Fescue toxicosis can produce negative effects on animal weight gain and physiology. Sixty-four steers were grazed on endophyte-infected (E+) KY-31 tall fescue for 77 days in 2007 and sixty steers grazed for 86 days in 2008 to evaluate interactions with implantation of steroidal implants and concentrate feeding on performance and physiology of yearling steers. Steers were stratified by body weight for assignment to six, 3.0-ha toxic tall fescue pastures. The main plot treatment of with or without pelleted soybean hulls (SBH) were randomly assigned to pastures. Pelleted SBH were group-fed to provide daily consumptions of 2.3 kg/steer/d (as fed). Sub-plot treatments of with or without ear implantation with steroid hormone (200 mg progesterone--20 mg estradiol were assigned to groups of five or six steers within each pasture. Average daily gain in the experiment showed an additive effect of feeding SBH and implanting (P

Androgens are the main regulators of human hair growth stimulating larger, terminal hair development e.g. beard and causing scalp balding, androgenetic alopecia. Hair disorders cause psychological distress but are poorly controlled. Androgens probably act by altering regulatory paracrine factors produced by the mesenchyme-derived dermal papilla. This study aimed to investigate paracrine factors involved in androgen-regulated alopecia, particularly hepatocyte growth factor (HGF) family members, by investigating their in vivo status. Balding and non-balding scalp hair follicles and their component tissues were isolated and analysed by molecular biological methods (reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative PCR and DNA microarray analysis), cell culture and immunohistochemistry. Scalp follicles expressed a range of paracrine messenger genes. The dermal papilla, cultured dermal papilla cells and dermal sheath expressed several HGF family genes, while matrix cells only produced the receptor RON suggesting autocrine roles for HGF and MSP, but a paracrine route only for MSP. Comparing balding and non-balding follicles from the same individuals revealed the expected reduction in several keratin and keratin-related protein genes supporting this approach's validity. There were also significant differences in paracrine factors previously implicated in androgen action by in vitro studies. Several factors believed to increase during androgen stimulation of larger, darker follicles, e.g. IGF-I and SCF, were lowered in balding follicles, while putative inhibitory factors, e.g. TGFß-1, were increased. HGF and MSP and their receptors, c-Met and RON, were significantly reduced. These results increase our understanding of androgen action in human hair follicles; this could lead to better treatments for hair disorders.

Hair growth disorders cause significant psychological distress, but are poorly controlled. Since prostaglandin F₂α (PGF₂α) and prostamide F₂α analogue glaucoma treatments cause eyelash growth as side-effects, they may be useful for alopecia. How they function is unknown; possibilities include direct action on hair follicles or stimulating follicular blood flow. It is important to clarify whether scalp follicles can also respond as human follicle response to androgens differ with body site. Therefore, human scalp follicles were grown in vitro in organ culture with PGF₂α, latanoprost, a PGF₂α analogue, and bimatoprost, a prostamide F₂α analogue, with, or without, appropriate antagonists, and the presence of PGF₂α (FP) and prostamide F₂α receptors were investigated using molecular biological and immunohiostochemical methods. Each treatment significantly stimulated follicle growth rate, the percentage of growing follicles, and the amount of hair produced in a dose-responsive manner (10nM-1μM); the receptor antagonists blocked these effects. Immunohistochemistry of frozen scalp sections demonstrated FP protein only in dermal papillae and connective tissue sheaths. RT-PCR identified FP and various prostamide F₂α receptors in anagen follicles and isolated dermal papillae and bulbar connective tissue sheath, but not in bulb matrix or other epithelial tissues. Therefore, isolated human scalp hair follicles can respond biologically to PGF₂α and related pharmaceuticals in organ culture via follicular receptors and express the genes and protein for FP and prostamide F₂α receptors. PGF₂α-related drugs appear to act directly on follicles via receptors in the regulatory dermal papilla. They offer an exciting, novel approach for treating alopecia and merit clinical investigation.

