. The study successfully implemented fragment-based methods of computer-aided drug design to identify potential compounds that can be active against AlkBH5
The Internal Passive and the Periphrastic Passive in Journalistic Modern Standard The Internal Passive and the Periphrastic Passive in Journalistic Modern Standard
No full textAbstract This paper aims to examine whether it might be argued that different passive structures in journalistic Arabic do not necessarily convey different semantic content, as reflected in recent research. It will be shown that it is not always possible to determine the precise intention of the author based on the passive structure, i.e. which aspect of the event he emphasizes -the process or the finished result
Dengue Virus Inhibitors as Potential Broad-Spectrum Flavivirus Inhibitors
No full textBackground. Flaviviruses spread from endemic to non-endemic areas, causing illness in millions of people worldwide. The lack of effective therapies and the rapid expansion of flaviviral infections worldwide emphasize the importance of finding effective antivirals to treat such diseases. Objectives. To find out the potential broad-spectrum flavivirus inhibitors among previously reported inhibitors of DENV2/DENV4. Methods. The cytotoxicity of compounds was tested using WST-1 assay. The compounds were tested for their ability to inhibit the infection of DENV2, ZIKV, KUNV, and TBEV, and the most active compounds were also analyzed using the replicon-based assay. Interactions of one of the identified inhibitors with possible viral targets were studied using molecular dynamics simulations. Results. Two out of eight previously reported DENV2/DENV4 inhibitors demonstrated the ability to inhibit all studied viruses at low micromolar concentrations. Compound C6 demonstrated the ability to inhibit both DENV2 and TBEV. Compounds C1 (lycorine), C3 (mycophenolic acid), and C7 (vidarabine) were demonstrated as inhibitors of TBEV infection for the first time. Conclusions. Several compounds, previously described as inhibitors of DENV, are also able to inhibit other flaviviruses. This work is the first report on the anti-TBEV activity of lycorine (C1) and mycophenolic acid (C3), as well as vidarabine (C7). In addition, this is the first experimental confirmation of the antiviral activity of compound C5 and the lack of detectable antiviral activity of compound C8, demonstrating the necessity of experimental verification of the computational predictions
The language, literary works and liturgy of the pope's jews in southern France
No full textInternational audienceThe author retraces the originality of the cultural and religious universe of the “Pope’s Jews” of Southern France, living in the ‘four communities’ (arba kehilot) set up in the Venaissin County (Avignon, Carpentras, Cavaillon and l’Isle-su-Sorgue). Special attention is given to their vernacular – the shouadit (deriving from the Hebrew yehudit), a mixture of Provencal and Hebrew –, the theatre plays written in this language, and writer Armand Lunel’s testimonies on the survival of a certain number of Judeo-Provencal phrases unto this day. The paper also focuses on the three types of literary works characteristic of the “Pope’s Jews”: in Provencal – the famous “Lamb Song” (Cansoun dou cabri) of the Passover ritual; in Provencal and Hebrew – “lis obros” or pioutim, “stuffed” poems which alternate a Hebrew and a Provencal verse; and in Hebrew – pinkassim, nishmatim and tehinot. A third and last focus is laid on liturgy, with its most important prayer rituals and synagogal chant
The language, literary works and liturgy of the pope's jews in southern France
No full textInternational audienceThe author retraces the originality of the cultural and religious universe of the “Pope’s Jews” of Southern France, living in the ‘four communities’ (arba kehilot) set up in the Venaissin County (Avignon, Carpentras, Cavaillon and l’Isle-su-Sorgue). Special attention is given to their vernacular – the shouadit (deriving from the Hebrew yehudit), a mixture of Provencal and Hebrew –, the theatre plays written in this language, and writer Armand Lunel’s testimonies on the survival of a certain number of Judeo-Provencal phrases unto this day. The paper also focuses on the three types of literary works characteristic of the “Pope’s Jews”: in Provencal – the famous “Lamb Song” (Cansoun dou cabri) of the Passover ritual; in Provencal and Hebrew – “lis obros” or pioutim, “stuffed” poems which alternate a Hebrew and a Provencal verse; and in Hebrew – pinkassim, nishmatim and tehinot. A third and last focus is laid on liturgy, with its most important prayer rituals and synagogal chant
Career Choice of Undergraduate Engineering Students
No full textAbstractChoosing engineering as a profession has traditionally not been a top priority among women. Based on the theory of planned behavior (TPB), choice is contingent upon attitudes, subjective norms, and perceived behavioral control, all of which influence behavior. Our research aimed at determining whether the frequencies of these three factors are the same or different among women and men choosing engineering careers. We examined the set of three TPB factors for 330 undergraduate engineering students majoring in information and systems engineering and computer science. We asked the students what had led them to choose a future engineering career. Analyzing each response for recurring TPB factors and sub-factors, which were identified and validated, we found that undergraduate female students who did not express the attitudes factor in their statements are influenced by the subjective norm factor more than men. At a higher resolution, women are significantly more influenced than men by other people. Our study contributes to advancing our understanding about gender-dependent career choice by exploring factors and sub-factors that expand on TPB. These factors and sub-factors can serve researchers interested in developing tools for encouraging women to choose and retain STEM careers
R. David me-Roqa Martina we-ha-Skolastiqah ha-yehudit be-Qatalunya bi-yeme R. Hasdai Qresqas
No full textSi studia qui la conoscenza della teologia e della filosofia scolastica latina presso un autore ebreo del 1400, Davide di Roccamartina, e la sua possibile connessione con il filosofo ebreo Hasdai Crescas.We study here the knowledge of theology and scholastic philosophy at a Latin author jew of 1400, David Roccamartina, and its possible connection with the jew philosopher Hasdai Crescas
Author response
No full textPrevious studies had shown that the integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals both local and trans expression Quantitative Trait Loci (eQTLs) demonstrating 2 trans eQTL 'hotspots' associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provide a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation
Sugar Synthesis from CO2 in Escherichia coli
No full textSummaryCan a heterotrophic organism be evolved to synthesize biomass from CO2 directly? So far, non-native carbon fixation in which biomass precursors are synthesized solely from CO2 has remained an elusive grand challenge. Here, we demonstrate how a combination of rational metabolic rewiring, recombinant expression, and laboratory evolution has led to the biosynthesis of sugars and other major biomass constituents by a fully functional Calvin-Benson-Bassham (CBB) cycle in E. coli. In the evolved bacteria, carbon fixation is performed via a non-native CBB cycle, while reducing power and energy are obtained by oxidizing a supplied organic compound (e.g., pyruvate). Genome sequencing reveals that mutations in flux branchpoints, connecting the non-native CBB cycle to biosynthetic pathways, are essential for this phenotype. The successful evolution of a non-native carbon fixation pathway, though not yet resulting in net carbon gain, strikingly demonstrates the capacity for rapid trophic-mode evolution of metabolism applicable to biotechnology.PaperCli
