Col4a3-/- Mice on Balb/C Background Have Less Severe Cardiorespiratory Phenotype and SGLT2 Over-Expression Compared to 129x1/SvJ and C57Bl/6 Backgrounds

Alport syndrome (AS) is a hereditary renal disorder with no etiological therapy. In the preclinical Col4a3^-/- model of AS, disease progression and severity vary depending on mouse strain. The sodium-glucose cotransporter 2 (SGLT2) is emerging as an attractive therapeutic target in cardiac/renal pathologies, but its application to AS remains untested. This study investigates cardiorespiratory function and SGLT2 renal expression in Col4a3^-/- mice from three different genetic backgrounds, 129x1/SvJ, C57Bl/6 and Balb/C. male Col4a3^-/- 129x1/SvJ mice displayed alterations consistent with heart failure with preserved ejection fraction (HFpEF). Female, but not male, C57Bl/6 and Balb/C Col4a3^-/- mice exhibited mild changes in systolic and diastolic function of the heart by echocardiography. Male C57Bl/6 Col4a3^-/- mice presented systolic dysfunction by invasive hemodynamic analysis. All strains except Balb/C males demonstrated alterations in respiratory function. SGLT2 expression was significantly increased in AS compared to WT mice from all strains. However, cardiorespiratory abnormalities and SGLT2 over-expression were significantly less in AS Balb/C mice compared to the other two strains. Systolic blood pressure was significantly elevated only in mutant 129x1/SvJ mice. The results provide further evidence for strain-dependent cardiorespiratory and hypertensive phenotype variations in mouse AS models, corroborated by renal SGLT2 expression, and support ongoing initiatives to develop SGLT2 inhibitors for the treatment of AS.     

Dimerization Tendency of 3CLpros of Human Coronaviruses Based on the X-ray Crystal Structure of the Catalytic Domain of SARS-CoV-2 3CLpro

3CLpro of SARS-CoV-2 is a promising target for developing anti-COVID19 agents. In order to evaluate the catalytic activity of 3CLpros according to the presence or absence of the dimerization domain, two forms had been purified and tested. Enzyme kinetic studies with a FRET method revealed that the catalytic domain alone presents enzymatic activity, despite it being approximately 8.6 times less than that in the full domain. The catalytic domain was crystallized and its X-ray crystal structure has been determined to 2.3 Å resolution. There are four protomers in the asymmetric unit. Intriguingly, they were packed as a dimer though the dimerization domain was absent. The RMSD of superimposed two catalytic domains was 0.190 for 182 Cα atoms. A part of the long hinge loop (LH-loop) from Gln189 to Asp197 was not built in the model due to its flexibility. The crystal structure indicates that the decreased proteolytic activity of the catalytic domain was due to the incomplete construction of the substrate binding part built by the LH-loop. A structural survey with other 3CLpros showed that SARS-CoV families do not have interactions between DM-loop due to the conformational difference at the last turn of helix α7 compared with others. Therefore, we can conclude that the monomeric form contains nascent enzyme activity and that its efficiency increases by dimerization. This new insight may contribute to understanding the behavior of SARS-CoV-2 3CLpro and thus be useful in developing anti-COVID-19 agents.     

Who will cross the border? – The transition of political discussion into the newly emerged venues

This study explores the political implications of new communication technologies with a focus on their role as political discussion venues. Assuming that new technologies could expand the sphere for political discourse, we investigate the transition of citizens’ face-to-face political discussion into the computer-mediated online context. With analyses of a representative sample of US adults, this study explicates the link between the traditional and newly emerged discussion venues online. Our results reveal that significant differences in the transition pattern arise from variances in citizens’ political interest and age. In addition, in an attempt to reconcile the two seemingly conflicting hypotheses, we examine the role of political interest and age in the transition process within one integrated theoretical framework. Our findings highlight the conditions under which the democratic potential of the new venues becomes magnified, and draws attention to the importance of examining the dynamics underlying the transition of discussion venues.     

Bayesian network analysis for the dynamic prediction of early stage entrepreneurial activity index

Entrepreneurship plays a critical role for the development and well-being of society. Illustration of its dynamic relationship with entrepreneurial attitudes and aspirations can provide a guideline for the cause of such activities. However, a time-lagged causal relationship among these concepts has not yet been established. In this study, we examine a dynamic relationship among early stage entrepreneurial attitudes, activities, and aspirations using Bayesian network (BN) analysis. In addition, we propose an early stage entrepreneurial activity index that can predict the percentage of both nascent entrepreneur and new business owner using the variables related to entrepreneurial attitudes of the previous year. This index, in turn, can be used to predict various aspects of entrepreneurial aspiration of the following year. The proposed index turns out to have very high prediction accuracy and is expected to provide effective policies to boost future entrepreneurial activity and aspiration.     