The emotions associated with initiating, maintaining, and reinforcing hairpulling disorder (trichotillomania) were studied. Studies conducted have only looked at small community or inpatient samples, and little is known about the interplay of hairpulling subtypes and emotions. For this study, 427 participants completed an online questionnaire around their hairpulling subtype, severity, emotions experienced by hairpulling, and comorbid anxiety and depression. Using the Milwaukee Inventory for Subtypes of Trichotillomania-Adult Version (MIST-A; Flessner, Woods, Franklin, Cashin, & Keuthen, 2008), this is the first study to address the regulation of emotions across subtypes. Participants were divided as either high- or low-focused and either high- or low automatic. Significant differences between hairpulling subtypes and hairpulling severity were reported. Subtypes differed in the severity they experienced emotions; individuals with high-focused pulling reported more intense negative emotions, and a greater number of emotions regulated by pulling. Positive emotions⎯happiness, relief, and calm⎯were also found to play a significant role in reinforcing hairpulling. For high-focused subtypes, negative emotions before- and after-pulling were associated with greater severity, indicating that altering negative emotions via pulling plays an important role for high-focused subtypes. High-focused subtypes also reported higher stress, depression and anxiety than either automatic subtypes or the general population, and were found to have anxiety and depression significantly associated with hairpulling severity and experiencing negative emotions that initiated hairpulling. Clinical and treatment implications, study limitations, and areas of future research are discussed / xviii, 227 leaves ; 29 cm

The melanocortin-1 receptor (MC1R) is a G-protein coupled receptor (GPCR) expressed on the surface of the melanocyte. MC1R activation after UV exposure results in the production of the dark eumelanin pigment and the tanning process in humans, providing protection from UV induced DNA damage. MC1R activation has also recently been linked to DNA repair. The MC1R gene is highly polymorphic in Caucasian populations with a number of MC1R variant alleles associated with red hair, fair skin, poor tanning and increased risk of melanoma and non-melanoma skin cancer. These MC1R variant receptors were thought to be loss of function, however the type of defect and the extent of the loss of function for individual variants was relatively unknown before the commencement of this PhD project. Many GPCR mutant proteins are intracellularly retained, resulting in a loss of signalling ability. To determine if this was the case for MC1R variant receptors, the localisation of the wild type and variant MC1R protein was investigated using immunofluorescence and radio-ligand binding on transfected melanocytic cells as well as primary melanocyte strains. For the first time, several MC1R variants including V60L, R151C, I155T, R160W and R163Q, were shown to have reduced cell surface expression compared to wild type MC1R. cAMP assays were used to determine the signalling ability of activated wild type and variant MC1R, importantly, variant receptors with reduced cell surface expression showed corresponding impairment in cAMP signalling. In contrast, the R142H and D294H variants, which have normal cell surface expression but significantly impaired cAMP signalling, are thought to have a defect in G-protein coupling. Some MC1R variants were found to have dominant negative activity on the wild type receptor in co-expression studies, this result may explain the MC1R heterozygote effect on human pigmentation phenotypes. This dominant negative effect resulted in either reduced wild type cell surface expression or reduced G-protein coupling and may be mediated by receptor dimerisation. In order to validate the in vitro studies, comparison of variant receptor characteristics with skin and hair colour data of individuals both homozygous and heterozygous for MC1R variant alleles was performed. This revealed parallels between variant MC1R cell surface expression, functional ability, dominant negative activity and the strength of the effects of variant alleles on human pigmentation. From the in vitro functional studies, it was clear that most variant receptors retained some signaling ability, although the relative abilities varied. An important unanswered question in the literature was whether the phenotype of carriers of the high penetrance MC1R variant alleles was actually representative of complete loss of function for MC1R. Due to the rarity of MC1R null alleles they had only previously been found in the heterozygous state, however we described the phenotype of one individual compound heterozygous for two frameshift mutations resulting in an individual unable to produce any functional MC1R protein. Phenotypic analysis indicated that red hair and fair skin is found in the absence of MC1R. Finally, preliminary studies using low temperature, chemical or pharmacological chaperones indicated that the cell surface expression of some MC1R variants could be rescued in cell transfection experiments. This resulted in a restoration of signaling ability after stimulation with agonist. These studies into the localization and function of MC1R variants have contributed to a greater understanding of the molecular mechanism underlying the association of MC1R with skin cancer risk phenotypes, and may lead to future drug based therapies that are able to rescue the function of MC1R variants that are intracellularly retained.

