Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation

Thesis (M.A.)Systemic sclerosis (SSc) is a clinically heterogenous chronic fibrotic disease which affects skin and internal organs. While the pathogenesis of SSc remains unknown, the hallmark of both localized and diffuse SSc in the skin is the replacement of normal dermal architecture with excessive deposition of collagen and other connective tissue macromolecules. Progressive replacement of tissue architecture by collagen-rich extracellular matrix (ECM) results in functional impairment of affected organs. Fibrotic damage to these affected organs accounts for much of the morbidity and mortality concomitant with SSc, particularly in the lungs. Myofibroblasts are the primary ECM-secreting cells during wound healing and fibrosis. Myocardin-related transcription factor A (MRTF-A), is an important regulator of myofibroblast differentiation, depending on serum response factor (SRF) for smooth muscle actin (SMA) and Sp1 in the regulation of collagen gene expression. MRTF-A continually shuttles between the nucleus and cytoplasm in unstimulated cells. Signals of stress, mechanical force, and migration control MRTF-A movement by a mechanism in which Rho-activated cytoskeletal actin polymerization induces its relocation from the cytoplasm to the nucleus. The major hypothesis in this thesis is that MRTF-A is dysregulated (impairment of a physiological regulatory mechanisms) and/or activated in SSc patients in part through transforming growth factor beta (TGF-β). To test this hypothesis, immunohistochemistry using MRTF-A antibodies was performed on SSc patient skin lesions and healthy control skin. Staining was observed in the epidermis, epidermal structures, vasculature and dermis of SSc and healthy control skin. In the epidermal layer of patients with SSc, there was significantly more nuclear localization of MRTF-A then in normal controls. Prominent staining is also present in endothelial, perivascular and some perivascular inflammatory cells of SSc patients. Perivascular staining was not seen in healthy controls. Interestingly, there was some accumulation of nuclear MRTF-A in areas typical of myofibroblasts in SSc skin, but this staining is not as striking as vascular staining. TGF-β activates MRTF-A in a cell-specific manner. As SSc typically begins within the skin, human dermal fibroblasts (HDF) were grown in culture. HDFs synthesize and secrete collagen to a greater extent when compared to human lung fibroblasts (IMR90 cells). Treatment with TGF-β enhances cytoplasmic localization of MRTF-A at 4-8 hours in HDFs and prolongs nuclear localization. Transgenic mouse lung cells were isolated from an MRTF-A loss-of-function mouse carrying the 3.6 kb proximal promoter of the rat COL1A1 gene driving topaz green fluorescent protein (GFP) (pOB3.6COLGFPtpz). Since angiotensin II (ANG II) may enhance TGF-β response or collagen transcription directly, wild type (WT) and MRTF-A knockout (KO) cells were treated with ANG II and TGF-β. Quantification of collagen transcription by GFP fluorescence and protein synthesis by Western and secretion by Sircol analysis revealed collagen gene expression is consistently lower in KO fibroblasts compared to WT. Total percentage of fluorescent KO cells were consistently lower in comparison to WT cells as well. KO cells do not respond to TGF-β or ANG II treatment, whereas TGF-β increased collagen gene expression by WT cells, but not KO cells. Furthermore, treatment with ANG II did not up-regulate transcription in WT mouse lung fibroblasts. However, TGF-β receptor kinase 1 (TβR-1) inhibitor SB431542 attenuated collagen transcription in both WT and KO fibroblasts regardless of treatment suggesting that the receptor is active with or without MRTF-A possibly with an endogenous ligand produced by these cells. The activation of MRTF-A is an important protein regulating collagen synthesis and may potentially serve as a therapeutic target in future treatments of fibrotic disease such as SSc

