Network analysis of human vitiligo scRNA-seq data reveals complex mechanisms of immune activation

The advent of scRNA-seq has rapidly advanced our understanding of complex systems by enabling the researcher to look at the full transcriptional profile within each cell, with the potential to reveal intercellular communications within a tissue. To map these communications, I created SignallingSingleCell, an R package that provides an end-to-end approach for the analysis of scRNA-seq data, with a particular focus on building ligand and receptor signaling networks. Using these powerful techniques, we sought to dissect the heterogenous population of cells recently reported within the BMDC culture system. From this data we were able to determine the cell type composition, identify the different myeloid responses to similar stimuli, and unify recent conflicting studies about the populations within this system. We then applied these tools to study vitiligo, an autoimmune disease of the skin, to answer fundamental questions about the initiation and progression of disease. We found signatures of increased antigen presentation through MHC-I, loss of immunotolerance cytokines such as TGFB1 and IL-10, and changes in the complex chemokine circuits that influence T cell localization, including an essential role for CCR5 in Treg function. In order to identify and characterize the autoreactive T cells that are responsible for the targeted destruction of melanocytes, we then paired scRNA-seq with TCR-seq and MHC-II complexes loaded with melanocyte antigen. From this data we contrast the transcriptional state of melanocyte specific T cells to bystanders found within the skin and circulation

A post trek exploratory study on the physical and psychological ill health effects of trekking to Everest base camp following observations by the author

The purpose of this retrospective study was to understand and test the theory that multiple physical and psychological ill health effects occur when trekking at high altitude to Everest Base Camp (EBC), Nepal. The tour operator, The Adventure Company, agreed to send out 100 questionnaires to clients who had undertaken either the 11 day trek via Tengboche or the 16 day via Goyko Lakes, to EBC. The questionnaires also considered: age, gender, general levels of fitness and previous experience of trekking at altitude. The respondents (n=49) were 53% male (n = 26) and 45% female (n=22) and one unknown. Of the 49 participants, 36 lost weight (p < 0.001) sd ± 2.95 of which 17 were males (p < 0.001) sd ± 2.6 and 19 were females (p <0.001) sd ± 3.3. Altitude sickness was experienced by 38 trekkers or 78% (p < 0.001) using the Lake Louise Score for Acute Mountain Sickness (AMS); 35% (n=17) had mild AMS, 43% (n=21) had severe AMS. The incidence of other conditions was: bacterial infections = (n= 31) or 57% (p < 0.001); general heart rate (n=26) or 55% (p<0.0001); and 71% (n=35) heart rate at night (p <0.0001); low mood = (n=16) or 33% (p< 0.001). The incidence of AMS was higher on reaching 4000m and was consistent with the literature. Other factors identified and consistent with the literature included: significant weight loss; bacterial infections; increase in heart rate in general and at night. Low mood was present during the trek and for some people continued on returning home and has not been well documented in other studies reviewed. Further research on the multiple ill health effects of trekking and how they may be prevented or better managed is needed to reduce risk and aid overall enjoyment

RNAi Validation of Resistance Genes and Their Interactions in the Highly DDT-Resistant 91-R Strain of Drosophila Melanogaster

4,4’-dichlorodiphenyltrichloroethane (DDT) has been re-recommended by the World Health Organization for malaria mosquito control. Previous DDT use has resulted in resistance, and with continued use resistance will increase in terms of level and extent. Drosophila melanogaster is a model dipteran that has many available genetic tools, numerous studies done on insecticide resistance mechanisms, and is related to malaria mosquitoes allowing for extrapolation. The 91-R strain of D. melanogaster is highly resistant to DDT (\u3e1500-fold), however, there is no mechanistic scheme that accounts for this level of resistance. Recently, reduced penetration, increased detoxification, and direct excretion have been identified as resistance mechanisms in the 91-R strain. Their interactions, however, remain unclear. Use of UAS-RNAi transgenic lines of D. melanogaster allowed for the targeted knockdown of genes putatively involved in DDT resistance and has validated the role of several cuticular proteins (Cyp4g1 and Lcp1), cytochrome P450 monooxygenases (Cyp6g1 and Cyp12d1), and ATP binding cassette transporters (Mdr50, Mdr65, and Mrp1) involved in DDT resistance

The Evaluation of the Clinical and Electrocardiographic Findings in Coronary Insufficiency

