Rôle de la protéine FBXW4 dans le complexe SCF et dans le développement du split hand/split foot malformation de type 3 (SHFM3)

La dégradation des protéines, appelée protéolyse, est un mécanisme essentiel pour le fonctionnement et la survie cellulaire. Elle se fait en grande partie grâce à l’ubiquitination des protéines qui permet au protéasome de les reconnaître et de les cliver. Dans le cadre de ce projet, et ce, à partir de deux cas cliniques, j’ai étudié le rôle la protéine F-box/WD repeat-containing protein 4 (FBXW4) dans ce processus de dégradation. Les patients étaient tous deux atteints d’un syndrome polymalformatif caractérisé par une ectrodactylie appelé split hand/split foot malformation de type 3 (SHFM3) et par une insuffisance rénale chronique. Ils étaient aussi tous deux porteurs d’une mutation P376Q dans FBXW4. Comme on suspectait déjà que FBXW4 appartienne à un complexe d’ubiquitination, nous avons émis l’hypothèse que la mutation affectait l’assemblage de ce complexe et causait ainsi les désordres cliniques identifiés. J’ai donc reproduit cette mutation in vitro ainsi que d’autres à cette position pour en étudier les effets dans le système d’expression des ovocytes de Xenopus laevis. J’ai constaté que FBXW4 était organisé en homomères et que la nature du résidu 376 jouait un rôle dans cet assemblage. J’ai aussi observé que la nature du résidu 376 affectait aussi la liaison de FBXW4 avec Skp1, une autre protéine qui se retrouve dans le complexe. Ces travaux ont ainsi permis d’en arriver aux conclusions suivantes : 1) la mutation des patients affecte l’assemblage oligomérique de FBXW4, 2) elle est donc fort possiblement causale, et 3) elle entraînerait la maladie dû à un désordre de l’ubiquitination de certaines protéines durant le développement.Protein degradation, also known as proteolysis, is essential for cell function and survival. It is most often achieved through the ubiquitination of proteins, a process that allows the proteasome to recognize and cleave such proteins. In this project, I studied two clinical cases in which the protein F-box/WD repeat-containing protein 4 (FBXW4) was believed to play a role. Both patients suffered from a polymalformative syndrome characterized by an ectrodactyly called type 3 split hand/split foot malformation (SHFM3) and chronic renal failure. Both patients also bore a P376Q mutation in FBXW4. As previous studies was consistent with the possibility that FBXW4 was part of an ubiquitination complex, we hypothesized that the mutation affected the assembly of this complex and resulted in the observed clinical disorders. I therefore reproduced the mutation in vitro among others at this location and characterized the effects of such mutations in Xenopus laevis oocyte expression system. I found that FBXW4 was organized in homooligomers and that the nature of the residue of position 376 played a role in assembly of the FBXW4 containing complex. I also found that the nature of residue 376 affected the binding of FBXW4 to another protein in the complex, that is, to Skp1. These results allow us to draw the following conclusions: 1) the mutation identified affects the oligomeric assembly of FBXW4, 2) it is thus very likely to be causative, and 3) it could cause an ubiquitination disorder in which certain proteins are not properly degraded during developmen

Advancements and Challenges in Energy-efficient 6G Mobile Communication Network

The arrival of 6G mobile communication networks is anticipated to revolutionize the technological landscape, bringing about profound innovations. This research paper explores the various technological advancements that will pave the way for the advent of 6G networks, with a particular focus on addressing energy consumption. It is widely recognized that energy efficiency plays a crucial role in the evolution of 6G networks. To enhance network performance, user experience, and resource management, the integration of Artificial Intelligence (AI) is expected to be a pivotal technology. AI-based solutions can effectively optimize energy usage and contribute to the overall efficiency of 6G networks. Furthermore, the incorporation of wireless communication systems, telecommunication, and the Internet of Things (IoT) will be integral to the infrastructure of 6G networks. The need for significant enhancements in 6G networks is also examined in this study. Ensuring the safety and protection of 6G networks from cyber threats becomes increasingly important due to the growing reliance on networked communication and the sensitive nature of transmitted information. Cutting-edge security methods such as homomorphic encryption and blockchain technology may be essential in this regard. Moreover, this research paper explores the impact of 6G networks on various domains and discusses the challenges that must be overcome to unlock the technology’s full potential. To ensure responsible adoption and usage of 6G networks, the development of new business models and regulatory frameworks may be necessary to support their implementation while addressing energy consumption concerns

Thermophysical behavior of date palm fiber-reinforced polyvinylchloride /low-density polyethylene/acrylonitrile butadiene rubber copolymer ternary composite

Date palm tree leaf-reinforced polymer composites have important advantages, such as sustainability and lowcost. In the present study, ternary blend composites of polyvinyl chloride (PVC), low-density polyethylene (LDPE), and acrylonitrile butadiene rubber (NBR) copolymer (LDPE/PVC: C0, LDPE/PVC/NBR:C1) as well as reinforced composites with 10, 20, and 30 wt.% of alkali treated date palm fiber (TDPF) (C2, C3 and C4 respectively) were fabricated using a melt blending extrusion process. TDPF and the NBR copolymer were used to improve the interfacial bonding, compatibility, and thermo-mechanical properties of the composite, yielding the highest tensile strength of 32 MPa for the composite containing 10 wt.% TDPF. Moreover, the morphological analysis showed that the incorporation of the NBR copolymer enhanced the compatibility of the blend. Mechanical tests revealed that the hardness of the TDPF/PVC/LDPE/NBR composite increased in the order C2 (450 MPa) < C3 < C4 (540 MPa). In addition, the flexural and tensile moduli of the composite increased with increasing TDPF content, with the highest values (534 and 1585 MPa, respectively) observed for composite C4. Thermal analysis revealed increased Tonset and T10% values, indicating an improved thermal stability of the composite. This study clearly demonstrates that the (DPF/PVC/LDPE/NBR) composites can be used in various high-tech engineering applications, which require excellent properties

Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters

Potassium-coupled chloride transporters (KCCs) play crucial roles in regulating cell volume and intracellular chloride concentration. They are characteristically inhibited under isotonic conditions via phospho-regulatory sites located within the cytoplasmic termini. Decreased inhibitory phosphorylation in response to hypotonic cell swelling stimulates transport activity, and dysfunction of this regulatory process has been associated with various human diseases. Here, we present cryo-EM structures of human KCC3b and KCC1, revealing structural determinants for phosphoregulation in both N- and C-termini. We show that phosphomimetic KCC3b is arrested in an inward-facing state in which intracellular ion access is blocked by extensive contacts with the N-terminus. In another mutant with increased isotonic transport activity, KCC1D19, this interdomain interaction is absent, likely due to a unique phospho-regulatory site in the KCC1 N-terminus. Furthermore, we map additional phosphorylation sites as well as a previously unknown ATP/ADP-binding pocket in the large Cterminal domain and show enhanced thermal stabilization of other CCCs by adenine nucleotides. These findings provide fundamentally new insights into the complex regulation of KCCs and may unlock innovative strategies for drug development

Hybridité textuelle et altérité identitaire dans Zabor ou les psaumes de Kamel Daoud

After the success of his first novel Meursault contre-enquête (2013), Kamel Daoud returns with a second novel: Zabor ou les psaumes (2017). This title suggests a cross-reference with one of the Sacred Books in an intertextual relationship. This book, combined with the name of the prophet who received the revelation of the book and the author's eponym, could suggest that Kamel Daoud positions himself as a "prophet". This article attempts to read this work in the light of this horizon of expectation, paying particular attention to the various crossroads that the notion of hybridity synthesizes. This approach leads to an analysis of the otherness of identity, which is another particularity of this novel, insofar as Daoud identifies with his character, thus turning his novel into autofiction

The Evolution of Wireless Sensor Networks through Smart Radios for Energy Efficiency

This article investigates the significant influence of smart radios on the energy efficiency of Wireless Sensor Networks (WSNs). It explores the incorporation of intelligent radios as a crucial element to enhance WSNs’ sustainability, providing a novel approach to tackle energy-related challenges. Smart radios are essential for prolonging the lifespan of sensor devices and reducing the environmental effect of WSNs by autonomously adjusting communication protocols and optimizing energy consumption. This paper also highlights the differences between 5G and 6G technologies within the WSNs framework. While 5G brought improvements in data speed and connectivity, 6G represents a significant progress by prioritizing energy efficiency as a fundamental goal. This shift represents a fundamental change, with a primary focus on achieving extremely low energy consumption and ensuring the sustainable operation of WSNs. The paper examines crucial technological factors enabling 6G to outperform its predecessor, establishing it as a revolutionary force in the field of wireless communication for sensor networks. This research illuminates the crucial function performed by smart radios in connecting the desire for energy efficiency with the changing environment of wireless sensor networks

Advancements and Challenges in Energy-efficient 6G Mobile Communication Network

The arrival of 6G mobile communication networks is anticipated to revolutionize the technological landscape, bringing about profound innovations. This research paper explores the various technological advancements that will pave the way for the advent of 6G networks, with a particular focus on addressing energy consumption. It is widely recognized that energy efficiency plays a crucial role in the evolution of 6G networks. To enhance network performance, user experience, and resource management, the integration of Artificial Intelligence (AI) is expected to be a pivotal technology. AI-based solutions can effectively optimize energy usage and contribute to the overall efficiency of 6G networks. Furthermore, the incorporation of wireless communication systems, telecommunication, and the Internet of Things (IoT) will be integral to the infrastructure of 6G networks. The need for significant enhancements in 6G networks is also examined in this study. Ensuring the safety and protection of 6G networks from cyber threats becomes increasingly important due to the growing reliance on networked communication and the sensitive nature of transmitted information. Cutting-edge security methods such as homomorphic encryption and blockchain technology may be essential in this regard. Moreover, this research paper explores the impact of 6G networks on various domains and discusses the challenges that must be overcome to unlock the technology’s full potential. To ensure responsible adoption and usage of 6G networks, the development of new business models and regulatory frameworks may be necessary to support their implementation while addressing energy consumption concerns

EXISTENCE OF SOLUTIONS TO DIFFERENTIAL INCLUSIONS WITH FRACTIONAL ORDER AND IMPULSES

We establish sufficient conditions for the existence of solutions for a class of initial value problem for impulsive fractional differential inclusions involving the Caputo fractional derivative. We consider the cases when the multivalued nonlinear term takes convex values as well as nonconvex values. The topological structure of the set of solutions is also considered