Household Technology and the Division of Household Labor in Utah Families

The purpose of this study was to examine the relationship of household appliances and the division of labor in accomplishing household tasks in the family. It investigated the relationship between ownership of specific items of household equipment and the performance of directly related household tasks and the overall ownership of household equipment and the overall division of labor in the family. Data for this study came from Determinants and outcomes of Household Time Use, which is part of the S-206 Regional Research Project. Data from 214 two-parent, two-child households were analyzed to determine the relationship between ownership of household equipment and time spent in three categories of household tasks by husbands, wives and children. Ownership of household equipment was determined by means of an equipment inventory. The ownership of appliances and their relationship to the performance of directly associated tasks included: (microwave oven and time spent in food preparation; (2) dishwasher and garbage disposal and time spent in dishwashing; and (3) power garden and/or yard equipment and power shop tools and time spent in maintenance of home, yard, car, and pets. The total time spent in household production by husbands, wives, children and its relationship to the total number of household appliances owned was also studied. The t-test, analysis of variance (ANOVA) and Kruskal-Wallis were used to analyze the differences in proportion of time spent in the various household tasks by wives, husbands, and children by ownership of related household equipment. No significant differences were found in the proportion of time spent in food preparation, dishwashing, and maintenance by wives, husbands, and children in households that did and did not own the related household equipment. The correlation between level of equipment ownership and husbands\u27 and children\u27s proportion of total family time spent in household work was not significant indicating that as more equipment is acquired husbands and children do not contribute a smaller proportion of total family time in household work

Updated high-resolution grids of monthly climatic observations - the CRU TS3.10 Dataset

This paper describes the construction of an updated gridded climate dataset (referred to as CRU TS3.10) from monthly observations at meteorological stations across the world's land areas. Station anomalies (from 1961 to 1990 means) were interpolated into 0.5° latitude/longitude grid cells covering the global land surface (excluding Antarctica), and combined with an existing climatology to obtain absolute monthly values. The dataset includes six mostly independent climate variables (mean temperature, diurnal temperature range, precipitation, wet-day frequency, vapour pressure and cloud cover). Maximum and minimum temperatures have been arithmetically derived from these. Secondary variables (frost day frequency and potential evapotranspiration) have been estimated from the six primary variables using well-known formulae. Time series for hemispheric averages and 20 large sub-continental scale regions were calculated (for mean, maximum and minimum temperature and precipitation totals) and compared to a number of similar gridded products. The new dataset compares very favourably, with the major deviations mostly in regions and/or time periods with sparser observational data. CRU TS3.10 includes diagnostics associated with each interpolated value that indicates the number of stations used in the interpolation, allowing determination of the reliability of values in an objective way. This gridded product will be publicly available, including the input station series (http://www.cru.uea.ac.uk/ and http://badc.nerc.ac.uk/data/cru/)

Clover Trapping Mule Deer in Northwest Montana: Lessons Learned in a Unique Environment

Mule deer (Odocoileus hemionus) populations are in decline in many parts of western Montana, and in 2017, harvest in Montana Fish Wildlife and Parks (MFWP) management region 1 (R1) reached an all-time low. This prompts a need to better understand mule deer habitat selection behaviors in a range of ecosystems. Using resource selection functions (RSFs), we will compare how GPS-collared mule deer select nutritional resources and hiding cover at large scales (home range level) and fine scales (within-home ranges) relative to forage quality in 3 distinct ecosystems throughout western Montana. In February of 2017, we successfully captured 30 mule deer does along the Rocky Mountain Front using helicopternet-gunning, but were unsuccessful in the Whitefish Range and Fisher River drainage of R1 due to dense canopy cover. From December 2017 to present, we have relied on a crew of graduate students, MFWP game wardens and biologists, technicians, volunteers, and private citizens to scout for and clover-trap mule deer in R1. Here we present our capture success rate thus far, though trapping efforts are ongoing. We wish highlight how creative methods and recruitment of help from across a state agency can be pooled to initiate rigorous research in a thickly forested environment on a scarcely seen ungulate

Hip Strength and Core Endurance in Female Adolescent Runners With and Without Knee Pain

