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Complete Fiction & Life Writing, May 2018
No full textAll prose creative writing from Transnational Literature, May 2018, in one file for ease of printing and downloadin
ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells
Get PDF© The Author(s) 2018 This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Abstract
Objective
Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1 transcript, increasing protein expression. However, studies of ICR involvement in disease have been limited as the promoter is uncharacterized. To address this issue, we undertook a comprehensive in silico analysis of the human ICR gene promoter region.
Results
We used genomic evolutionary rate profiling to identify a 115 base pair (bp) sequence within 500 bp upstream of the transcription start site of the annotated human ICR gene that was conserved across 25 eutherian genomes. A second constrained sequence upstream of the orthologous mouse gene (68 bp; conserved across 27 Eutherian genomes including human) was also discovered. Searching these elements identified 33 matrices predictive of binding sites for transcription factors known to be responsive to a broad range of pathological stimuli, including hypoxia, and metabolic and inflammatory proteins. Five phenotype-associated single nucleotide polymorphisms (SNPs) in the immediate vicinity of these elements included four SNPs (i.e. rs2569693, rs281439, rs281440 and rs11575074) predicted to impact binding motifs of transcription factors, and thus the expression of ICR and ICAM-1 genes, with potential to influence disease susceptibility. We verified that human retinal endothelial cells expressed ICR, and observed induction of expression by tumor necrosis factor-α
Giving institutional voice to work-integrated learning in academic workloads
Get PDFThe International Journal of Work-Integrated Learning is an Open Access journal which means that all content is freely available without charge to the user or his/her institution. Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of Open Access.Little is known about how university institutions are coping with increased placement demands in professional disciplines, and what this means for the quality and integrity of the Work-Integrated Learning (WIL) experiences offered within degree programs for all partners concerned. The first stage of a critical ethnographic study is reported in this paper. It forms part of a larger, ongoing study that seeks to generate critical perspectives on the impact and effects of an inquiry-based WIL philosophy that fosters sustained, meaningful university-community partnerships across a suite of Early Childhood programs. Institutional insights into the workload of university staff responsible for these programs are presented, revealing the complexities and possibilities of what this form of work involves in efforts to sustain meaningful, reciprocal partnerships over time. Findings reveal challenges to the relational foundations of this work and the potential implications for universities to reconsider the nature of their engagement with community in the education of deliberate professionals
Can Exposure to Online Conversations About Death and Dying Influence Death Competence? An Exploratory Study Within an Australian Massive Open Online Course
Get PDFCopyright © 2018 The Authors. Reprinted by permission of SAGE Publications.
This author accepted manuscript is made available following 12 month embargo from date of publication (March 2018) in accordance with the publisher’s archiving policyA Massive Open Online Course, Dying2Learn, was designed to foster community death conversations and strengthen community awareness of palliative care and death as a normal process. This exploratory study used a pre–post prospective design to determine if participation in Dying2Learn and exposure to online conversations about death and dying resulted in any significant influence on death competence in 134 participants who completed the Coping-with-Death-Scale both at the beginning and end of the course in 2016. Death competence refers to a range of attitudes and capabilities people have for dealing with death. Results at the end of the course indicated that engagement in Dying2Learn led to significant improvements in death competence scores over time (medium-to-large effect size). The positive impact was greater for those who completed more of the course, and effectiveness did not depend on sociodemographic characteristics. In conclusion, this study found that an online learning platform in the form of a Massive Open Online Course could engage community members in meaningful social discussion about death and dying, and that exposure to these conversations was beneficial for all participants regardless of previous exposure to death. Further exploration is required to determine whether this change in death competence will have an impact on participant’s behavior in the community regarding death conversations and preparedness
Mainland Chinese students’ mental health: baseline data and cautionary notes when exporting/importing psychological scales
Get PDF“This is an Accepted Manuscript of an article published by Taylor & Francis in Pastoral Care in Education on 29 May 2018, available online: http://www.tandfonline.com/10.1080/02643944.2018.1479569"
© 2018 NAPC.
