Looking Beyond the Self: Tibetan Buddhist and Navajo Transformation Ceremonies

Sandpaintings are tools used by many cultures to convey a message of religious teaching, universal balance and visual beauty. Through the process of teaching and visualization, the mandala or sandpainting ceremony is of singular importance to the Tibetan Buddhists of Central Asia and to the Navajo people of North America as well. Although sandpaintings provide a visual rendition of a specific teaching or story, and may take many forms, they must be understood as only one component of a much larger ritual event

GROWING TINY PLANTS IN COMMON ENVIRONMENTS: ASSESSING PATTERNS AND MECHANISMS OF DROUGHT RESPONSE WITHIN SPECIES

As climate changes and drought frequency and intensity increases, understanding how plants respond will be critical both for predicting potential for adaptation to future climate and for implementing effective ecosystem conservation and management at a time of rapid change. However, gaps in knowledge about the extent to which species vary in key traits across their ranges and the evolutionary and physiological mechanisms which underlie this variation limits both theoretical understanding and effective management. The broad theme of this dissertation is to address within-species variation both to improve understanding of adaptation to future climate and inform ecosystem conservation and management. The three chapters in this dissertation contribute to a growing body of literature on genetic and plastic variation in key plant traits across environmental gradients, emphasizing the ecological and practical importance of plant trait variation both among and within provenances. Chapter I focused on identifying genetic variation among and within populations of the iconic tree Araucaria araucana (pewen) across its range in Chile to inform conservation and restoration efforts. Chapter II addressed whether within-species genetic and plastic variation in early plant phenotypes impacts drought survival for two Chilean forbs across a significant precipitation gradient. Chapter III synthesized patterns of within-species and across-species variation for a suite of drought response traits. The chapters in this dissertation are particularly timely as research and management efforts increasingly recognize that species are not a monolith and that characterizing the ecologically, genetically, and practically important variation within species is key to understanding adaptation to current and future climate and informing ecosystem management

Sacred and secular leadership discourses : interpreting the leadership of evangelical Christian school leaders

The research enquiry for this thesis, from an insider/outsider position, is a deeply held\ud reflection of personal values, convictions and professional experiences stemming from\ud the researcher's life's work in school leadership both in the United States and abroad.\ud The intent of this study is to engage with the sacred discourse of evangelical Christian\ud school leaders and the discourse of the sacred and secular scholarly literature.\ud This is a qualitative study of a constructivist/interpretivist approach where semistructured\ud interviews, with 12 senior school leaders, four in each of three Anglophone\ud countries, inform the data. A more in-depth case study of one school is utilised as a\ud comprehensive illustration of thematic elements revealed through multiple data sources.\ud The preliminary literature for this research was based on the readings of various\ud contemporary theories of leadership and literature around servant-leadership from which\ud the initial research question was framed. As the data analysis advanced, a new framework\ud emerged around attributes of leadership and community building through leadership,\ud making it imperative to accommodate a new set of transformational/relational/ethical\ud literature, taking the story on a completely different journey with a new research question\ud and sub-questions; therefore, leaving behind the initial research question.\ud Two descriptors of leadership became the primary framework for the thesis: the 'sacred'\ud and the 'secular' discourses relating to school leadership. Standing in the doorway, as it\ud were, the researcher took on a role of interpreting and translating one discourse to the\ud other rather than acting solely as observer and interpreter of the data.\ud The findings, the utilisation of two discourses, and the interpretive stance make a positive\ud and original contribution to knowledge and are significant in two ways. First, the\ud participants, speaking through the sacred discourse, express an extension to or linkage\ud with the secular literature, revealing much more overlap between the two discourses than\ud was expected. Second, the secular literature does not capture the sacred discourse; there\ud is an appurtenance — an add-on — a more spiritual dimension, to consider

Structure of the Golgi and Distribution of Reporter Molecules at 20°C Reveals the Complexity of the Exit Compartments