BACKGROUND AND PURPOSE: Patellofemoral pain syndrome (PFPS) is one of the most prevalent orthopedic conditions affecting young athletes today. Epidemiological studies have reported PFPS to be the most common injury seen in runners. Deficits in hip strength have been identified in runners with PFPS, but core endurance in relation to knee pain has not been well documented. The primary purpose of our study was to investigate differences in hip strength and core endurance between female, adolescent runners with PFPS and their age matched controls. The secondary purpose of our research was to examine any correlations between hip strength and core endurance in our participants. METHODS: A cross sectional design was used. We recorded pain, Kujala score, hip strength and endurance and core endurance in 34 adolescent female cross country runners. Cases with PFPS were defined as young female runners with a minimum three month history of anterior knee pain of insidious onset and had a most severe knee pain rated 3/10 or higher. Control subjects had no history of knee surgery, traumatic knee injuries, patellar instability, or neurologic conditions. Between-group differences and correlations were calculated between age-matched cases and controls using t-tests. Pearson correlation coefficients were used to determine associations for selected measures. RESULTS: No significant differences were observed between cases and controls for hip strength and endurance. However, there was a large percent difference between cases and controls in selected core endurance measures. It was found that all hip strength and core endurance results had low correlations ( \u3c 0.28). Among cases with PFPS, a strong and significant, negative correlation was found between subjects’ reported worst pain and Kujala score (r=-0.79, p\u3c0.05)). A non-significant moderate negative correlation between side plank endurance and usual pain was found (r=-0.49). CONCLUSION: There were minimal differences noted in isometric strength tests between groups. There was a clear difference noted with endurance testing between groups. However, this difference was not found to be significant, which could be due to low number of subjects with PFPS. The differences in endurance between athletes with PFPS and their pain free counterparts merit further investigation and research. Of note, it was found that strength and endurance had a minimal correlation; this indicates that clinically, endurance cannot be inferred from isometric strength testing. Therefore, we recommend clinicians perform specific measures of endurance when attempting to identify impairments in runners with PFPS

Using \u3cem\u3eLearning Express-Ways\u3c/em\u3e in Special Education Teacher Preparation: Developing Student-Faculty Relationships as a Path to Partnership

This paper explores the effects of implementing Learning Express-Ways as an instructional communication tool between students and faculty in courses that are part of a special education teacher preparation program and apprenticeship. Findings suggest that using Learning Express-Ways contributed to the development of learning relationships with faculty and this instructional communication tool may be helpful in creating a partnership-focused approach in special education teacher preparation program

Magnetically filtered Faraday probe for measuring the ion current density profile of a Hall thruster

The ability of a magnetically filtered Faraday probe (MFFP) to obtain the ion current density profile of a Hall thruster is investigated. The MFFP is designed to eliminate the collection of low-energy, charge-exchange (CEX) ions by using a variable magnetic field as an ion filter. In this study, a MFFP, Faraday probe with a reduced acceptance angle (BFP), and nude Faraday probe are used to measure the ion current density profile of a 5 kW5kW Hall thruster operating over the range of 300–500 V300–500V and 5–10 mg/s5–10mg∕s. The probes are evaluated on a xenon propellant Hall thruster in the University of Michigan Large Vacuum Test Facility at operating pressures within the range of 4.4×10−4 Pa4.4×10−4Pa Xe (3.3×10−6 Torr3.3×10−6Torr Xe) to 1.1×10−3 Pa1.1×10−3Pa Xe (8.4×10−6 Torr8.4×10−6Torr Xe) in order to study the ability of the Faraday probe designs to filter out CEX ions. Detailed examination of the results shows that the nude probe measures a greater ion current density profile than both the MFFP and BFP over the range of angular positions investigated for each operating condition. The differences between the current density profiles obtained by each probe are attributed to the ion filtering systems employed. Analysis of the results shows that the MFFP, operating at a +5 A+5A solenoid current, provides the best agreement with flight-test data and across operating pressures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87898/2/013503_1.pd

Planning guidelines for koala conservation and recovery: A guide to best planning practice

The information contained in the guide is a synthesis of four years research into the conservation and restoration of koala populations in fragmented landscapes of eastern Australia. The guidelines also capture a decade of practical research and planning experience by the Australian Koala Foundation in mapping koala habitat and developing koala conservation and management plans for local government areas in New South Wales. They draw on the collective knowledge of researchers who wanted to see their results put into action with practical outcomes for koala conservation