Investigating lung function gene GSTCD using gene targeting in human and mouse systems

Respiratory diseases are a significant global health concern and burden, with one of the major respiratory diseases causing a decline in lung function being chronic obstructive pulmonary disease (COPD). Critically, current therapies have limited impact. Recently, single nucleotide polymorphisms at chromosome locus 4q24 have been identified as associated with the lung function measure forced expiratory volume in 1 second and COPD, specifically identifying the gene Glutathione S-transferase C-terminal domain containing (GSTCD) as a viable candidate gene. Data indicate that GSTCD or associated biological pathways may be a potential target for interventions to alleviate COPD. Further analysis into the pathways and phenotypic effects of this gene may aid our understanding of the mechanisms by which GSTCD is associated with and influences lung function and COPD. Importantly, there are currently no reports describing the function of GSTCD, therefore this project aimed to understand the consequences of reduction and loss of GSTCD within the context of lung biology. This was performed by analysis of human cell knock-down and knock-out mouse models respectively, as well as utilising established protein sequence homology analysis to infer potential function. Conclusions drawn from these results suggest a possible role for GSTCD in cell growth in a human in vitro GSTCD knock-down model, but no gross morphological differences were evident in Gstcd knock-out mice. Additionally, GSTCD sequence homology analysis in several protein prediction servers suggests methyltransferase activity as a potential function for GSTCD, differing from the initial prediction of glutathione S-transferase enzyme activity. Overall, this research represents an important and novel development for the lung function and COPD associated gene GSTCD, providing interesting avenues for future exploration

Reshaping graduate outcomes of science students – The contribution of undergraduate research experiences

Today’s science graduates require substantially different skills compared to yesterday’s graduates given the changing nature of modern science. As higher education institutions struggle to reform curricula and pedagogy, undergraduate research experiences (UREs) are increasingly being incorporated to enhance undergraduate science curricula. This study is situated within a traditional Bachelor of Science degree that offers students some voluntary opportunities to participate in UREs. This study explores two graduating science cohorts (n=272), comparing those who did and did not participate in UREs. A survey investigated student perceptions (importance, confidence and improvements) of five graduate outcomes in the context of science: writing skills, communication skills, quantitative skills (QS), teamwork skills and content knowledge. Cross-tabs and a linear discriminant analysis were used to investigate perception change between the two groups. The notable differences in perception scores in this study were consistently higher in QS, perhaps indicative of UREs emphasising the need for such skills in science or from students gaining increased confidence as a result of utilising QS within an authentic context. Our results reveal little difference in other student outcome areas, which raises questions around the role of UREs as a broad strategy for enhancing the achievement of graduate outcomes in science. This study is limited to a single institution and is focused on specific graduate outcomes, so only limited conclusions can be drawn. However, further research to determine the graduate outcomes gained from UREs would benefit the sector, particularly science disciplines, in the changing focus of government policy on student learning outcomes

Defining a role for lung function associated gene GSTCD in cell homeostasis

Genome wide association (GWA) studies have reproducibly identified signals on chromosome 4q24 associated with lung function and COPD. GSTCD (Glutathione S-transferase C-terminal domain containing) represents a candidate causal gene in this locus, however little is currently known about the function of this protein. We set out to further our understanding of the role of GSTCD in cell functions and homeostasis using multiple molecular and cellular approaches in airway relevant cells. Recombinant expression of human GSTCD in conjunction with a GST activity assay did not identify any enzymatic activity for two GSTCD isoforms questioning the assignment of this protein to this family of enzymes. Protein structure analyses identified a potential methyltransferase domain contained within GSTCD, with these enzymes linked to cell viability and apoptosis. Targeted knockdown (siRNA) of GSTCD in bronchial epithelial cells identified a role for GSTCD in cell viability as proliferation rates were not altered. To provide greater insight we completed transcriptomic analyses on cells with GSTCD expression knocked down and identified several differentially expressed genes including those implicated in airway biology; fibrosis e.g. TGFBR1 and inflammation e.g. IL6R. Pathway based transcriptomic analyses identified an over-representation of genes related to adipogenesis which may suggest additional functions for GSTCD. These findings identify potential additional functions for GSTCD in the context of airway biology beyond the hypothesised GST activity and warrant further investigation

A Pilot Study Combining a GC-Sensor Device with a Statistical Model for the Identification of Bladder Cancer from Urine Headspace