Incubating cells at 20°C blocks transport out of the Golgi complex and amplifies the exit compartments. We have used the 20°C block, followed by EM tomography and serial section reconstruction, to study the structure of Golgi exit sites in NRK cells. The dominant feature of Golgi structure in temperature-blocked cells is the presence of large bulging domains on the three trans-most cisternae. These domains extend laterally from the stack and are continuous with “cisternal” domains that maintain normal thickness and alignment with the other stacked Golgi cisternae. The bulging domains do not resemble the perpendicularly extending tubules associated with the trans-cisternae of control cells. Such tubules are completely absent in temperature-blocked cells. The three cisternae with bulging domains can be identified as trans by their association with specialized ER and the presence of clathrin-coated buds on the trans-most cisterna only. Immunogold labeling and immunoblots show a significant degradation of a medial- and a trans-Golgi marker with no evidence for their redistribution within the Golgi or to other organelles. These data suggest that exit from the Golgi occurs directly from three trans-cisternae and that specialized ER plays a significant role in trans-Golgi function

Proteinase-activated receptors (PARs) as targets for antiplatelet therapy

Since the identification of the proteinase-activated receptor (PAR) family as mediators of serine protease activity in the 1990s, there has been tremendous progress in the elucidation of their pathophysiological roles. The development of drugs that target PARs has been the focus of many laboratories for the potential treatment of thrombosis, cancer and other inflammatory diseases. Understanding the mechanisms of PAR activation and G protein signalling pathways evoked in response to the growing list of endogenous proteases has yielded great insight into receptor regulation at the molecular level. This has led to the development of new selective modulators of PAR activity, particularly PAR1. The mixed success of targeting PARs has been best exemplified in the context of inhibiting PAR1 as a new antiplatelet therapy. The development of the competitive PAR1 antagonist, vorapaxar (Zontivity), has clearly shown the value in targeting PAR1 in acute coronary syndrome (ACS); however the severity of associated bleeding with this drug has limited its use in the clinic. Due to the efficacy of thrombin acting via PAR1, strategies to selectively inhibit specific PAR1-mediated G protein signalling pathways or to target the second thrombin platelet receptor, PAR4, are being devised. The rationale behind these alternative approaches is to bias downstream thrombin activity via PARs to allow for inhibition of pro-thrombotic pathways but maintain other pathways that may preserve haemostatic balance and improve bleeding profiles for widespread clinical use. This review summarizes the structural determinants that regulate PARs and the modulators of PAR activity developed to date

Protease-activated receptor 2 : are common functions in glial and immune cells linked to inflammation-related CNS disorders?

Protease-activated receptors (PARs) are a novel family of G-protein coupled receptors (GPCRs) whose activation requires the cleavage of the N-terminus by a serine protease. However recent evidence reveals that alternative routes of activation also occur and that PARs signal via multiple pathways and that pathway activation is activator-dependent. Given our increased understanding of PAR function both under physiological and pathophysiological conditions; one aspect that has remained a constant is the link between PAR2 and inflammation. PAR2 is expressed in immune cells of both the innate and adaptive immune system and has been shown to play a role in several peripheral inflammatory conditions. PAR2 is similarly expressed on astrocytes and microglia within the CNS and its activation is either protective or detrimental to CNS function depending on the conditions or disease state investigated. With a clear similarity between the function of PAR2 on both immune cells and CNS glial cells, here we have reviewed their roles in both these systems. We suggest that the recent development of novel PAR2 modulators, including those that show biased signalling, will further increase our understanding of PAR2 function and the development of potential therapeutics for CNS disorders in which inflammation is proposed to play a role

Preliminary assessment of pre-morbid DNA methylation in individuals at high genetic risk of mood disorders