Primary wool follicles are initiated in the skin of sheep foetuses at approximately day 50 of gestation as the result of complex reciprocal molecular interactions between the mesenchyme and overlying epithelium. The lifetime wool production potential and fibre diameter of the Merino sheep is dependent on the total number of follicles initiated in utero. Understanding the molecular events that surround primary wool follicle initiation may provide approaches to enhance or manipulate this process in order to maximise the profitability of wool production enterprises. In order to study the morphological and molecular changes occurring during early wool follicle development, a foetal skin series spanning primary follicle initiation was generated. Foetal skin was sampled from the shoulder, midside and rump of four foetuses at 8 time points between day 43 and day 68 of gestation. Histological characterisation of the shoulder skin samples revealed that primary epidermal placodes emerged at around day 53, dermal condensates were visible from day 57 and downgrowth of the follicle began at day 68. An equation relating age of the foetus (day of gestation post AI) and crown-rump length, specific to Merino foetuses, was developed for use in future studies of this nature. Molecular markers of fibroblast migration, epidermal and dermal stem cells and cell proliferation were selected to test the hypothesis that dermal condensates are initiated at discrete sites beneath the epidermis as a result of a combination of migration and arrangement of multipotent pre-papilla cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis of RAC1 and RHOa (migration markers), β1-integrin and alkaline phosphatase (stem cell markers), proliferative nuclear cell antigen and cyclinB1 (proliferation markers), patched-1, selected tumor necrosis factor (TNF) signalling molecules and eleven reference genes was conducted using midside and rump skin samples from each of four foetuses from the 8 time points. geNorm analysis of the reference and target genes revealed that the migration markers RAC1 and RHOa along with GAPDH were the most stably expressed genes in this sample series. Significant changes in mRNA expression were detected for β1-integrin, alkaline phosphatase, patched-1 and the TNF members EDA, EDAR, TROY and TRAF6. Many of these significant differences in expression coincided with key morphological events. Significant differences in expression were also detected between the midside and rump samples for numerous transcripts. Laser capture microdissection (LCM) was implemented for analysis of the target transcripts within particular structures of foetal sheep skin. Frozen tissue sectioning, staining, LCM, RNA extraction and cDNA synthesis were optimised for qRT-PCR analysis of endogenous controls and selected TNF transcripts. Several RNA extraction methods and reverse transcription approaches were trialled to ensure optimum extraction and reverse transcription efficiency for this tissue type. Exogenous mRNA transcripts were also incorporated prior to RNA extraction and reverse transcription to track reaction efficiency between samples. A comparison of different slide types revealed that laser pressure catapulting from membrane slides was an absolute requirement for foetal skin tissue studies. Follicle regions (including the epidermal placode and dermal condensate) and the adjacent non-follicle regions were laser captured from foetal skin, and the mRNA expression levels of patched-1 and selected TNF members was compared. Preliminary qRT-PCR analysis using this technique revealed that EDAR, TROY and PTCH1 mRNA levels were higher in the follicle regions than the non-follicle regions. The TNF signalling pathway appears to play an important role in primary wool follicle initiation and patterning at different sites on the body. Spatial differences in expression of some of these regulators may be involved in initiating different types of follicles. The molecular events surrounding primary wool follicle initiation also show a high degree of conservation between sheep, humans, and mice. Considering the high degree of DNA sequence conservation as well as the histological, signalling and cycling similarities between sheep and humans, sheep may represent a better model for the study of human hair follicle initiation and disease than the currently used mice and rat models. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1523639 / Thesis (Ph.D.) -- University of Adelaide, School of Agriculture, Food and Wine, 2010

The cochlea is an organ which extracts frequency information from the input sound wave. It also produces nerve signals, which are further analysed by the brain and ultimately lead to perception of the sound. An existing model of the cochlea by Fragni`ere is first analysed by simulation. This passive model is found to have the properties that the living cochlea does in terms of the frequency response. An analog VLSI circuit implementation of this cochlear model in CMOS weak inversion is proposed, using log-domain filters in current domain. It is fabricated on a chip and a measurement of a basilar membrane section is performed. The measurement shows a reasonable agreement to the model. However, the circuit is found to have a problem related to transistor mismatch, causing different behaviour in identical circuit blocks. An active cochlear model is proposed to overcome this problem. The model incorporates the effect of the outer hair cells in the living cochlea, which controls the quality factor of the basilar membrane filters. The outer hair cells are incorporated as an extra voltage source in series with the basilar membrane resonator. Its value saturates as the input signal becomes larger, making the behaviour rather closer to that of a passive model. The simulation results show this nonlinear phenomenon, which is also seen in the living cochlea. The contribution of this thesis is summarised as follows: a) the first CMOS weak inversion current domain basilar membrane resonator is designed and fabricated, and b) the first active two-dimensional cochlear model for analog VLSI implementation is developed.

Thesis (M.A.)--Eastern Illinois University, 2008. / Includes bibliographical references (leaves 77-84).

Thesis (PhD) -- University of Western Sydney, Nepean, 1997. / Thesis submitted under the University of Western Sydney, Nepean-CSIRO postgraduate scholarship program. Bibliography : leaves 167-190.

Thesis (M.A.)--Georgia State University, 2007. / Title from file title page. Cassandra White, committee chair; Emanuela Guano, Megan Sinnott, committee members. Electronic text (130 p.) : digital, PDF file. Description based on contents viewed June 6, 2008. Includes bibliographical references (p. 117-123).