General interaction mode of CIDE:CIDE complex revealed by a mutation study of the Drep2 CIDE domain

AbstractThe CIDE domain is a well known protein–protein interaction module that is initially detected at the apoptotic DNA fragmentation factor (DFF40/45). The interaction mechanism via the CIDE domain is not well understood. To elucidate CIDE domain mediated interactions in the apoptotic DNA fragmentation system, we conducted biochemical and mutational studies and found that the surface of CIDE domains can be divided into an acidic side and a basic side. In addition, a mutagenesis study revealed that the basic surface side of Drep2 CIDE is involved in the interaction with the acidic surface side of Drep1 CIDE and Drep3 CIDE. Our research supports the idea that a charge–charge interaction might be the general interaction mode of the CIDE:CIDE interaction.Structured summary of protein interactionsDrep2andDrep2bindbymolecular sieving(View Interaction:1,2)Drep1andDrep2bindbymolecular sieving(View interaction)Drep3andDrep2bindbymolecular sieving(View interaction)Drep2andDrep3bindbyblue native page(View interaction)Drep2andDrep1bindbyblue native page(View interaction

Putative cell adhesion membrane protein Vstm5 regulates neuronal morphology and migration in the central nervous system

During brain development, dynamic changes in neuronal membranes perform critical roles in neuronal morphogenesis and migration to create functional neural circuits. Among the proteins that induce membrane dynamics, cell adhesion molecules are important in neuronal membrane plasticity. Here, we report that V-set and transmembrane domain-containing protein 5 (Vstm5), a cell-adhesion-like molecule belonging to the Ig superfamily, was found in mouse brain. Knock-down of Vstm5 in cultured hippocampal neurons markedly reduced the complexity of dendritic structures, as well as the number of dendritic filopodia. Vstm5 also regulates neuronal morphology by promoting dendritic protrusions that later develop into dendritic spines. Using electroporationin utero, we found that Vstm5 overexpression delayed neuronal migration and induced multiple branches in leading processes during corticogenesis. These results indicate that Vstm5 is a new cell-adhesion-like molecule and is critically involved in synaptogenesis and corticogenesis by promoting neuronal membrane dynamics.SIGNIFICANCE STATEMENTNeuronal migration and morphogenesis play critical roles in brain development and function. In this study, we demonstrate for the first time that V-set and transmembrane domain-containing protein 5 (Vstm5), a putative cell adhesion membrane protein, modulates both the position and complexity of central neurons by altering their membrane morphology and dynamics. Vstm5 is also one of the target genes responsible for variations in patient responses to treatments for major depressive disorder. Our results provide the first evidence that Vstm5 is a novel factor involved in the modulation of the neuronal membrane and a critical element in normal neural circuit formation during mammalian brain development.</jats:p

Motif Dynamics in Signed Directional Complex Networks

Complex networks evolve and vary their structure as time goes by. In particular, the links in those networks have both a sign and a directionality. To understand their structural principles, we measure the network motifs, which are patterns that appear much more than one would expect in randomized networks, considering both link properties. We propose motif dynamics, which is a study to investigate the change in the number of motifs, and applied the motif dynamics to an open evolving network model and empirical data. We confirm that a non-cyclic motif has a greater correlation with the system size than a cyclic structural motif. Furthermore, the motif dynamics can give us insight into the friendship between freshmen in a university

Effects of mutation at a conserved N-glycosylation site in the bovine retinal cyclic nucleotide-gated ion channel

AbstractBovine retinal cyclic nucleotide-gated (CNG) ion channel contains an evolutionary conserved N-glycosylation site in the external loop between the fifth transmembrane segment and the pore-forming region. The effect of tunicamycin treatment and the site-specific mutation suggested that the channel is glycosylated when expressed in Xenopus oocytes. To test the role of glycosylation in this channel, N-glycosylation was abolished by mutation, and the detailed permeation and the gating characteristics of the mutant channel were investigated. The charge contribution turned out to be detectable, although the mutation of the N-glycosylation site did not affect expression and functionality of the CNG channel in oocytes

Human Neural Stem Cells Genetically Modified to Overexpress Akt1 Provide Neuroprotection and Functional Improvement in Mouse Stroke Model

In a previous study, we have shown that human neural stem cells (hNSCs) transplanted in brain of mouse intracerebral hemorrhage (ICH) stroke model selectively migrate to the ICH lesion and induce behavioral recovery. However, low survival rate of grafted hNSCs in the brain precludes long-term therapeutic effect. We hypothesized that hNSCs overexpressing Akt1 transplanted into the lesion site could provide long-term improved survival of hNSCs, and behavioral recovery in mouse ICH model. F3 hNSC was genetically modified with a mouse Akt1 gene using a retroviral vector. F3 hNSCs expressing Akt1 were found to be highly resistant to H2O2-induced cytotoxicity in vitro. Following transplantation in ICH mouse brain, F3.Akt1 hNSCs induced behavioral improvement and significantly increased cell survival (50–100% increase) at 2 and 8 weeks post-transplantation as compared to parental F3 hNSCs. Brain transplantation of hNSCs overexpressing Akt1 in ICH animals provided functional recovery, and survival and differentiation of grafted hNSCs. These results indicate that the F3.Akt1 human NSCs should be a great value as a cellular source for the cellular therapy in animal models of human neurological disorders including ICH

Self-care use patterns in the UK, US, Australia, and Japan: a multinational web-based survey

AbstractBackgroundThe trend toward patient- or consumer-centered healthcare has been accelerated by advances in technology, consumer empowerment, and a shift from infectious to chronic diseases. The purpose of this study was to examine the growing self-care market by analyzing self-care patterns.MethodsWe conducted a cross-sectional, web-based survey involving adults from nine major cities in the UK, the USA, Australia, and Japan. This study examined the extent and frequency of self-care, self-care expenditure, sources of self-care information, and reasons for self-care in each country.ResultsThe results showed that the prevalence of self-care was highest in Japan (54.9%), followed by the UK (43.1%), the USA (42.5%), and Australia (40.4%). The primary reason for practicing self-care was “to manage my healthcare myself” (cited by 45.7%, 59.5%, 49.2%, and 4.1% of participants in Australia, Japan, the UK, and the USA, respectively). Significant linear associations were observed between age and the prevalence of self-care in all countries (p<0.05), indicating that self-care prevalence decreased with age in the UK, the USA, and Australia, and increased with age in Japan. The frequency with which self-care was practiced was positively correlated with age in the USA (p<0.05), Australia (p<0.01), and Japan (p<0.05). In addition to acquaintances, internet search engines and information obtained from pharmacies were considered reliable and widely used sources of self-care information.ConclusionWhen developing self-care products or services, healthcare providers and policymakers should consider self-care patterns