Neddylation, a ubiquitylation‐like post‐translational modification, is catalyzed by a cascade composed of three enzymes: E1 activating enzyme, E2 conjugating enzyme, and E3 ligase with cullins as physiological substrates. Specifically, neddylation E2 UBE2M couples with E3 RBX1 to neddylate cullins 1–4, whereas neddylation E2 UBE2F couples with E3 RBX2/SAG to neddylate cullin 5, leading to activation of CRL1‐4 (Cullin‐RING ligases 1–4) and CRL5, respectively. While over‐activation of the neddylation‐CRLs axis occurs frequently in many human cancers, how neddylation‐CRLs regulate the function of (...) immune cells, particularly Treg cells was previously unknown. To this end, we recently performed Treg selective knockout of two neddylation E2s and two E3s, individually, driven by Foxp3‐Cre, and found that while the Ube2f‐Sag E2/E3 pair plays a minimal role, if any, the Ube2m‐Rbx1 pair is essential for the maintenance of Treg functionality, since their deletion triggers robust inflammatory response with autoimmune phenotypes. Milder phenotype severity upon Treg KO of upstream Ube2m than that of downstream Rbx1 strongly suggested that Rbx1 regulates Treg function in a manner dependent and independent of neddylation. (shrink)

“Critical-Rationalist Libertarianism” (CRL) was replied to in “Libertarianism Without Argument” (the reply). Various points in that text are here given responses. Both critical rationalism and how it applies to libertarianism are elucidated and elaborated. This response will proceed by quoting the reply where relevant (virtually all of it) and then responding immediately after the quotations, following the order of the reply’s very brief “critique” (605 words).

We present here some Boolean connexive logics (BCLs) that are intended to be connexive counterparts of selected Epstein’s content relationship logics (CRLs). The main motivation for analyzing such logics is to explain the notion of connexivity by means of the notion of content relationship. The article consists of two parts. In the first one, we focus on the syntactic analysis by means of axiomatic systems. The starting point for our syntactic considerations will be the smallest BCL and the smallest CRL. (...) In the first part, we also identify axioms of Epstein’s logics that, together with the connexive principles, lead to contradiction. Moreover, we present some principles that will be equivalent to the connexive theses, but not to the content connexive theses we will propose. In the second part, we focus on the semantic analysis provided by relating- and set-assignment models. We define sound and complete relating semantics for all tested systems. We also indicate alternative relating models for the smallest BCL, which are not alternative models of the connexive counterparts of the considered CRLs. We provide a set-assignment semantics for some BCLs, giving thus a natural formalization of the content relationship understood either as content sharing or as content inclusion. (shrink)

Axiomatizations are presented for fuzzy logics characterized by uninorms continuous on the half-open real unit interval [0,1), generalizing the continuous t-norm based approach of Hájek. Basic uninorm logic BUL is defined and completeness is established with respect to algebras with lattice reduct [0,1] whose monoid operations are uninorms continuous on [0,1). Several extensions of BUL are also introduced. In particular, Cross ratio logic CRL, is shown to be complete with respect to one special uninorm. A Gentzen-style hypersequent calculus is provided (...) for CRL and used to establish co-NP completeness results for these logics. (shrink)

Deciphering how DCAFs (DDB1‐CUL4 Associated Factors) modulate a broad spectrum of cellular processes, including cell cycle progression and maintenance of genomic integrity is critical to better understand cellular homeostasis and diseases. Cells contain more than 100 DCAFs that associate with the Cullin‐Ring Ubiquitin Ligase 4 (CRL4) complex that target specific protein substrates for degradation. DCAFs are thought to act as substrate receptors that dictate the specificity of the ubiquitination machinery (“catalytic DCAFs”). However, recent studies have suggested that some DCAFs might (...) play a different role by targeting CRL4 complexes to distinct cellular compartments (“structural DCAFs”). Once localized to their correct cellular domains, these CRLs dissociate from the structural DCAFs prior to their association with other, substrate‐specific catalytic DCAFs. Thus, we propose that DCAF switches can provide a mechanistic basis for the degradation of proteins that regulate cell growth and proliferation at precise points in space and time. (shrink)

We define process algebras with a generalised operation ∑ for choice. For every infinite cardinal κ, we prove that the algebra of transition trees with branching degree <κ is free in the class of process algebras in which ∑ is defined for all subsets with a cardinality <κ. We explain how the expressions of a fragment of the specification language μCRL may be used to denote elements of our process algebras. In particular, we explain how choice quantifiers may be used (...) to denote infinite sums. We show that choice quantifiers can simulate both the existential and the universal quantifiers of first-order logic, while the input prefix mechanism can only simulate the universal quantifier. (shrink)

Within churches, congregational health and well-being require not only efficient church leadership, but also prudent church management. Good leadership structures influence governance and ministry tasks, and the awareness of accountability is a vital concept within organisations. It shapes the entire managerial progression influencing values, objectives and practices. This article reports on a study to establish the understanding of ministerial accountability in the New Prophetic Pentecostal churches. Findings reveal a unique understanding of leaders’ personal accountability, communal and cultural ministry practices and (...) public accountability towards the broader community. This article speaks to the normative task of the Church and creates a new reflection on ministerial accountability and ethical practices as well as implications for congregational development broadly.Contribution: This article highlights findings on how New Prophetic Pentecostal churches understand the concept of ministerial accountability with limited literature on the topic. Gaining insight into the African cultural heritage and values when examining the neo-Pentecostal perspective will enhance the understanding regarding their beliefs and principles. (shrink)

Existing studies lack comprehensive insights into the success and effectiveness of culturally responsive leadership (CRL) in higher education. To address this gap, a scoping review was conducted to provide an integrated framework of CRL and guide current and future school leaders in higher education who aspire to implement it. Initially, 47 literature sources were searched, screened, and 18 articles were selected for thematic analysis based on predefined criteria. The analysis revealed three key themes: culturally responsive school leadership in higher education, (...) the success of culturally responsive leadership, and effective practices of CRL which serve as an integrative framework. The findings underscore the importance of prioritizing culturally responsive school leadership in higher education to promote access, equity, and improvement. Furthermore, the review highlights the potential impact of embracing CRL in higher education settings and fills a gap in the existing literature by offering an integrative framework. It contributes to understanding the potential of CRL to enhance higher education institutions. The recommendations and implications discussed in the review provide valuable guidance for educational leaders seeking to implement culturally responsive practices. Overall, this review enhances our understanding of CRL in the context of higher education and emphasizes its potential benefits for educational institutions. (shrink)