Bovine Insulin Filaments Induced by Reducing Disulfide Bonds Show a Different Morphology, Secondary Structure, and Cell Toxicity from Intact Insulin Amyloid Fibrils

AbstractAmyloid fibrils are associated with more than 20 diseases, including Alzheimer's disease and type II diabetes. Insulin is a 51-residue polypeptide hormone, with its two polypeptide chains linked by one intrachain and two interchain disulfide bonds, and has long been known to self-assemble in vitro into amyloid fibrils. We demonstrate here that bovine insulin forms flexible filaments in the presence of a reducing agent, Tris (2-carboxyethyl) phosphine. The insulin filaments, possibly formed due to partial reduction of S-S bonds in insulin molecules, differ from intact insulin fibrils in terms of their secondary structure. The insulin filaments were determined to have an antiparallel β-sheet structure, whereas the insulin fibrils have a parallel β-sheet structure. Of importance, the cell toxicity of the insulin filaments was remarkably lower than that of the insulin fibrils. This finding supports the idea that cell toxicity of amyloids correlates with their morphology. The remarkably low toxicity of the filamentous structure should shed new light on possible pharmacological approaches to the various diseases caused by amyloid fibrils

Additional kernel observer: privilege escalation attack prevention mechanism focusing on system call privilege changes

Cyberattacks, especially attacks that exploit operating system vulnerabilities, have been increasing in recent years. In particular, if administrator privileges are acquired by an attacker through a privilege escalation attack, the attacker can operate the entire system and cause serious damage. In this paper, we propose an additional kernel observer (AKO) that prevents privilege escalation attacks that exploit operating system vulnerabilities. We focus on the fact that a process privilege can be changed only by specific system calls. AKO monitors privilege information changes during system call processing. If AKO detects a privilege change after system call processing, whereby the invoked system call does not originally change the process privilege, AKO regards the change as a privilege escalation attack and applies countermeasures against it. AKO can therefore prevent privilege escalation attacks. Introducing the proposed method in advance can prevent this type of attack by changing any process privilege that was not originally changed in a system call, regardless of the vulnerability type. In this paper, we describe the design and implementation of AKO for Linux x86 64-bit. Moreover, we show that AKO can be expanded to prevent the falsification of various data in the kernel space. Then, we present an expansion example that prevents the invalidation of Security-Enhanced Linux. Finally, our evaluation results show that AKO is effective against privilege escalation attacks, while maintaining low overhead

Inclusion of gaming disorder criteria in ICD-11: A clinical perspective in favor

Data from a specialist treatment facility for Internet addiction (IA) in Japan showed that (a) the vast majority of treatment seekers are addicted to online games, (b) their symptoms are often quite severe, and (c) there is a significant demand for IA treatment. In addition, systemic obstacles to the delivery of medical services in Japan exist due to the exclusion of IA criteria from ICD-10. Consequently, the inclusion of GD criteria in ICD-11 will almost certainly increase the capacity and quality of treatment through advances in research and possible changes in national medical systems to meet treatment demand

Ni-Catalyzed Enantioselective C-Acylation of α-Substituted Lactams

A new strategy for catalytic enantioselective C-acylation to generate α-quaternary-substituted lactams is reported. Ni-catalyzed three-component coupling of lactam enolates, benzonitriles, and aryl halides produces β-imino lactams that then afford β-keto lactams by acid hydrolysis. Use of a readily available Mandyphos-type ligand and addition of LiBr enable the construction of quaternary stereocenters on α-substituted lactams to form β-keto lactams in up to 94% ee

Coupling Between B Cell Receptor and Phospholipase C-γ2 Is Essential for Mature B Cell Development

Two signaling pathways known to be essential for progression from immature to mature B cells are BAFF receptor (BAFF-R) and the B cell receptor (BCR). Here, we first show that phospholipase C (PLC)-γ2 is required for a BAFF-R–mediated survival signal. Then, we have examined the question of whether the reduced number of mature B cells in PLC-γ2−/− mice is caused by a defect in either BCR or BAFF-R signaling. We find that a PLC-γ2 SH2 mutant, which inhibits coupling between BCR and PLC-γ2, fails to restore B cell maturation, despite supporting BAFF-dependent survival. Therefore, our data suggest that the BAFF-R–mediated survival signal, provided by PLC-γ2, is not sufficient to promote B cell maturation, and that, in addition, activation of PLC-γ2 by BCR is required for B cell development

Preparation of Ba1-xLnxFeO3-δ and BaFe1-xLnxO3-δ (Ln: trivalent ion) with cubic perovskite structure and random distribution of oxide ion vacancy

Oxides with perovskite structure and random arrangement of oxide ion, such as Ba0.5Sr0.5Fe0.2Co0.8O3-δ, attract much interest as oxygen permeation material. For wide spread of oxygen permeation devices, development of new material without Co is highly desired because of high cost of Co. Recently, we reported that arrangement of oxide ion vacancy in monoclinic BaFeO2.5-δ changes from ordered to random by partial La3+ substitution for Ba2+ site, resulting in cubic perovskite structure and improvement of electrical conductivity [1, 2]. Fujishiro reported preparation of BaFe1-xInxO3-δ with cubic perovskite structure and enhancement of electrical conductivity with In substitution [3]. It is expected that material with higher property may be developed by substitution of other trivalent ion, such as lanthanoid or Y, for Ba- or Fe- site in BaFeO2.5-δ. In this work, preparation of various Ba1-xLnxFeO3-δ and BaFe1-xLnxO3-δ (Ln: trivalent ion) was examined and factors determining substitution site and crystal structure were investigated. The samples of Ba1-xLnxFeO3-δ and BaFe1-xLnxO3-δ were prepared with Pechini method. Each solution of Ba2+, Ln3+ and Fe3+ was mixed with nominal cation composition. After addition of citric acid and ethylene glycol, the solution was heated at about 450 ºC, resulting in precursor. The precursor was calcined at 700 ºC for 24 h in air, followed by 1300 ºC for 10 h in air twice. The crystal structure and lattice constants of the specimens were investigated with X-ray diffraction. The chemical state of Fe and oxygen content of the specimens were evaluated with iodometric titration. Please click Additional Files below to see the full abstract

Ni-Catalyzed Enantioselective C-Acylation of α-Substituted Lactams

A new strategy for catalytic enantioselective C-acylation to generate α-quaternary-substituted lactams is reported. Ni-catalyzed three-component coupling of lactam enolates, benzonitriles, and aryl halides produces β-imino lactams that then afford β-keto lactams by acid hydrolysis. Use of a readily available Mandyphos-type ligand and addition of LiBr enable the construction of quaternary stereocenters on α-substituted lactams to form β-keto lactams in up to 94% ee

Watershed algorithm for moving object extraction considering energy minimization by snakes

金沢大学理工研究域電子情報学系MPEG-4, which is a video coding standard, supports object-based functionalities for high efficiency coding. MPEG-7, a multimedia content description interface, handles the object data in, for example, retrieval and/or editing systems. Therefore, extraction of semantic video objects is an indispensable tool that benefits these newly developed schemes. In the present paper, we propose a technique that extracts the shape of moving objects by combining snakes and watershed algorithm. The proposed method comprises two steps. In the first step, snakes extract contours of moving objects as a result of the minimization of an energy function. In the second step, the conditional watershed algorithm extracts contours from a topographical surface including a new function term. This function term is introduced to improve the estimated contours considering boundaries of moving objects obtained by snakes. The efficiency of the proposed approach in moving object extraction is demonstrated through computer simulations. © 2007 IEEE