Naturally occurring or drug-induced DNA-protein crosslinks (DPCs) interfere with key DNA transactions if not repaired in a timely manner. The unique family of DPC-specific proteases Wss1/SPRTN ...targets DPC protein moieties for degradation, including stabilized topoisomerase-1 cleavage complexes (Top1ccs). Here, we describe that the efficient DPC disassembly requires Ddi1, another conserved predicted protease in Saccharomyces cerevisiae. We found Ddi1 in a genetic screen of the tdp1 wss1 mutant defective in Top1cc processing. Ddi1 is recruited to a persistent Top1cc-like DPC lesion in an S phase-dependent manner to assist in the eviction of crosslinked protein from DNA. Loss of Ddi1 or its putative protease activity hypersensitizes cells to DPC trapping agents independently from Wss1 and 26S proteasome, implying its broader role in DPC repair. Among the potential Ddi1 targets, we found the core component of Pol II and show that its genotoxin-induced degradation is impaired in ddi1. We propose that the Ddi1 protease contributes to DPC proteolysis.
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•The Ddi1 aspartic protease assists in the processing of Top1-DNA covalent complexes•Ddi1 provides cellular resistance against a broad range of DNA-protein crosslinks•Ddi1 functions independently of 26S proteasome and the dedicated DPC protease Wss1•Genotoxin-induced turnover of the RNA polymerase II depends on Wss1 and Ddi1
Proteolysis facilitates the efficient disassembly of otherwise extremely toxic DNA-protein covalent crosslinks. Serbyn et al. show that the aspartic protease Ddi1 protects cells against a broad variety of such crosslinks and further investigate how Ddi1 coordinates with known proteolytic mechanisms involved in their elimination.
We are observing more often extreme climate incidents because of global warming. There is a dire requirement for governments, enterprises, the overall population, and academics to take facilitated ...activities so as to handle the difficulties forced by environmental change. The most important strategic issue is to design an effective and environmentally concerned logistics system as transportation is one of the fundamental reasons for carbon emanations. Having this goal and mentioned highly important contributions in the field, this article introduces an unprecedented integrated mathematical model for a green solid transportation system with dwell time to execute the carbon tax, cap, and offset regulation. Due to market fluctuations, the supply and demand parameters are not always of crisp nature. Hence, a twofold (type-2 intuitionistic) uncertainty is incorporated in this article to provide a realistic transportation system. A new ranking defuzzification technique is presented for conversion into a deterministic form. After that, a fuzzy technique and a nonfuzzy technique are used to get the Pareto-optimal solution of the proposed problem. The performances of our findings are discussed with industrial-based application examples. Moreover, a comparative study is explored among the other relevant existing techniques. Managerial insights, conclusions, and avenues of future scopes are offered at the end of this article.
Pili have been demonstrated to contribute to the pathogenicity of many bacterial pathogens. Flp pilus encoded by the tad locus belongs to the type IVb pilus. Our previous study has revealed that the ...intact tad locus is essential for Flp pilus formation in Actinobacillus pleuropneumoniae, a very important porcine respiratory pathogen. To further investigate the functions of Flp pilus in A. pleuropneumoniae pathogenesis, the flp1 and tadD single deletion mutants were constructed by homologous recombination. Both of the mutant strains lost pilus on their cell surfaces. The abilities of biofilm formation, cell adhesion, resistance to phagocytosis, survival in swine whole blood, and in vivo colonization of the two mutants were significantly reduced compared with those of the parental strain. The corresponding complemented strains recovered the phenotypes. These results demonstrated that flp1 and tadD were essential for the biosynthesis of Flp pilus and that the pilus played important roles during infection of A. pleuropneumoniae.
•The genes flp1 and tadD are essential for biosynthesis of A. pleuropneumoniae Flp pilus.•A. pleuropneumoniae Flp pilus is important for biofilm formation.•A. pleuropneumoniae Flp pilus is involved in adherence and anti-phagocytosis in vitro.•Flp pilus plays essential roles in A. pleuropneumoniae colonization in vivo.