There is a need to reduce the number of cystoscopies on patients with haematuria. Presently there are no reliable biomarkers to screen for bladder cancer. In this paper, we evaluate a new simple in-house fabricated, GC-sensor device in the diagnosis of bladder cancer based on volatiles. Sensor outputs from 98 urine samples were used to build and test diagnostic models. Samples were taken from 24 patients with transitional (urothelial) cell carcinoma (age 27-91 years, median 71 years) and 74 controls presenting with urological symptoms, but without a urological malignancy (age 29-86 years, median 64 years); results were analysed using two statistical approaches to assess the robustness of the methodology. A two-group linear discriminant analysis method using a total of 9 time points (which equates to 9 biomarkers) correctly assigned 24/24 (100%) of cancer cases and 70/74 (94.6%) controls. Under leave-one-out cross-validation 23/24 (95.8%) of cancer cases were correctly predicted with 69/74 (93.2%) of controls. For partial least squares discriminant analysis, the correct leave-one-out cross-validation prediction values were 95.8% (cancer cases) and 94.6% (controls). These data are an improvement on those reported by other groups studying headspace gases and also superior to current clinical techniques. This new device shows potential for the diagnosis of bladder cancer, but the data must be reproduced in a larger study. © 2013 Khalid et al

Development of modified apple polysaccharide capped silver nanoparticles loaded with mesalamine for effective treatment of ulcerative colitis

The objective of study was to develop modified apple polysaccharide (MAP) based silver nanoparticles (AgNPs) loaded with mesalamine (MES) for effective treatment of ulcerative colitis in acetic acid induced rat model. AgNPs were prepared by reducing silver nitrate using MAP solution. The size and zeta potential of AgNPs was 89 ± 3 nm and −16.3 ± 1.54 mV and AgNPs loaded with MES (AgNPs-MES) was 101 ± 9 nm and −14.27 ± 2.16 mV. The dissolution study revealed about 54% drug release after 5 h indicating release of drug at the colonic site. The in vivo study was carried out on acetic acid induced ulcerative colitis rats and efficacy of treatment was assessed through evaluation of disease activity index and level of antioxidants as well as tumor necrosis factor-α after 7th and 14th day of induction of colitis. Histopathological evaluation of colonic tissue was also carried out. The results revealed that AgNPs-MES (high dose) provided better therapeutic efficacy for the treatment of UC as compared to its low dose, MES alone, MES-MAP, AgNPs alone and MAP alone. It was concluded that MAP based AgNPs loaded with MES were successfully formulated and found to be effective in treating ulcerative colitis

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid- sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.Integrative Biolog

Gendering the careers of young professionals: some early findings from a longitudinal study. in Organizing/theorizing: developments in organization theory and practice

Wonders whether companies actually have employees best interests at heart across physical, mental and spiritual spheres. Posits that most organizations ignore their workforce – not even, in many cases, describing workers as assets! Describes many studies to back up this claim in theis work based on the 2002 Employment Research Unit Annual Conference, in Cardiff, Wales

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Investigating lung function gene GSTCD using gene targeting in human and mouse systems

Respiratory diseases are a significant global health concern and burden, with one of the major respiratory diseases causing a decline in lung function being chronic obstructive pulmonary disease (COPD). Critically, current therapies have limited impact. Recently, single nucleotide polymorphisms at chromosome locus 4q24 have been identified as associated with the lung function measure forced expiratory volume in 1 second and COPD, specifically identifying the gene Glutathione S-transferase C-terminal domain containing (GSTCD) as a viable candidate gene. Data indicate that GSTCD or associated biological pathways may be a potential target for interventions to alleviate COPD. Further analysis into the pathways and phenotypic effects of this gene may aid our understanding of the mechanisms by which GSTCD is associated with and influences lung function and COPD. Importantly, there are currently no reports describing the function of GSTCD, therefore this project aimed to understand the consequences of reduction and loss of GSTCD within the context of lung biology. This was performed by analysis of human cell knock-down and knock-out mouse models respectively, as well as utilising established protein sequence homology analysis to infer potential function. Conclusions drawn from these results suggest a possible role for GSTCD in cell growth in a human in vitro GSTCD knock-down model, but no gross morphological differences were evident in Gstcd knock-out mice. Additionally, GSTCD sequence homology analysis in several protein prediction servers suggests methyltransferase activity as a potential function for GSTCD, differing from the initial prediction of glutathione S-transferase enzyme activity. Overall, this research represents an important and novel development for the lung function and COPD associated gene GSTCD, providing interesting avenues for future exploration