Cathepsin K Knockout Mitigates High-Fat Diet–Induced Cardiac Hypertrophy and Contractile Dysfunction

The cysteine protease cathepsin K has been implicated in pathogenesis of cardiovascular disease. We hypothesized that ablation of cathepsin K protects against obesity-associated cardiac dysfunction. Wild-type mice fed a high-fat diet exhibited elevated heart weight, enlarged cardiomyocytes, increased left ventricular wall thickness, and decreased fractional shortening. All these changes were reconciled in cathepsin K knockout mice. Cathepsin K knockout partly reversed the impaired cardiomyocyte contractility and dysregulated calcium handling associated with high-fat diet. Additionally, cathepsin K knockout alleviated whole-body glucose intolerance and improved insulin-stimulated Akt phosphorylation in high-fat diet–fed mice. High-fat feeding increased the expression of cardiac hypertrophic proteins and apoptotic markers, which were inhibited by cathepsin K knockout. Furthermore, high-fat feeding resulted in cathepsin K release from lysosomes into the cytoplasm. In H9c2 myoblasts, silencing of cathepsin K inhibited palmitic acid–induced release of cytochrome c from mitochondria and expression of proapoptotic signaling molecules. Collectively, our data indicate that cathepsin K contributes to the development of obesity-associated cardiac hypertrophy and may represent a potential target for the treatment to obesity-associated cardiac anomalies

Development and verification of time-dependent bounding surface model under metro dynamic loads

To study the dynamic characteristics of soft soil foundation under the long-term metro dynamic loads, modified model based on the bounding surface model was presented. The Mesri creep formula was introduced into the bounding surface model, then it could not only consider the effects of time but also could describe the soil’s arbitrary shear stress levels. The modified bounding surface model was derived using the Newton-Raphson method and the secondary development of the model was conducted. Meanwhile, in order to verify the model, the dynamic triaxial tests of the soft soil were conducted by GDS dynamic triaxial equipment and the metro dynamic loads were simulated during dynamic triaxial tests. Then, the numerical simulation of modified bounding surface model was carried out for soft soil and the numerical results were compared with the test results. The results show that the time-dependent bounding surface model provides a more accurate calculation for the dynamic strain, and establishes a theoretical foundation for predicting the settlement of the soft soil

Experimental investigations of quasi-coherent micro-instabilities in Ohmic plasmas

The ITG and TEM instabilities with quasi-coherent spectra have been identified experimentally, by the newly developed far-forward collective scattering measurements in J-TEXT tokamak Ohmical plasmas. The ITG mode has characteristic frequencies in the range of 30-100kHz and wavenumber of k_\theta\rho_s<0.3. After the plasma density exceeds at critical value, the ITG mode shows a bifurcation behavior, featured by frequency decrease and amplitude enhancement. Meanwhile, the ion energy loss enhancement and confinement degradation are also observed. It gives the direct experimental evidence for ion thermal transport caused by ITG instability

Subtype-Based Analysis of Cell-in-Cell Structures in Esophageal Squamous Cell Carcinoma

Cell-in-cell (CIC) structures are defined as the special structures with one or more cells enclosed inside another one. Increasing data indicated that CIC structures were functional surrogates of complicated cell behaviors and prognosis predictor in heterogeneous cancers. However, the CIC structure profiling and its prognostic value have not been reported in human esophageal squamous cell Carcinoma (ESCC). We conducted the analysis of subtyped CIC-based profiling in ESCC using “epithelium-macrophage-leukocyte” (EML) multiplex staining and examined the prognostic value of CIC structure profiling through Kaplan-Meier plotting and Cox regression model. Totally, five CIC structure subtypes were identified in ESCC tissue and the majority of them was homotypic CIC (hoCIC) with tumor cells inside tumor cells (TiT). By univariate and multivariate analyses, TiT was shown to be an independent prognostic factor for resectable ESCC, and patients with higher density of TiT tended to have longer post-operational survival time. Furthermore, in subpopulation analysis stratified by TNM stage, high TiT density was associated with longer overall survival (OS) in patients of TNM stages III and IV as compared with patients with low TiT density (mean OS: 51 vs 15 months, P = 0.04) and T3 stage (mean OS: 57 vs 17 months, P=0.024). Together, we reported the first CIC structure profiling in ESCC and explored the prognostic value of subtyped CIC structures, which supported the notion that functional pathology with CIC structure profiling is an emerging prognostic factor for human cancers, such as ESCC