OBJECTIVES: Accumulating evidence implicates altered DNA methylation in psychiatric disorders, including bipolar disorder (BD) and major depressive disorder (MDD). It is not clear, however, whether these changes are causative or result from illness progression or treatment. To disentangle these possibilities we profiled genome‐wide DNA methylation in well, unrelated individuals at high familial risk of mood disorder. DNA methylation was compared between individuals who subsequently developed BD or MDD [ill later (IL)] and those who remained well [well later (WL)]. METHODS: DNA methylation profiles were obtained from whole‐blood samples from 22 IL and 23 WL individuals using the Infinium HumanMethylation450 BeadChip. Differential methylation was assessed on a single‐locus and regional basis. Pathway analysis was performed to assess enrichment for particular biological processes amongst nominally significantly differentially methylated loci. RESULTS: Although no locus withstood correction for multiple testing, uncorrected P‐values provided suggestive evidence for altered methylation at sites within genes previously implicated in neuropsychiatric conditions, such as Transcription Factor 4 (TCF4) and Interleukin 1 Receptor Accessory Protein‐Like 1 ([IL1RAPL1]; P≤3.11×10(−5)). Pathway analysis revealed significant enrichment for several neurologically relevant pathways and functions, including Nervous System Development and Function and Behavior; these findings withstood multiple testing correction (q≤0.05). Analysis of differentially methylated regions identified several within the major histocompatibility complex (P≤.000 479), a region previously implicated in schizophrenia and BD. CONCLUSIONS: Our data provide provisional evidence for the involvement of altered whole‐blood DNA methylation in neurologically relevant genes in the aetiology of mood disorders. These findings are convergent with the findings of genome‐wide association studies

To Sport Program After Lower Extremity Injury

Introduction 8.6 million sports and recreation related injury episode per year Inadequate rehabilitation and premature return to play identified as risk factors for multiple lower extremity injuries Objective Assess the effectiveness of a return to sport program established for patients with lower extremity injuries. Methods Outcome Measures: IKDC, TSK-11 Performance based tests for pre and post assessment: Single leg timed hop, triple crossover hop Results Statistically significant changes from pre- to post-ASCEND in: 6 meter single-leg timed hop, triple crossover hop, IKDC, TSK-11 Conclusion The ASCEND return to sport program elicits statistically significant change in single leg timed hop, triple crossover hop, IKDC, and TSK-11. Clinical Relevance A high density return to sport program can elicit change through agility, plyometrics, strength, core, and endurance training

Golgi Structure in Three Dimensions: Functional Insights from the Normal Rat Kidney Cell

Three-dimensional reconstructions of portions of the Golgi complex from cryofixed, freeze-substituted normal rat kidney cells have been made by dual-axis, high-voltage EM tomography at ∼7-nm resolution. The reconstruction shown here (∼1 × 1 × 4 μm3) contains two stacks of seven cisternae separated by a noncompact region across which bridges connect some cisternae at equivalent levels, but none at nonequivalent levels. The rest of the noncompact region is filled with both vesicles and polymorphic membranous elements. All cisternae are fenestrated and display coated buds. They all have about the same surface area, but they differ in volume by as much as 50%. The trans-most cisterna produces exclusively clathrin-coated buds, whereas the others display only nonclathrin coated buds. This finding challenges traditional views of where sorting occurs within the Golgi complex. Tubules with budding profiles extend from the margins of both cis and trans cisternae. They pass beyond neighboring cisternae, suggesting that these tubules contribute to traffic to and/or from the Golgi. Vesicle-filled “wells” open to both the cis and lateral sides of the stacks. The stacks of cisternae are positioned between two types of ER, cis and trans. The cis ER lies adjacent to the ER-Golgi intermediate compartment, which consists of discrete polymorphic membranous elements layered in front of the cis-most Golgi cisterna. The extensive trans ER forms close contacts with the two trans-most cisternae; this apposition may permit direct transfer of lipids between ER and Golgi membranes. Within 0.2 μm of the cisternae studied, there are 394 vesicles (8 clathrin coated, 190 nonclathrin coated, and 196 noncoated), indicating considerable vesicular traffic in this Golgi region. Our data place structural constraints on models of trafficking to, through, and from the Golgi complex

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology

Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes