Quantitative Proteomics of Polarised Macrophages Derived from Induced Pluripotent Stem Cells

Macrophages (M(Φ)) are highly heterogenous and versatile innate immune cells involved in homeostatic and immune responses. Activated M(Φ) can exist in two extreme phenotypes: pro-inflammatory (M1) M(Φ) and anti-inflammatory (M2) M(Φ). These phenotypes can be recapitulated in vitro by using ligands of toll-like receptors (TLRs) and cytokines such as IFNγ and IL-4. In recent years, human induced pluripotent stem cells (iPSC)-derived M(Φ) have gained major attention, as they are functionally similar to human monocyte-derived M(Φ) and are receptive to genome editing. In this study, we polarised iPSC-derived M(Φ) to M1 or M2 and analysed their proteome and secretome profiles using quantitative proteomics. These comprehensive proteomic data sets provide new insights into functions of polarised M(Φ)

Breast cancer care in Alberta: a Patients perspective

Introduction Each year in Alberta, over 2,300 women are affected by breast cancer. In Alberta, a multi-year Breast Health Initiative is underway to improve breast cancer care; reduce wait times, coordinate care, and enhance patient experience. Patient reported experience measurements are important to inform and advance patient and family-centred care. Objectives and Approach The aim is to assess breast cancer patients’ experiences at two survey points; after surgeon consult and after breast surgery. Patients meeting inclusion criteria; highly suspicious of cancer on imaging result (i.e. BI-RADS 5), referral to Calgary or Edmonton breast program, English speaking, and having an email address are recruited by RN coordinators or nurse navigators. Automated survey invitations from REDCap are used. Seven days after the surgeon consult the first survey is sent and seven days after breast surgery the second survey is sent. Results Patient recruitment began November 27, 2017 and January 2, 2018 for Edmonton and Calgary, respectively. As of February, 2018, 45 patients had been recruited. Of these, the first survey was sent to 34 (i.e. seven days post surgeon consult) and 19 (56%) had completed the survey. All those eligible (18) agreed to participate in the upcoming second survey. Of those, six had provided their surgery date and the second survey which both were completed. Recruitment is ongoing until the conference, at that time there will be sufficient numbers to report findings. Conclusion/Implications Patient and family-centred care is an element of high-quality healthcare which AHS has identified as a priority. These results will report on the breast cancer patients’ perspectives and generate important information for clinicians and administrators to use for decision making and quality improvement of health services

Documentation of breakthrough pain in narrative clinical records of children with life-limiting conditions : feasibility of a retrospective review

This study explored the feasibility of generating reliable information on the frequency, nature and management of breakthrough pain (BTP) in children with life-limiting conditions (LLCs) and life threatening illnesses (LTIs) from narrative clinical records. In the absence of standardised ways for documenting BTP, we conducted a consensus exercise, to develop a glossary of terms that could denote BTP in the records. Thirteen clinicians who contributed to the records reached consensus on 45 terms which could denote BTP, whilst emphasising the importance of contextual information. The results of this approach together with guidance for improving the reliability of retrospective reviews informed a data extraction instrument. A pilot test of this instrument showed poor agreement between raters. Given the challenges encountered, we do not recommend a retrospective review of BTP using narrative records. This study highlighted challenges of data extraction for complex symptoms such as BTP from narrative clinical records. For both clinical and research purposes, the recording of complex symptoms such as BTP would benefit from clear criteria for applying definitions, a more structured format and the inclusion of validated assessment tools. This study also showed the value of consensus exercises in improving understanding and interpretation of clinical notes within a service

Neuronal pentraxin II is highly upregulated in Parkinson’s disease and a novel component of Lewy bodies

Neuronal pentraxin II (NPTX2) is the most highly upregulated gene in the Parkinsonian substantia nigra based on our whole genome expression profiling results. We show here that it is a novel component of Lewy bodies and Lewy neurites in sporadic Parkinson’s disease (PD). NPTX2 is also known as the neuronal activity-regulated protein (Narp), which is secreted and involved in long-term neuronal plasticity. Narp further regulates AMPA receptors which have been found to mediate highly selective non-apoptotic cell death of dopaminergic neurons. NPTX2/Narp is found in close association with alpha-synuclein aggregates in both substantia nigra and cerebral cortex in PD but unlike alpha-synuclein gene expression, which is down-regulated in the Parkinsonian nigra, NPTX2 could represent a driver of the disease process. In view of its profound (>800%) upregulation and its established role in synaptic plasticity as well as dopaminergic nerve cell death, NPTX2 is a very interesting novel player which is likely to be involved in the pathway dysregulation which underlies PD

"Girls can't play": The effects of stereotype threat on females' gaming performance

The current study examined the impact of stereotype threat on female online gamers' performance and further examined whether manipulating the availability of multiple social identities effectively eliminated these performance decrements. Further, participants' implicit attitudes towards female online gamers were assessed. Eighty-one participants (60 female) were assigned to one of four experimental conditions: 1), stereotype threat, 2), multiple social identities, 3), female control, and 4), male control. They completed an Implicit Association Test and a gaming task. The number of coins collected in a 5-min time period provided a measure of gameplay performance. Results indicated that stereotype threatened females underperformed on the gaming task relative to males in the control condition. The intervention of multiple social identities successfully protected females' gameplay performance from stereotype threat. Additionally, differences were found between conditions in implicit attitudes pertaining to gender-gaming competence. This research highlights the harmful effects of negative stereotypes on females' gaming performance, and suggests that these decrements may be eliminated when females identify with an alternative positive social identity

Applying the multi-threat framework of stereotype threat in the context of digital gaming.