•A comprehensive review on multi-floor facility problem (MFLP) is presented.•Different applications of MFLP across various industries are discussed.•Basic features of the problem to capture different ...situations are identified.•Formulation approaches of the problem and the resolution methods are introduced.•Several issues and research directions are highlighted for future work.
Facility layout problem is a well-known optimization problem which generally deals with the arrangement of the facilities required in an organization. This problem has received much attention during the past decades. However, the researchers have mainly focused on the case where a single floor is available. While, in the competitive world, it is clear that using multi-floor structure layouts are much more efficient and in some cases necessary due to the nature of the functions and activities performed in the firms. Hence, this issue has recently attracted much attention and is becoming increasingly popular. Nevertheless, the lack of a review study on this subject for directing the new research is a great gap that has not been regarded so far. In this paper, first a well-designed framework is presented. Then, all literature references in the field of multi-floor facility problem (MFLP) are gathered, categorized and reviewed thoroughly based on the framework. Accordingly, different applications of MFLP across various industries are discussed; basic features of the problem to capture different situations are identified; the formulation approaches to address the problems and the relevant resolution methodologies are introduced; the majority of the contributions proposed in the literature are analysed from different perspectives. Finally, several issues and research directions are highlighted to be investigated in future work.
Frustrated Lewis pairs (FLPs) composed of acidic alane and basic phosphane functions, separated by a xanthene linker, can be prepared through the corresponding Me3Sn derivative and methyl aluminum ...compounds with elimination of Me4Sn. This way MeClAl‐, Cl2Al‐ and (C6F5)2Al‐ moieties could be introduced and the resulting FLPs are stabilized by a further equivalent of the alane precursors. In contact with the FLPs CO2 is bound via the C atom at the phosphane functions and the two O atoms at the Al centers. The residues at the latter determine the binding strength. Hence, in case of MeClAl CO2 capture occurs at higher pressure and under ambient conditions CO2 is released again, while for Cl2Al and (C6F5)2Al CO2 binding becomes irreversible. The results of DFT calculations rationalize these findings by the high thermodynamic stabilization in case of more electronegative residues, which concomitantly lead to higher barriers, and in case of (C6F5)2Al further stabilization is achieved through a low reorganization energy.
Exchange of the players stannane and alane provides a viable route to intramolecular FLPs with large separations between Lewis acidic aluminum und Lewis basic phosphane functions. Neutral molecules occupy the space between the two moieties and are easily displaced by approaching substrates like CO2, which is spanned in the reaction pocket ‐ particularly strongly if the residues at the Al centers correspond to C6F5.
Site‐specific conditional inactivation technologies using Cre‐loxP or Flp‐FRT systems are becoming increasingly important for the elucidation of gene function and disease mechanism in vivo. A large ...number of gene knockout mouse models carrying complex conditional alleles have been generated by global community efforts and made available for biomedical researchers. The structures of conditional alleles in these mice are becoming increasingly complex and sophisticated, and so the validation of the genetic quality of these alleles is likewise becoming a laborious task for individual researchers. To ensure the reproducibility of conditional experiments, the researcher should confirm that loxP or FRT is integrated at the correct positions in the genome prior to start of the experiments. We report the successful design of universal PCR primers specific to loxP and FRT for the quick validation of conditional floxed and Flrted alleles. The primer set consists of forward and reverse primers complimentary to the loxP or FRT sequences with partial modifications at the 5ʹ end containing 6‐base restriction endonuclease recognition sites. The universal primer set was tested to detect genomic intervals between a pair of cis‐integrated loxP or FRT and was useful for quickly validating various floxed or Flrted alleles in conditional mice.
The universal PCR primer set specific to loxP and FRT has been developed and can be used for quickly validating various floxed or Flrted alleles in conditional mice.