Abstract Not Provided

Physiological, Cognitive, And Behavioural Effects Of Assigned Performance Goals

The general purpose of this research was to determine whether changes in physiological arousal could be induced in a goal-setting paradigm, and if so, were these changes associated with the cognitive and behavioural effects of assigned performance goals. Two laboratory experiments were conducted to examine the effect of different goal conditions on physiological (skin resistance level and heart rate) and self-report arousal, cognition (performance expectancy/self-efficacy, performance valence, perceived norm, and personal goal), and task performance. In the first experiment subjects performed a simple perceptual-speed task under one of three goal conditions and one of two feedback conditions. In accordance with previous research, the results showed that subjects assigned more difficult goals reported higher performance expectancy (self-efficacy), anticipated satisfaction with higher performance levels, perceived higher norms, set higher personal goals, and outperformed subjects assigned easier goals. Of particular note was the finding that changes in sympathetically-mediated heart rate reflected the level of assigned goal difficulty, and heart rate was positively related to performance expectancy (self-efficacy), perceived norm, and personal goal. This research also showed that providing subjects with quality feedback during task performance increased performance expectancy, the level of personal (self-set) goals, and error-free performance. These findings concur with studies revealing the effects of feedback on goal choice and task performance, and highlight the importance of providing subjects with feedback appropriate for the task and the performance criteria. A second experiment was conducted to clarify the psychological significance of the change in heart rate, and to examine whether changes in heart rate, cognition, and behaviour were associated with need achievement. Results revealed that need achievement was positively related to performance expectancy, perceived norm, and the level of goal choice. The findings of this research have implications for the integration of Goal-Setting Theory with physiologically-based theories of motivation, attention, and effort expenditure, and for job or task design

Structural and dynamic analysis of the Apollo AFT heat shield Final report, Sep. 12, 1964 - Mar. 1, 1966

Structural and dynamic analysis of Apollo aft heat shiel

What's in a Name? Name Choice, Agency, and Identity

This qualitative study addresses name choice among Chinese/Chinese-heritage students at two Ontario universities by asking if identity perception impacts the decision to maintain/change a name and who has agency in these naming choices. Ten out of the 11 participants opted for name change. Six participants attributed English name change to their teachers/education system in China; four asserted full agency in name choice; five were told to choose an English name, but selected their own; and two participants claimed no agency in either change or choice. Based on a grounded theory analysis, social and cultural capital (Bourdieu, 1992), Chinese naming habitus within a Canadian field (Bourdieu, 1984), and agency emerged as strong themes. Through these themes, participants’ negotiation of the third space (Bhabha, 1994) became apparent. This study suggests a need for teachers to gain cultural onomastic awareness so as to respect naming choices and agency of students in Canadian classrooms

Looming motion primes the visuomotor system.

A wealth of evidence now shows that human and animal observers display greater sensitivity to objects that move toward them than to objects that remain static or move away. Increased sensitivity in humans is often evidenced by reaction times that increase in rank order from looming, to receding, to static targets. However, it is not clear whether the processing advantage enjoyed by looming motion is mediated by the attention system or the motor system. The present study investigated this by first examining whether sensitivity is to looming motion per se or to certain monocular or binocular cues that constitute stereoscopic motion in depth. None of the cues accounted for the looming advantage. A perceptual measure was then used to examine performance with minimal involvement of the motor system. Results showed that looming and receding motion were equivalent in attracting attention, suggesting that the looming advantage is indeed mediated by the motor system. These findings suggest that although motion itself is sufficient for attentional capture, motion direction can prime motor responses. © 2013 American Psychological Association

The effect of spatial competition between object-level representations of target and mask on object substitution masking

One of the processes determining object substitution masking (OSM) is thought to be the spatial competition between independent object file representations of the target and mask (e.g., Kahan & Lichtman, 2006). In a series of experiments, we further examined how OSM is influenced by this spatial competition by manipulating the overlap between the surfaces created by the modal completion of the target (an outline square with a gap in one of its sides) and the mask (a four-dot mask). The results of these experiments demonstrate that increasing the spatial overlap between the surfaces of the target and mask increases OSM. Importantly, this effect is not caused by the mask interfering with the processing of the target features it overlaps. Overall, the data indicate, consistent with Kahan and Lichtman, that OSM can arise through competition between independent target and mask representation