Adjuvant-specific regulation of long-term antibody responses by ZBTB20

The duration of antibody production by long-lived plasma cells varies with the type of immunization, but the basis for these differences is unknown. We demonstrate that plasma cells formed in response to the same immunogen engage distinct survival programs depending on the adjuvant. After alum-adjuvanted immunization, antigen-specific bone marrow plasma cells deficient in the transcription factor ZBTB20 failed to accumulate over time, leading to a progressive loss of antibody production relative to wild-type controls. Fetal liver reconstitution experiments demonstrated that the requirement for ZBTB20 was B cell intrinsic. No defects were observed in germinal center numbers, affinity maturation, or plasma cell formation or proliferation in ZBTB20-deficient chimeras. However, ZBTB20-deficient plasma cells expressed reduced levels of MCL1 relative to wild-type controls, and transgenic expression of BCL2 increased serum antibody titers. These data indicate a role for ZBTB20 in promoting survival in plasma cells. Strikingly, adjuvants that activate TLR2 and TLR4 restored long-term antibody production in ZBTB20-deficient chimeras through the induction of compensatory survival programs in plasma cells. Thus, distinct lifespans are imprinted in plasma cells as they are formed, depending on the primary activation conditions. The durability of vaccines may accordingly be improved through the selection of appropriate adjuvants

Effectiveness of Educational Poster to Increase Student Engagement in CAP 2030

Our research aims to explore whether visualization tools such as educational posters increase student engagement in Climate Action Plan 2030 or not. 66 participants were recruited and were randomly assigned into three conditions: poster, text, and control condition. Participants in the poster and text groups were asked to view either posters or texts related to food waste and then surveyed. In contrast, participants in the control condition were only asked to do a survey. Contrary to our hypothesis, we found that the visualization of information did not increase participants' engagement in climate change actions. Disclaimer: “UBC SEEDS provides students with the opportunity to share the findings of their studies, as well as their opinions, conclusions and recommendations with the UBC community. The reader should bear in mind that this is a student project/report and is not an official document of UBC. Furthermore readers should bear in mind that these reports may not reflect the current status of activities at UBC. We urge you to contact the research persons mentioned in a report or the SEEDS Coordinator about the current status of the subject matter of a project/report.”Arts, Faculty ofPsychology, Department ofUnreviewedUndergraduat

Social weather: A review of crowdsourcing‐assisted meteorological knowledge services through social cyberspace

Abstract Crowdsourcing has significantly motivated the development of meteorological services. Starting from the beginning of 2010s and highly motivating after 2014, crowdsourcing‐driven meteorological services have evolved from a single collection and observation of data to the systematic acquisition, analysis and application of these data. In this review, by focusing on papers and databases that have combined crowdsourcing methods to promote or implement meteorological knowledge services, we analysed the relevant literature in three dimensions: data collection, information analysis and meteorological knowledge applications. First, we selected the potential data sources for crowdsourcing and discussed the characteristics of the collected data in four dimensions: consciousness, objectiveness, mobility and multidisciplinary. Second, based on the purpose of these studies and the extent of utilizing data as well as knowledge, we categorize the crowdsourcing‐based meteorological analysis into three levels: relationship discovery, knowledge generalization and systemized service. Third, according to the application scenario, we discussed the applications that have already been put into use, and we suggest current challenges and future research directions. These previous studies show that the use of crowdsourcing in social space can expand the coverage as well as enhance the performance of meteorological service. It was also evident that current researches are contributing towards a systemic and intelligent knowledge service to establish a better bridge among academic, industrial and individual community