The Many Faces of Matrix Metalloproteinase-7 in Kidney Diseases

Matrix metalloproteinase-7 (MMP-7) is a secreted zinc-dependent endopeptidase that is implicated in regulating kidney homeostasis and diseases. MMP-7 is produced as an inactive zymogen, and proteolytic cleavage is required for its activation. MMP-7 is barely expressed in normal adult kidney but upregulated in acute kidney injury (AKI) and chronic kidney disease (CKD). The expression of MMP-7 is transcriptionally regulated by Wnt/β-catenin and other cues. As a secreted protein, MMP-7 is present and increased in the urine of patients, and its levels serve as a noninvasive biomarker for predicting AKI prognosis and monitoring CKD progression. Apart from degrading components of the extracellular matrix, MMP-7 also cleaves a wide range of substrates, such as E-cadherin, Fas ligand, and nephrin. As such, it plays an essential role in regulating many cellular processes, such as cell proliferation, apoptosis, epithelial-mesenchymal transition, and podocyte injury. The function of MMP-7 in kidney diseases is complex and context-dependent. It protects against AKI by priming tubular cells for survival and regeneration but promotes kidney fibrosis and CKD progression. MMP-7 also impairs podocyte integrity and induces proteinuria. In this review, we summarized recent advances in our understanding of the regulation, role, and mechanisms of MMP-7 in the pathogenesis of kidney diseases. We also discussed the potential of MMP-7 as a biomarker and therapeutic target in a clinical setting

High speed synchrotron X-ray imaging studies of the ultrasound shockwave and enhanced flow during metal solidification processes

The highly dynamic behaviour of ultrasonic bubble implosion in liquid metal, the multiphase liquid metal flow containing bubbles and particles, and the interaction between ultrasonic waves and semisolid phases during solidification of metal were studied in situ using the complementary ultrafast and high speed synchrotron X-ray imaging facilities housed respectively at the Advanced Photon Source, Argonne National Laboratory, US, and Diamond Light Source, UK. Real-time ultrafast X-ray imaging of 135,780 frames per second (fps) revealed that ultrasonic bubble implosion in a liquid Bi-8 wt. %Zn alloy can occur in a single wave period (30 kHz), and the effective region affected by the shockwave at implosion was 3.5 times the original bubble diameter. Furthermore, ultrasound bubbles in liquid metal move faster than the primary particles, and the velocity of bubbles is 70 ~ 100% higher than that of the primary particles present in the same locations close to the sonotrode. Ultrasound waves can very effectively create a strong swirling flow in a semisolid melt in less than one second. The energetic flow can detach solid particles from the liquid-solid interface and redistribute them back into the bulk liquid very effectively

Exploring the impact of group identity at university on psychological and behavioural outcomes

With respect to supporting student well-being and success, the current research developed a peer support scheme, built on the principles of Social Identity Theory (SIT). This was targeted towards first year undergraduate psychology students, in which measures of collective identity, sense of belonging, group efficacy, happiness and resilience were obtained, along with attendance and academic attainment. Following one academic year of being part of our peer support scheme, participants (N= 90) completed a questionnaire and consented to their attendance and attainment data to be used. It was found that students’ collective identity was positively related to their sense of belonging, group efficacy beliefs and happiness. Further, the sense of belonging was a reliable predictor of happiness, but not attendance or academic attainment. Therefore, there is some evidence to suggest that a SIT-driven peer support scheme can support students’ psychosocial well-being, although more is needed to ascertain whether this could be developed further to observe any course-related outcomes. Theoretical contributions to SIT are therefore presented, in which the insights can be applied to Higher Education beyond the UK

Comparison of Pharmacy Students' Perception of Learning Experiences in Inter-professional Education in the Philippines and Indonesia

Background : The inclusion of Interprofessional Education (IPE) in pharmacy schools has long been recommended by American Association of Colleges of Pharmacy and its constituents to provide faculty and students the opportunity for collaborative practice. However, IPE has not been fully embraced in all pharmacy schools. The University of the Philippines Manila (UPM) College of Pharmacy and Universitas Ahmad Dahlan (UAD) Faculty of Pharmacy in Yogyakarta, Indonesia were among the first in Asia to incorporate IPE in their respective countries. Objective : The objective of the study is to compare the perception of the learning experiences of pharmacy students of UPM and UAD. Findings from this study may provide an indication whether IPE is an effective teaching strategy to make pharmacy students “collaborative practice-ready” graduates regardless of the healt professions they worked with, scope of IPE experience, and the location of IPE. Methodology : The study is a quantitative, comparative pre- and post-intervention which utilized the validated questionnaire by Luecht (1990). This was administered to fifteen (15) UPM and eighteen (18) UAD first batch of pharmacy students who participated in IPE in 2014 and 2015, respectively. Result and Conclusion : The results showed high scores for both universities but UPM students have consistently improved scores in terms of autonomy, competency, perceived need for cooperation, and understanding the roles of others. The differences in the results may have been contributed by the small sample size, results being self-reports, established IPE program in UPM, diversity of the team, and previous experience of faculty preceptors handling multidisciplinary teams. Despite the differences, the study still showed that IPE can be a valuable tool in producing “collaborative practice-ready” pharmacy graduates who can promote better patient and community outcomes. Keyword : inteprofessional education, pharmacy IPE, collaborative practic

Pneumococcal conjugate vaccine implementation in middle-income countries

Since 2000, the widespread adoption of pneumococcal conjugate vaccines (PCVs) has had a major impact in the prevention of pneumonia. Limited access to international financial support means some middle-income countries (MICs) are trailing in the widespread use of PCVs. We review the status of PCV implementation, and discuss any needs and gaps related to low levels of PCV implementation in MICs, with analysis of possible solutions to strengthen the PCV implementation process in MICs

Distinct Genetic Lineages of Bactrocera caudata (Insecta: Tephritidae) Revealed by COI and 16S DNA Sequences

The fruit fly Bactrocera caudata is a pest species of economic importance in Asia. Its larvae feed on the flowers of Cucurbitaceae such as Cucurbita moschata. To-date it is distinguished from related species based on morphological characters. Specimens of B. caudata from Peninsular Malaysia and Indonesia (Bali and Lombok) were analysed using the partial DNA sequences of cytochrome c oxidase subunit I (COI) and 16S rRNA genes. Both gene sequences revealed that B. caudata from Peninsular Malaysia was distinctly different from B. caudata of Bali and Lombok, without common haplotype between them. Phylogenetic analysis revealed two distinct clades, indicating distinct genetic lineage. The uncorrected ‘p’ distance for COI sequences between B. caudata of Malaysia-Thailand-China and B. caudata of Bali-Lombok was 5.65%, for 16S sequences from 2.76 to 2.99%, and for combined COI and 16S sequences 4.45 to 4.46%. The ‘p’ values are distinctly different from intraspecific ‘p’ distance (0–0.23%). Both the B. caudata lineages are distinctly separated from related species in the subgenus Zeugodacus – B. ascita, B. scutellata, B. ishigakiensis, B. diaphora, B. tau, B. cucurbitae, and B. depressa. Molecular phylogenetic analysis indicates that the B. caudata lineages are closely related to B. ascita sp. B, and form a clade with B. scutellata, B. ishigakiensis, B. diaphora and B. ascita sp. A. This study provides additional baseline for the phylogenetic relationships of Bactrocera fruit flies of the subgenus Zeugodacus. Both the COI and 16S genes could be useful markers for the molecular differentiation and phylogenetic analysis of tephritid fruit flies

The Histone Demethylase Jarid1b (Kdm5b) Is a Novel Component of the Rb Pathway and Associates with E2f-Target Genes in MEFs during Senescence

