Visible light-driven dye-sensitized photocatalytic hydrogen production by porphyrin and its cyclic dimer and trimer: effect of multi-pyridyl-anchoring groups on photocatalytic activity and stability

The monomer, dimer, and trimer of 5,15-diphenyl-10,20-di(pyridin-4-yl)porphyrin are used to investigate the multianchoring effect on TiO2 for visible light-driven photocatalytic hydrogen production in a water medium. Further, the porphyrin trimer is prepared and analyzed by nuclear magnetic resonance (NMR) spectroscopy, absorption spectroscopy, electrochemical voltammetry, fast atom bombardment (FAB) mass spectroscopy, and density functional theory (DFT) computation. The results of this study indicate that the peak intensities of the absorption spectra increase as the number of porphyrin units increases, while changes could be barely observed in the highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) gaps. The porphyrin dimer in a 1 wt % Pt-loaded TiO2 powder photocatalyst system exhibited optimal hydrogen production performance in a stable state over a period of 80 h and at a superior rate of 1023 μmol·g–1·h–1. Further, the stability of the photocatalytic system was systematically investigated using films containing dyes on 1 wt % Pt-loaded TiO2/FTO. For a film containing the dimer, almost no change was observed in the hydrogen-bond coordination mode of the dimer and the photocurrent during the photocatalytic reaction. However, the photocurrents of the monomer and trimer were altered during visible light irradiation without altering the coordination mode, indicating that the arrangements and orientations of the porphyrins on TiO2 surfaces were altered. These results indicate that the presence of multiple anchoring groups enhance the stability of the photocatalytic system and the rate of hydrogen production

An image cytometric technique is a concise method to detect adenoviruses and host cell proteins and to monitor the infection and cellular responses induced

BackgroundGenetically modified adenoviruses (Ad) with preferential replications in tumor cells have been examined for a possible clinical applicability as an anti-cancer agent. A simple method to detect viral and cellular proteins is valuable to monitor the viral infections and to predict the Ad-mediated cytotoxicity.MethodsWe used type 5 Ad in which the expression of E1A gene was activated by 5′-regulatory sequences of genes that were augmented in the expression in human tumors. The Ad were further modified to have the fiber-knob region replaced with that derived from type 35 Ad. We infected human mesothelioma cells with the fiber-replaced Ad, and sequentially examined cytotoxic processes together with an expression level of the viral E1A, hexon, and cellular cleaved caspase-3 with image cytometric and Western blot analyses.ResultsThe replication-competent Ad produced cytotoxicity on mesothelioma cells. The infected cells expressed E1A and hexon 24 h after the infection and then showed cleavage of caspase-3, all of which were detected with image cytometry and Western blot analysis. Image cytometry furthermore demonstrated that increased Ad doses did not enhance an expression level of E1A and hexon in an individual cell and that caspase-3-cleaved cells were found more frequently in hexon-positive cells than in E1A-positive cells. Image cytometry thus detected these molecular changes in a sensitive manner and at a single cell level. We also showed that an image cytometric technique detected expression changes of other host cell proteins, cyclin-E and phosphorylated histone H3 at a single cell level.ConclusionsImage cytometry is a concise procedure to detect expression changes of Ad and host cell proteins at a single cell level, and is useful to analyze molecular events after the infection

CA-ARBAC: privacy preserving using context-aware role-based access control on Android permission system

Existing mobile platforms are based on manual way of granting and revoking permissions to applications. Once the user grants a given permission to an application, the application can use it without limit, unless the user manually revokes the permission. This has become the reason for many privacy problems because of the fact that a permission that is harmless at some occasion may be very dangerous at another condition. One of the promising solutions for this problem is context-aware access control at permission level that allows dynamic granting and denying of permissions based on some predefined context. However, dealing with policy configuration at permission level becomes very complex for the user as the number of policies to configure will become very large. For instance, if there are A applications, P permissions, and C contexts, the user may have to deal with A × P × C number of policy configurations. Therefore, we propose a context-aware role-based access control model that can provide dynamic permission granting and revoking while keeping the number of policies as small as possible. Although our model can be used for all mobile platforms, we use Android platform to demonstrate our system. In our model, Android applications are assigned roles where roles contain a set of permissions and contexts are associated with permissions. Permissions are activated and deactivated for the containing role based on the associated contexts. Our approach is unique in that our system associates contexts with permissions as opposed to existing similar works that associate contexts with roles. As a proof of concept, we have developed a prototype application called context-aware Android role-based access control. We have also performed various tests using our application, and the result shows that our model is working as desired