This author accepted manuscript is made available following 18 month embargo from date of publication (May 2018) in accordance with the publisher’s archiving policyThere is a growing interest in mainland China about schools’ roles in supporting students to develop positive mental health. However, relatively little data have been collected about mainland Chinese students’ mental health. This article reports a collaborative study, by eastern and western researchers, to translate and administer the Strengths and Difficulties Questionnaire (SDQ) and a School Satisfaction Scale (SSS) to students in mainland China. We discuss the possible absence of some western psychological constructs in eastern contexts, and possible cultural differences in the levels of participants’ compliant responses. Descriptive results indicated that the mainland Chinese students’ SDQ responses were similar to students in comparative countries. Factor analyses indicated that the SDQ needed modification when used with our mainland Chinese sample. Structural equation modelling showed relationships between higher school satisfaction and lower mental difficulties. The study provides baseline data to inform school-based mental health promotion initiatives in mainland China. Broader outcomes are to inform researchers and educators about processes and cautions when using previously validated questionnaires in new cultural contexts. We highlight the need for close east–west researcher collaboration when exporting/importing psychological questionnaires
The relationship between anticipated response and subsequent experience of cancer treatment-related side effects: A meta-analysis comparing effects before and after treatment exposure
Get PDF© 2018 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license:
http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (June 2018) in accordance with the publisher’s archiving policyObjective
To review the evidence for a systematic relationship between cancer patients’ pre-treatment expectations (anticipated side effects) and subsequent experience of treatment-related side effects, and to compare this relationship in patients with no prior treatment experience (cognitive expectations) and with some prior treatment experience (conditioned response).
Methods
A total of 12,952 citations were identified through a comprehensive search of the literature published on or before November 2016 and screened against inclusion criteria. Studies were eligible if they included participants undergoing curative treatment for cancer, measured a treatment side effect, examined the relationship between anticipation and experience of side effects, and reported quantitative data.
Results
Thirty-one studies were included in the review and meta-analysis (total N = 5069). The side effects examined were nausea (anticipatory and post-treatment), vomiting, fatigue, pain, problems with concentration, and skin reactions. Meta-analyses indicated positive associations between anticipation and subsequent experience for all included side effects in patients with no prior treatment exposure (r = 0.153–0.431). Stronger associations were found for all included side effects in patients with previous treatment experience (r = 0.211–0.476), except for fatigue (r = 0.266) and pain (r = 0.235). No significant differences were found when overall effect sizes for patients with and without prior treatment exposure were compared for each side effect, except for anticipatory nausea (p = 0.012).
Conclusion
These results may have implications for future interventions that target patients’ expectations of cancer treatment-related side effects. Future research could explore patient reports of messages received about likely treatment effects both before and during treatment
Pulmonary cryptococcal infection presenting with multiple lung nodules
Get PDF© 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).Pulmonary infections from the environmental fungus Cryptococcus gattii (C. gattii) are notable for cryptococcomas,
which are usually solitary and can be very large. As with infections with Cryptococcus neoformans (C.
neoformans) patients can have concomitant cryptococcal meningitis; however, unlike for C. neoformans, infections
with C. gattii often occur in immunocompetent patients. The highest published incidence of C. gattii infection
has been in the Indigenous Australian population of Arnhem Land in the tropical north of the country.
More recently C. gattii has been responsible for outbreaks of cryptococcosis in the Pacific Northwest of Canada
and the United States of America (USA). A previously healthy Indigenous male from Arnhem Land presented
with pulmonary cryptococcosis with chest imaging showing>50 bilateral lung nodules. This unusual occurrence
was attributed to probable inhalation of fungal elements from prior use of a high-pressure leaf blower to
clear eucalyptus and other debris in a remote bush camp
DNA Typing from Skeletal Remains: A Study of Inhibitors using Mass Spectrometry
Get PDF© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license:http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (Sept 2017) in accordance with the publisher’s archiving policyThis project examines the materials co-extracting with DNA from skeletonized remains that have been in the environment for greater than 50 years. A total of 435 samples with known loss locations were collected for this study in the course of ongoing HID processes. During preparation for DNA extraction, a fine powder containing osseous materials and associated environmental detritus was collected from these skeletal elements. Initial results indicate that accelerants and other fuels are not completely removed from DNA extracts using an organic extraction protocol. Portions of this skeletal residue were extracted with multiple solvents and evaporated to concentrate available materials. Samples were rehydrated in methanol and analyzed using a GC/MS. Additionally, the purified DNA from the associated remains was suspended in methanol for comparison. The skeletal materials were a mix of materials present in the environment, by-products of decay (e.g., lipids), and fat-soluble compounds inherent to the remains. Fat-soluble medications (e.g., quinine) were detectable, as were fuels and accelerants. Site-specific biological materials, such as oils from local plants, were also detected. Comparison of skeletal elements from the same site, but not the same individual, showed similar patterns of compounds present with personal variations. Not only is it possible to qualitatively study the presence of DNA inhibitors in real-world situations using GC/MS, but there is the potential to provide an additional metric for individuation or identification of unknown human remains
Identification of novel response and predictive biomarkers to Hsp90 inhibitors through mass spectrometry-based proteomic profiling of patient-derived prostate tumor explants
Get PDFPublished under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.
This research was originally published in Molecular &
Cellular Proteomics.