Females often report experiencing stigmatisation pertaining to their competency in digital gaming communities. Employing the principles of the multi-Threat framework of stereotype threat, the current research examined the impact of gender-related stereotypes on females' gaming performance and related self-perceptions. In Experiment 1, 90 females were assigned to one of three conditions in which they were primed that their performance would be either diagnostic of their personal (self-As-Target) or gender group's ability (group-As-Target) or would be non-diagnostic of gaming ability (control). In Experiment 2, 90 females were primed that their performance would be judged by a group of other females (in-group source) or males (out-group source), or would be non-diagnostic of ability (control). Participants then completed a casual gaming task, as well as measures of competence beliefs, self-efficacy and self-esteem. Findings from Experiment 1 indicate that neither a self-As-Target nor a group-As-Target stereotype affected significantly gaming performance, or gamerelated self-efficacy, self-esteem and competency beliefs. Findings from Experiment 2 reveal further that females' gaming performance and associated self-perceptions were not impacted significantly by an in-group or out-group source of stereotype threat. The discussion turns to potential explanations for these findings, proposing that females may not perceive negative gender-gaming stereotypes to be an accurate representation of their personal or social group's gaming ability. We also discuss the implications of the experimental design and difficulty, as well as the potential for domain identification to moderate performance outcomes under stereotype threat

Role of Matrix Metalloproteinases and Therapeutic Benefits of Their Inhibition in Spinal Cord Injury

This review will focus on matrix metalloproteinases (MMPs) and their inhibitors in the context of spinal cord injury (SCI). MMPs have a specific cellular and temporal pattern of expression in the injured spinal cord. Here we consider their diverse functions in the acutely injured cord and during wound healing. Excessive activity of MMPs, and in particular gelatinase B (MMP-9), in the acutely injured cord contributes to disruption of the blood-spinal cord barrier, and the influx of leukocytes into the injured cord, as well as apoptosis. MMP-9 and MMP-2 regulate inflammation and neuropathic pain after peripheral nerve injury and may contribute to SCI-induced pain. Early pharmacologic inhibition of MMPs or the gelatinases (MMP-2 and MMP-9) results in an improvement in long-term neurological recovery and is associated with reduced glial scarring and neuropathic pain. During wound healing, gelatinase A (MMP-2) plays a critical role in limiting the formation of an inhibitory glial scar, and mice that are genetically deficient in this protease showed impaired recovery. Together, these findings illustrate complex, temporally distinct roles of MMPs in SCIs. As early gelatinase activity is detrimental, there is an emerging interest in developing gelatinase-targeted therapeutics that would be specifically tailored to the acute injured spinal cord. Thus, we focus this review on the development of selective gelatinase inhibitors

Application of Ligninolytic Enzymes in the Production of Biofuels from Cotton Wastes

The application of ligninolytic fungi and enzymes is an option to overcome the issues related with the production of biofuels using cotton wastes. In this dissertation, the ligninolytic fungus and enzymes were evaluated as pretreatment for the biochemical conversion of Cotton Gin Trash (CGT) in ethanol and as a treatment for the transformation of cotton wastes biochar in other substances. In biochemical conversion, seven combinations of three pretreatments (ultrasonication, liquid hot water and ligninolytic enzymes) were evaluated on CGT. The best results were achieved by the sequential combination of ultrasonication, hot water, and ligninolytic enzymes with an improvement of 10% in ethanol yield. To improve these results, alkaline-ultrasonication was evaluated. Additionally, Fourier Transform Infrared (FT-IR) and principal component analysis (PCA) were employed as fast methodology to identify structural differences in the biomass. The combination of ultrasonication-alkali hydrolysis, hot liquid water, and ligninolytic enzymes using 15% of NaOH improved 35% ethanol yield compared with the original treatment. Additionally, FT-IR and PCA identified modifications in the biomass structure after different types of pretreatments and conditions. In thermal conversion, this study evaluated the biodepolymerization of cotton wastes biochar using chemical and biological treatments. The chemical depolymerization evaluated three chemical agents (KMnO4, H2SO4, and NaOH), with three concentrations and two environmental conditions. The sulfuric acid treatments performed the largest transformations of the biochar solid phase; whereas, the KMnO4 treatments achieved the largest depolymerizations. The compounds released into the liquid phase were correlated with fulvic and humic acids and silicon compounds. The biological depolymerization utilized four ligninolytic fungi Phanerochaete chrysosporium, Ceriporiopsis subvermispora, Postia placenta, and Bjerkandera adusta. The greatest depolymerization was obtained by C. subvermispora. The depolymerization kinetics of C. subvermispora evidenced the production of laccase and manganese peroxidase and a correlation between depolymerization and production of ligninolytic enzymes. The modifications obtained in the liquid and solid phases showed the production of humic and fulvic acids from the cultures with C. subvermispora. The results of this research are the initial steps for the development of new processes using the ligninolytic fungus and their enzymes for the production of biofuels from cotton wastes

Introduction to classical and modern test theory/ Crocker

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