Senescence is a robust cell cycle arrest controlled by the p53 and Rb pathways that acts as an important barrier to tumorigenesis. Senescence is associated with profound alterations in gene expression, including stable suppression of E2f-target genes by heterochromatin formation. Some of these changes in chromatin composition are orchestrated by Rb. In complex with E2f, Rb recruits chromatin modifying enzymes to E2f target genes, leading to their transcriptional repression. To identify novel chromatin remodeling enzymes that specifically function in the Rb pathway, we used a functional genetic screening model for bypass of senescence in murine cells. We identified the H3K4-demethylase Jarid1b as novel component of the Rb pathway in this screening model. We find that depletion of Jarid1b phenocopies knockdown of Rb1 and that Jarid1b associates with E2f-target genes during cellular senescence. These results suggest a role for Jarid1b in Rb-mediated repression of cell cycle genes during senescence

Matrix Metalloproteinase-10 Is Required for Lung Cancer Stem Cell Maintenance, Tumor Initiation and Metastatic Potential

Matrix metalloproteinases (Mmps) stimulate tumor invasion and metastasis by degrading the extracellular matrix. Here we reveal an unexpected role for Mmp10 (stromelysin 2) in the maintenance and tumorigenicity of mouse lung cancer stem-like cells (CSC). Mmp10 is highly expressed in oncosphere cultures enriched in CSCs and RNAi-mediated knockdown of Mmp10 leads to a loss of stem cell marker gene expression and inhibition of oncosphere growth, clonal expansion, and transformed growth in vitro. Interestingly, clonal expansion of Mmp10 deficient oncospheres can be restored by addition of exogenous Mmp10 protein to the culture medium, demonstrating a direct role for Mmp10 in the proliferation of these cells. Oncospheres exhibit enhanced tumor-initiating and metastatic activity when injected orthotopically into syngeneic mice, whereas Mmp10-deficient cultures show a severe defect in tumor initiation. Conversely, oncospheres implanted into syngeneic non-transgenic or Mmp10−/− mice show no significant difference in tumor initiation, growth or metastasis, demonstrating the importance of Mmp10 produced by cancer cells rather than the tumor microenvironment in lung tumor initiation and maintenance. Analysis of gene expression data from human cancers reveals a strong positive correlation between tumor Mmp10 expression and metastatic behavior in many human tumor types. Thus, Mmp10 is required for maintenance of a highly tumorigenic, cancer-initiating, metastatic stem-like cell population in lung cancer. Our data demonstrate for the first time that Mmp10 is a critical lung cancer stem cell gene and novel therapeutic target for lung cancer stem cells

Changes in N-Transforming Archaea and Bacteria in Soil during the Establishment of Bioenergy Crops

Widespread adaptation of biomass production for bioenergy may influence important biogeochemical functions in the landscape, which are mainly carried out by soil microbes. Here we explore the impact of four potential bioenergy feedstock crops (maize, switchgrass, Miscanthus X giganteus, and mixed tallgrass prairie) on nitrogen cycling microorganisms in the soil by monitoring the changes in the quantity (real-time PCR) and diversity (barcoded pyrosequencing) of key functional genes (nifH, bacterial/archaeal amoA and nosZ) and 16S rRNA genes over two years after bioenergy crop establishment. The quantities of these N-cycling genes were relatively stable in all four crops, except maize (the only fertilized crop), in which the population size of AOB doubled in less than 3 months. The nitrification rate was significantly correlated with the quantity of ammonia-oxidizing archaea (AOA) not bacteria (AOB), indicating that archaea were the major ammonia oxidizers. Deep sequencing revealed high diversity of nifH, archaeal amoA, bacterial amoA, nosZ and 16S rRNA genes, with 229, 309, 330, 331 and 8989 OTUs observed, respectively. Rarefaction analysis revealed the diversity of archaeal amoA in maize markedly decreased in the second year. Ordination analysis of T-RFLP and pyrosequencing results showed that the N-transforming microbial community structures in the soil under these crops gradually differentiated. Thus far, our two-year study has shown that specific N-transforming microbial communities develop in the soil in response to planting different bioenergy crops, and each functional group responded in a different way. Our results also suggest that cultivation of maize with N-fertilization increases the abundance of AOB and denitrifiers, reduces the diversity of AOA, and results in significant changes in the structure of denitrification community

Biocontrol Potential of Forest Tree Endophytes

Peer reviewe