Metformin produces growth inhibitory effects in combination with nutlin-3a on malignant mesothelioma through a cross-talk between mTOR and p53 pathways

BackgroundMesothelioma is resistant to conventional treatments and is often defective in p53 pathways. We then examined anti-tumor effects of metformin, an agent for type 2 diabetes, and combinatory effects of metformin and nutlin-3a, an inhibitor for ubiquitin-mediated p53 degradation, on human mesothelioma.MethodsWe examined the effects with a colorimetric assay and cell cycle analyses, and investigated molecular events in cells treated with metformin and/or nutlin-3a with Western blot analyses. An involvement of p53 was tested with siRNA for p53.ResultsMetformin suppressed cell growth of 9 kinds of mesothelioma including immortalized cells of mesothelium origin irrespective of the p53 functional status, whereas susceptibility to nutlin-3a was partly dependent on the p53 genotype. We investigated combinatory effects of metformin and nutlin-3a on, nutlin-3a sensitive MSTO-211H and NCI-H28 cells and insensitive EHMES-10 cells, all of which had the wild-type p53 gene. Knockdown of p53 expression with the siRNA demonstrated that susceptibility of MSTO-211H and NCI-H28 cells to nutlin-3a was p53-dependent, whereas that of EHMES-10 cells was not. Nevertheless, all the cells treated with both agents produced additive or synergistic growth inhibitory effects. Cell cycle analyses also showed that the combination increased sub-G1 fractions greater than metformin or nutlin-3a alone in MSTO-211H and EHMES-10 cells. Western blot analyses showed that metformin inhibited downstream pathways of the mammalian target of rapamycin (mTOR) but did not activate the p53 pathways, whereas nutlin-3a phosphorylated p53 and suppressed mTOR pathways. Cleaved caspase-3 and conversion of LC3A/B were also detected but it was dependent on cells and treatments. The combination of both agents in MSTO-211H cells rather suppressed the p53 pathways that were activated by nutrin-3a treatments, whereas the combination rather augmented the p53 actions in NCI-H28 and EHMES-10 cells.ConclusionThese data collectively indicated a possible interactions between mTOR and p53 pathways, and the combinatory effects were attributable to differential mechanisms induced by a cross-talk between the pathways

In-hospital Outcome in Octogenarians with Acute Coronary Syndrome Undergoing Emergent Coronary Angiography

金沢大学附属病院臨床試験管理センターVery elderly patients have higher mortality rates than younger patients after acute coronary syndrome (ACS). However, the mechanism by which increasing age contributes to such mortality remains unclear. In addition, the efficacy and safety of invasive coronary procedures for octogenarians with ACS have not been well established. We compared the clinical characteristics and in-hospital outcome of 193 octogenarians (mean age, 83 years) with those of 1,462 younger patients (mean age, 64 years) with ACS who underwent emergent coronary angiography. Octogenarians included a greater number of females, had higher rates of cerebrovascular disease and multivessel disease, a higher Killip class, a higher Forrester class, and lower rates of smoking, diabetes, and hypercholesterolemia than the younger subjects. Interventions, including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG), were performed less frequently in octogenarians than in younger patients (88.0% versus 90.8%). The procedural success rate in octogenarians did not differ from that in younger patients. However, the in-hospital mortality rate for the octogenarians was about three times higher than for the younger patients (19.2% versus 6.9%). Multivariate analysis revealed that the predictors of in-hospital mortality in the octogenarians were a higher Killip class and a higher Forrester class. Octogenarians with ACS had fewer coronary risk factors and a similar success rate for the intervention, but had more greatly impaired hemodynamics and higher in-hospital mortality than the younger patients. Therefore, impaired myocardial reserve may contribute to a large portion of in-hospital deaths in octogenarians with ACS