Extended Process to Product Modeling (xPPM) for integrated and seamless IDM and MVD development

This paper proposes a new extended Process to Product Modeling (xPPM) method for integrated and seamless information delivery manual (IDM) and model view definition (MVD) development. Current IDM development typically uses Business Process Modeling Notation (BPMN) to represent a process map (PM). Exchange requirements (ERs) and functional parts (FPs) specify the information required when information is exchanged between different activities. A set of information requirements, specifically defined as a subset of Industry Foundation Classes (IFC), is called an MVD. Currently however, PMs, ERs, FPs, and MVDs are developed as separate documents through independent development steps. Moreover, even though ERs and FPs are designed to be reused, tracking and reusing the ERs and FPs developed by others is practically impossible. The xPPM method is proposed to provide a tight connection between PMs, ERs, FPs, and MVDs and to improve the reusability of predefined ERs and FPs. The theoretical framework is based on the approach of the Georgia Tech Process to Product Modeling (GTPPM) to suit the IDM development process. An xPPM tool is developed, and the validity of xPPM is analyzed through the reproduction of existing IDMs and MVDs. The benefits and limitations of xPPM and lessons from the applicability tests are discussed.     

Synthesis and characterization of La2Ti2O7 employed for photocatalytic degradation of reactive red 22 dyestuff in aqueous solution

Perovskite structured La₂Ti₂O₇ catalyst prepared by polymerized complex method was characterized and examined the photocatalytic activity by decomposing an azo dyestuff, Reactive Red 22, in aqueous solutions under UV irradiation. La₂Ti₂O₇ powders prepared by polymerized complex method exhibit higher surface areas, better homogeneity and are more sensitive to solution than those prepared by solid-state method. The first derivatives of UV–vis DRS patterns confirmed the complete crystallization of La₂Ti₂O₇ sintered at temperatures higher than 900 °C. The effects of sintering temperature of catalyst and solution pH of photocatalytic reaction were studied. The photocatalytic decomposition of Reactive Red 22 per unit surface area was found to be higher for experiments using La₂Ti₂O₇ than using TiO₂. However, the electron–hole recombination was found to be more obvious for La₂Ti₂O₇ than for TiO₂ because the network of metal cations constructed within La₂Ti₂O₇ enhances the mobility of photogenerated electrons and holes.     

Multifinality in implicit choice.

This research examines the possibility that people's choices in the service of an explicit focal goal may also reflect their tendency to fulfill implicit background goals and in that sense are multifinal. We carried out 5 experimental studies to investigate this notion. In Experiment 1, a primed implicit goal affected individuals' choices even when those avowedly served an explicit “focal” goal. Experiment 2 replicated this finding with a different type of implicit goals. Experiment 3 found that primed implicit goals had no effect on choices where the options that served them undermined the explicit goal. Experiment 4 found that a primed implicit goal served by a multifinal option does not privilege it over a unifinal option if that goal had been already attained by a different means. Finally, Experiment 5, via 3 types of control groups, showed that choices were affected by both the explicit and implicit goals in isolation, and they shifted toward multifinality when these goals were conjointly present. The discussion considers the integrative potential of the multifinality framework and its implications for a variety of phenomena in the domain of motivated cognition. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Canadian counselling psychology: From defining moments to ways forward.

Counselling psychology in Canada is a distinct and vibrant professional area representing the contributions of many people and events within a unique context. This article elaborates a number of defining moments or actions that reveal the distinct nature of this professional area through a recursive and interactive process with the social context. A number of ways forward are proposed as specific professional developments, as well as the resolution of a number of substantive issues identified within the recently adopted definition of counselling psychology. Moving forward as a discipline and a practice will actualize the potential of counselling psychology as both world and life enhancing. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

A Composite Formation Route to Well‐Crystalline Manganese Oxide Nanocrystals: High Catalytic Activity of Manganate–Alumina Nanocomposites

Manganese oxide nanocrystals are combined with aluminum oxide nanocrystals to improve their crystallinity via calcination without a significant increase of crystal size. A nanocomposite, consisting of two metal oxides, can be synthesized by the reaction between permanganate anions and aluminum oxyhydroxide keggin cations. The as‐prepared manganese oxide–aluminum oxide nanocomposite is X‐ray amorphous whereas heat‐treatment gives rise to the crystallization of an α‐MnO₂ phase at 600 °C and Mn₃O₄/Mn₂O₃ and γ‐Al₂O₃ phases at 800 °C. Electron microscopy and N₂ adsorption‐desorption‐isotherm analysis clearly demonstrate that the as‐prepared nanocomposite is composed of a porous assembly of monodisperse primary particles with a size of ～20 nm and a surface area of >410 m² g^?1. Of particular interest is that the small particle size of the as‐prepared nanocomposite is well‐maintained up to 600 °C, a result of the prevention of the growth of manganate grains through nanoscale mixing with alumina grains. The calcined nanocomposite shows very‐high catalytic activity for the oxidation of cyclohexene with an extremely high conversion efficiency of >95% within 15 min. The present results show that the improvement of the crystallinity without significant crystal growth is very crucial for optimizing the catalytic activity of manganese oxide nanocrystals.