Universal tools for analysing structures and interactions in geometry

This study examined symmetry and perspective in modern geometric transformations, treating them as functions that preserve specific properties while mapping one geometric figure to another. The purpose of this study was to investigate geometric transformations as a tool for analysis, to consider invariants as universal tools for studying geometry. Materials and Methods: The Erlangen ideas of F. I. Klein were used, which consider geometry as a theory of group invariants with respect to the transformation of the plane and space. Results and Discussion: Projective transformations and their extension to two-dimensional primitives were investigated. Two types of geometric correspondences, collinearity and correlation, and their properties were studied. The group of homotheties, including translations and parallel translations, and their role in the affine group were investigated. Homology with ideal line axes, such as stretching and centre stretching, was considered. Involutional homology and harmonic homology with the centre, axis, and homologous pairs of points were investigated. In this study unified geometry concepts, exploring how different geometric transformations relate and maintain properties across diverse geometric systems. Conclusions: It specifically examined Möbius transforms, including their matrix representation, trace, fixed points, and categorized them into identical transforms, nonlinear transforms, shifts, dilations, and inversions

Judaism in the Commentary of Muqâtil b. Süleymân

Çalışmamızda Mukâtil b. Süleyman'ın yazmış olduğu "Tefsîr-i Kebîr" adlı eserinde Yahudi inancı ve karakteri hakkında düşünce ve fikirlerini aktarmaya çalışılmıştır. İlk olarak Yahudilerle alakalı ayetler tespit edilmiş, sonra da konular halinde işlenmiştir. Çalışmamız sadece müfessirimizin görüşleri ile yetinmemiş, diğer müfessirler ve ara sıra Tevrat'a, konuların benzerlik ve farklılık açısından aydınlatılmıştır.Tezimiz, giriş, iki bölüm ve sonuçtan oluşmaktadır. Giriş kısmında, Mukâtil b. Süleyman'ın hayatı, eserleri ve yaşadığı döneme ait bilgiler ele alınmıştır. Birinci bölümde, Kur'an'a ve müfessirimize göre Yahudilerin inançları ele alınmıştır. İkinci bölümde ise Yahudilerin özellikleri, yani kendilerinin oluşturmuş oldukları karakterleri zikredilmeye çalışılmıştır. Sonuç kısmında da konumuzun genel bir değerlendirilmesi yapılmaya çalışılmıştır.This study investigates Jewish beliefs and character expressed in the Qur'anic commentary of Muqatil b. Sulayman, Tafsir al-Kabir. It firstly deals with Qur'anic verses on Jews. Secondly, it refers to the other Muslim commentators as well as to the Torah, so the similarities and differences can easily be discerned.It consists of an introduction, two chapters and summary. The life, works and environment of Muqatil b. Sulayman are the subjects of the introduction. Chapter One deals with Jewish beliefs according to the Qur'an and Muqatil b. Sulayman. Chapter Two tackles Jewish character and peculiarities. Summary abstracts and evaluates the consequences of the study

eIF2B as a Target for Viral Evasion of PKR-Mediated Translation Inhibition

RNA-activated protein kinase (PKR) is one of the most powerful antiviral defense factors of the mammalian host. PKR acts by phosphorylating mRNA translation initiation factor eIF2α, thereby converting it from a cofactor to an inhibitor of mRNA translation that strongly binds to initiation factor eIF2B. To sustain synthesis of their proteins, viruses are known to counteract this on the level of PKR or eIF2α or by circumventing initiation factor-dependent translation altogether. Here, we report a different PKR escape strategy executed by sandfly fever Sicilian virus (SFSV), a member of the increasingly important group of phleboviruses. We found that the nonstructural protein NSs of SFSV binds to eIF2B and protects it from inactivation by PKR-generated phospho-eIF2α. Protein synthesis is hence maintained and the virus can replicate despite ongoing full-fledged PKR signaling in the infected cells. Thus, SFSV has evolved a unique strategy to escape the powerful antiviral PKR.RNA-activated protein kinase (PKR) is a major innate immune factor that senses viral double-stranded RNA (dsRNA) and phosphorylates eukaryotic initiation factor (eIF) 2α. Phosphorylation of the α subunit converts the eIF2αβγ complex into a stoichiometric inhibitor of eukaryotic initiation factor eIF2B, thus halting mRNA translation. To escape this protein synthesis shutoff, viruses have evolved countermechanisms such as dsRNA sequestration, eIF-independent translation by an internal ribosome binding site, degradation of PKR, or dephosphorylation of PKR or of phospho-eIF2α. Here, we report that sandfly fever Sicilian phlebovirus (SFSV) confers such a resistance without interfering with PKR activation or eIF2α phosphorylation. Rather, SFSV expresses a nonstructural protein termed NSs that strongly binds to eIF2B. Although NSs still allows phospho-eIF2α binding to eIF2B, protein synthesis and virus replication are unhindered. Hence, SFSV encodes a unique PKR antagonist that acts by rendering eIF2B resistant to the inhibitory action of bound phospho-eIF2α

Structural and functional insight into how the Plasmodium falciparum VAR2CSA protein mediates binding to chondroitin sulfate A in placental malaria

Malaria is a major global health problem. Pregnant women are susceptible to infection regardless of previously acquired immunity. Placental malaria is caused by parasites capable of sequestering in the placenta. This is mediated by VAR2CSA, a parasite antigen that interacts with chondroitin sulfate A (CSA). One vaccine strategy is to block this interaction with VAR2CSA-specific antibodies. It is a priority to define a small VAR2CSA fragment that can be used in an adhesion blocking vaccine. In this, the obvious approach is to define regions of VAR2CSA involved in receptor binding. It has been shown that full-length recombinant VAR2CSA binds specifically to CSA with nanomolar affinity, and that the CSA-binding site lies in the N-terminal part of the protein. In this study we define the minimal binding region by truncating VAR2CSA and analyzing CSA binding using biosensor technology. We show that the core CSA-binding site lies within the DBL2X domain and parts of the flanking interdomain regions. This is in contrast to the idea that single domains do not possess the structural requirements for specific CSA binding. Small-angle x-ray scattering measurements enabled modeling of VAR2CSA and showed that the CSA-binding DBL2X domain is situated in the center of the structure. Mutating classic sulfate-binding sites in VAR2CSA, along with testing dependence of ionic interactions, suggest that the CSA binding is not solely dependent on the sulfated CSA structure. Based on these novel PfEMP1 structure-function studies, we have constructed a small VAR2CSA antigen that has the capacity to induce highly adhesion-blocking antibodies

Epithelial Sodium Channel-α Mediates the Protective Effect of the TNF-Derived TIP Peptide in Pneumolysin-Induced Endothelial Barrier Dysfunction

BackgroundStreptococcus pneumoniae is a major etiologic agent of bacterial pneumonia. Autolysis and antibiotic-mediated lysis of pneumococci induce release of the pore-forming toxin, pneumolysin (PLY), their major virulence factor, which is a prominent cause of acute lung injury. PLY inhibits alveolar liquid clearance and severely compromises alveolar–capillary barrier function, leading to permeability edema associated with pneumonia. As a consequence, alveolar flooding occurs, which can precipitate lethal hypoxemia by impairing gas exchange. The α subunit of the epithelial sodium channel (ENaC) is crucial for promoting Na+ reabsorption across Na+-transporting epithelia. However, it is not known if human lung microvascular endothelial cells (HL-MVEC) also express ENaC-α and whether this subunit is involved in the regulation of their barrier function.MethodsThe presence of α, β, and γ subunits of ENaC and protein phosphorylation status in HL-MVEC were assessed in western blotting. The role of ENaC-α in monolayer resistance of HL-MVEC was examined by depletion of this subunit by specific siRNA and by employing the TNF-derived TIP peptide, a specific activator that directly binds to ENaC-α.ResultsHL-MVEC express all three subunits of ENaC, as well as acid-sensing ion channel 1a (ASIC1a), which has the capacity to form hybrid non-selective cation channels with ENaC-α. Both TIP peptide, which specifically binds to ENaC-α, and the specific ASIC1a activator MitTx significantly strengthened barrier function in PLY-treated HL-MVEC. ENaC-α depletion significantly increased sensitivity to PLY-induced hyperpermeability and in addition, blunted the protective effect of both the TIP peptide and MitTx, indicating an important role for ENaC-α and for hybrid NSC channels in barrier function of HL-MVEC. TIP peptide blunted PLY-induced phosphorylation of both calmodulin-dependent kinase II (CaMKII) and of its substrate, the actin-binding protein filamin A (FLN-A), requiring the expression of both ENaC-α and ASIC1a. Since non-phosphorylated FLN-A promotes ENaC channel open probability and blunts stress fiber formation, modulation of this activity represents an attractive target for the protective actions of ENaC-α in both barrier function and liquid clearance.ConclusionOur results in cultured endothelial cells demonstrate a previously unrecognized role for ENaC-α in strengthening capillary barrier function that may apply to the human lung. Strategies aiming to activate endothelial NSC channels that contain ENaC-α should be further investigated as a novel approach to improve barrier function in the capillary endothelium during pneumonia