Extreme deformability of insect cell membranes is governed by phospholipid scrambling

昆虫の細胞は柔らかい！ --細胞膜を柔らかくするタンパク質を発見--. 京都大学プレスリリース. 2021-06-09.Organization of dynamic cellular structure is crucial for a variety of cellular functions. In this study, we report that Drosophila and Aedes have highly elastic cell membranes with extremely low membrane tension and high resistance to mechanical stress. In contrast to other eukaryotic cells, phospholipids are symmetrically distributed between the bilayer leaflets of the insect plasma membrane, where phospholipid scramblase (XKR) that disrupts the lipid asymmetry is constitutively active. We also demonstrate that XKR-facilitated phospholipid scrambling promotes the deformability of cell membranes by regulating both actin cortex dynamics and mechanical properties of the phospholipid bilayer. Moreover, XKR-mediated construction of elastic cell membranes is essential for hemocyte circulation in the Drosophila cardiovascular system. Deformation of mammalian cells is also enhanced by the expression of Aedes XKR, and thus phospholipid scrambling may contribute to formation of highly deformable cell membranes in a variety of living eukaryotic cells

Cytotoxicity of replication-competent adenoviruses powered by an exogenous regulatory region is not linearly correlated with the viral infectivity/gene expression or with the E1A-activating ability but is associated with the p53 genotypes

BackgroundReplication-competent adenoviruses (Ad) produced cytotoxic effects on infected tumors and have been examined for the clinical applicability. A biomarkers to predict the cytotoxicity is valuable in a clinical setting.MethodsWe constructed type 5 Ad (Ad5) of which the expression of E1A gene was activated by a 5′ regulatory sequences of survivin, midkine or cyclooxygenase-2, which were highly expressed in human tumors. We also produced the same replication-competent Ad of which the fiber-knob region was replaced by that of Ad35 (AdF35). The cytotoxicity was examined by a colorimetric assay with human tumor cell lines, 4 kinds of pancreatic, 9 esophageal carcinoma and 5 mesothelioma. Ad infectivity and Ad-mediated gene expression were examined with replication-incompetent Ad5 and AdF35 which expressed the green fluorescence protein gene. Expression of cellular receptors for Ad5 and AdF35 was also examined with flow cytometry. A transcriptional activity of the regulatory sequences was investigated with a luciferase assay in the tumor cells. We then investigated a possible correlation between Ad-mediated cytotoxicity and the infectivity/gene expression, the transcriptional activity or the p53 genotype.ResultsWe found that the cytotoxicity was greater with AdF35 than with Ad5 vectors, but was not correlated with the Ad infectivity/gene expression irrespective of the fiber-knob region or the E1A-activating transcriptional activity. In contrast, replication-competent Ad produced greater cytotoxicity in p53 mutated than in wild-type esophageal carcinoma cells, suggesting a possible association between the cytotoxicity and the p53 genotype.ConclusionsSensitivity to Ad-mediated cytotoxic activity was linked with the p53 genotype but was not lineally correlated with the infectivity/gene expression or the E1A expression

Transition from Positive to Neutral in Mutation Fixation along with Continuing Rising Fitness in Thermal Adaptive Evolution

It remains to be determined experimentally whether increasing fitness is related to positive selection, while stationary fitness is related to neutral evolution. Long-term laboratory evolution in Escherichia coli was performed under conditions of thermal stress under defined laboratory conditions. The complete cell growth data showed common continuous fitness recovery to every 2°C or 4°C stepwise temperature upshift, finally resulting in an evolved E. coli strain with an improved upper temperature limit as high as 45.9°C after 523 days of serial transfer, equivalent to 7,560 generations, in minimal medium. Two-phase fitness dynamics, a rapid growth recovery phase followed by a gradual increasing growth phase, was clearly observed at diverse temperatures throughout the entire evolutionary process. Whole-genome sequence analysis revealed the transition from positive to neutral in mutation fixation, accompanied with a considerable escalation of spontaneous substitution rate in the late fitness recovery phase. It suggested that continually increasing fitness not always resulted in the reduction of genetic diversity due to the sequential takeovers by fit mutants, but caused the accumulation of a considerable number of mutations that facilitated the neutral evolution