This study provides a framework for identifying, designing, and validating a flipped learning pattern to enhance problem- based teaching approach in higher education instructors in teaching the ...English language. Also, this endeavors to offer a general blueprint for designing a pedagogical pattern as an improvement strategy in teaching and learning English. The present study is an applied and mixed-method research. In the qualitative phase, a systematic review of 137 written and electronic documents was performed to identify the components of the pattern. Besides, in-depth interviews with 32 available and purposeful experts were done to collect data. As a methodology, researchers used inductive qualitative content analysis. To confirm the obtained components, CVR and CVI were performed in quantitative part with 25 available experts. The final influential elements in pattern formation were determined and approved in 6 main components (selected code), 18 sub-components (pivot code), and 94 properties (open code). Based on the results of CVR = 0.9, CVI = 1, and the reliability of the questionnaire r = 0.83, all 118 components were confirmed. The activities before, during, and after the class were separately approved along with the independent activities of the teacher and learner. The results indicated the acceptability of the pattern indicators. It showed that choosing the correct and principled teaching method with conscious design can solve English teaching-learning problems according to the experts’ perspectives. Besides, it not only helps English instructors and learners how to plan but also encourages them to use it in various fields.
UNIVERSITY TRAINING AND PROFESSIONAL NEEDS FOR ALGERIAN JURISTS Charef Eddine KAOUADJI
Analele Universității din Craiova. Annales de l'Université de Craiova = Annals of the University of Craiova. Seria Psihologie, pedagogie,
06/2022, Volume:
44, Issue:
1
Journal Article
Open access
This article is part of the field of French for specific objectives (FOS) more particularly, in French as a professional language (FLP). We target a specific audience, in this case jurists working in ...several professional sectors: banks, electricity and hydrocarbons. We want through this expertise, to characterize the university training received by these jurists, which is essentially based on classical Arabic, in order to arrive at a definition of their language needs in the job market. First, we will define their exit profile by focusing on expertise in legal French programs. Then, we will analyze their entry profile into the job market by using semistructured interviews with jurists, in a second step
Recent reports of radical formation within frustrated Lewis pairs (FLPs) suggested that single‐electron transfer (SET) could play an important role in their chemistry especially for C−C coupling. In ...sharp contrast, our extensive dispersion‐corrected DFT calculations show that although reactive benzhydryl radical along with phosphine radical cation species can be kinetically generated from bulky phosphines and benzhydryl cation, direct P−C hetero‐coupling may lead to bulky phosphonium cation as reactive carbocation transfer reagents to styrene substrates, which is kinetically much more favorable than the recently proposed radical C−C coupling between benzhydryl radical and styrene. Similarly, meta‐stable radical cation Mes3P+⋅ salt is also kinetically accessible via SET reactions of Mes3P and B(C6F5)3 with 0.5 equivalent of p‐O2C6Cl4.
Extensive DFT calculations show that both radical HCAr2⋅ and carbocation HCAr2+ are thermally accessible from the bulky phosphonium Mes3P−CHAr2+, which are further kinetically favored by HCAr2⋅ radical self‐dimerization and by nucleophilic alkene trapping, respectively.
•We report the identification of flp and flp-GPCR gene homologues in parasitic nematodes.•We provide data to support re-evaluation of the number of flp-genes in nematodes.•Post BLAST phylogenetic ...analysis facilitates identification of putative flp-GPCRs in nematode parasites.•We expose the most highly conserved flp and flp-GPCR genes in key pathogens within phylum Nematoda.
FMRFamide-like peptide (FLP) receptors are appealing as putative anthelmintic targets. To date, 31 flp-encoding genes have been identified in Caenorhabditis elegans and thirteen FLP-activated G-protein coupled receptors (FLP-GPCRs) have been reported. The lack of knowledge on FLPs and FLP-GPCRs in parasites impedes their functional characterisation and chemotherapeutic exploitation. Using homology-based BLAST searches and phylogenetic analyses this study describes the identification of putative flp and flp-GPCR gene homologues in 17 nematode parasites providing the first pan-phylum genome-based overview of the FLPergic complement. These data will facilitate FLP-receptor deorphanisation efforts in the quest for novel control targets for nematode parasites.
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