Nguyen, E. V., Centenera, M. M., Moldovan, M., Das, R.,
Irani, S., Vincent, A. D., … Butler, L. M. Identification of
Novel Response and Predictive Biomarkers to Hsp90
Inhibitors Through Proteomic Profiling of Patient-derived
Prostate Tumor Explants. Mol Cell Proteomics. 2018;
17(8):1470–1486. © the Author(s).Inhibition of the heat shock protein 90 (Hsp90) chaperone is a promising therapeutic
strategy to target expression of the androgen receptor (AR) and other oncogenic
drivers in prostate cancer cells. However, identification of clinically-relevant
responses and predictive biomarkers is essential to maximize efficacy and treatment
personalization. Here, we combined mass spectrometry (MS)-based proteomic
analyses with a unique patient-derived explant (PDE) model that retains the complex
microenvironment of primary prostate tumors. Independent discovery and validation
cohorts of PDEs (n=16 and 30, respectively) were cultured in the absence or
presence of Hsp90 inhibitors AUY922 or 17-AAG. PDEs were analysed by LCMS/
MS with a hyper-reaction monitoring data independent acquisition (HRM-DIA)
workflow, and differentially expressed proteins identified using repeated measure
analysis of variance (ANOVA; raw p-value<0.01). Using gene set enrichment, we
found striking conservation of the most significantly AUY922-altered gene pathways
between the discovery and validation cohorts, indicating that our experimental and
analysis workflows were robust. Eight proteins were selectively altered across both
cohorts by the most potent inhibitor, AUY922, including TIMP1, SERPINA3 and
CYP51A (adjusted p<0.01). The AUY922-mediated decrease in secretory TIMP1
was validated by ELISA of the PDE culture medium. We next exploited the
heterogeneous response of PDEs to 17-AAG in order to detect predictive biomarkers
of response, and identified PCBP3 as a marker with increased expression in PDEs
that had no response or increased in proliferation. Also, 17-AAG treatment led to
increased expression of DNAJA1 in PDEs that exhibited a cytostatic response,
revealing potential drug resistance mechanisms. This selective regulation of
DNAJA1 was validated by western blot analysis. Our study establishes ‘proof-of-principle’ that proteomic profiling of drug-treated PDEs represents an effective and
clinically-relevant strategy for identification of biomarkers that associate with certain
tumor-specific responses.L.M.B., R.J.D., L.G.H. and M.M.C. acknowledge grant support from Cancer
Australia/Prostate Cancer Foundation of Australia (ID 1050880 and 1085471).
M.M.C. was supported by a Young Investigator Award (ID 0412) from the Prostate
Cancer Foundation of Australia; L.M.B. is supported by a Future Fellowship from the
Australian Research Council (FT130101004); and R.J.D. by a National Health and
Medical Research Council Fellowship (1058540). This work was also supported by
an EMBL Australia Group Leader award to D.J.L. The authors thank the Monash
Biomedical Proteomics Facility for technical assistance
Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis
Get PDFThis is an open access
article distributed under the terms of
the Creative Commons Attribution 4.0
International license.Long-term macrolide therapy reduces rates of pulmonary exacerbation in bronchiectasis. However, little is known about the potential for macrolide therapy to alter the composition and function of the oropharyngeal commensal microbiota or to increase the carriage of transmissible antimicrobial resistance. We assessed the effect of long-term erythromycin on oropharyngeal microbiota composition and the carriage of transmissible macrolide resistance genes in 84 adults with bronchiectasis, enrolled in the Bronchiectasis and Low-dose Erythromycin Study (BLESS) 48-week placebo-controlled trial of twice-daily erythromycin ethylsuccinate (400 mg). Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined by 16S rRNA gene amplicon sequencing and quantitative PCR, respectively. Long-term erythromycin treatment was associated with a significant increase in the relative abundance of oropharyngeal Haemophilus parainfluenzae (P = 0.041) and with significant decreases in the relative abundances of Streptococcus pseudopneumoniae (P = 0.024) and Actinomyces odontolyticus (P = 0.027). Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance of Actinomyces spp. (P = 0.046). Erythromycin treatment did not result in a significant increase in the number of subjects who carried erm(A), erm(B), erm(C), erm(F), mef(A/E), and msrA macrolide resistance genes. However, the abundance of erm(B) and mef(A/E) gene copies within carriers who had received erythromycin increased significantly (P < 0.05). Our findings indicate that changes in oropharyngeal microbiota composition resulting from long-term erythromycin treatment are modest and are limited to a discrete group of taxa. Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight the potential for this microbial system to act as a reservoir for resistance.This study was funded by the National Health and Medical Research Council of
Australia (NHMRC project identifier 11044000)