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No / Senile graying of human hair has been the subject of intense research since ancient times. Reactive oxygen species have been implicated in hair follicle melanocyte apoptosis and DNA damage. Here we show for the first time by FT-Raman spectroscopy in vivo that human gray/white scalp hair shafts accumulate hydrogen peroxide (H(2)O(2)) in millimolar concentrations. Moreover, we demonstrate almost absent catalase and methionine sulfoxide reductase A and B protein expression via immunofluorescence and Western blot in association with a functional loss of methionine sulfoxide (Met-S=O) repair in the entire gray hair follicle. Accordingly, Met-S=O formation of Met residues, including Met 374 in the active site of tyrosinase, the key enzyme in melanogenesis, limits enzyme functionality, as evidenced by FT-Raman spectroscopy, computer simulation, and enzyme kinetics, which leads to gradual loss of hair color. Notably, under in vitro conditions, Met oxidation can be prevented by L-methionine. In summary, our data feed the long-voiced, but insufficiently proven, concept of H(2)O(2)-induced oxidative damage in the entire human hair follicle, inclusive of the hair shaft, as a key element in senile hair graying, which does not exclusively affect follicle melanocytes. This new insight could open new strategies for intervention and reversal of the hair graying process.

Published Article / This exploratory study employed mainly quantitative and some elements of qualitative methods to analyse interview data emerged from both informal interviews and questionnaire on 280 salon operators. This study focused on the educational background of the owners of smaller businesses as a factor related to the engagement in the marketing research within hair salon business in Dr. R.S Mompati district in the North-West Province of South Africa. The findings revealed that even though majority of the operators did not engage in marketing research, those who collected information on certain marketing research activities may have been influenced by their educational background. Thus it is postulated that the higher the educational background, the more likely it is that hair salons conduct marketing research. The author discusses the implication of the findings for smaller businesses to engage in marketing research, the value of the study, recommendation for further research and limitations of the study.

The hair follicle (HF) is a cyclic biological system that progresses through stages of growth, regression and quiescence, each being characterized by unique patterns of gene activation and silencing. MicroRNAs (miRNAs) are critically important for gene silencing and delineating their role in hair cycle may provide new insights into mechanisms of hair growth control and epithelial tissue remodelling. The aims of this study were: 1) To define changes in the miRNA profiles in skin during hair cycle-associated tissue remodelling; 2) To determine the role of individual miRNAs in regulating gene expression programs that drive HF growth, involution and quiescence; 3) and to explore the role of miRNAs in mediating the effects of BMP signalling in the skin. To address Aims 1 & 2, global miRNA expression profiling in the skin was performed and revealed marked changes in miRNAs expression during distinct stages of the murine hair cycle. Specifically, miR-31 markedly increased during anagen and decreased during catagen and telogen. Administration of antisense miR-31 inhibitor into mouse skin during the early- and mid-anagen phases of the hair cycle resulted in accelerated anagen development, and altered differentiation of hair matrix keratinocytes and hair shaft formation. Microarray, qRT-PCR and Western blot analyses revealed that miR-31 negatively regulates expression of Fgf10, the components of Wnt and BMP signalling pathways Sclerostin and BAMBI, and Dlx3 transcription factor, as well as selected keratin genes. Luciferase reporter assay revealed that Krt16, Krt17, Dlx3, and Fgf10 serve as direct miR-31 targets. In addition, miR-214 was identified as a potent inhibitor of the Wnt signalling pathway in the keratinocytes. Mutually exclusive expression patterns of miR-214 and β-catenin was observed during HF morphogenesis. MiR-214 decreases the expression of β-catenin and other components of Wnt signalling pathways c-myc, cyclin D1, and Pten in the keratinocytes. Luciferase reporter assay proved that β-catenin serves as a direct target of miR-214. In addition, miR-214 prevented translocation of β-catenin into the nucleus in response to the treatment with an activator of the Wnt signalling pathway lithium chloride, and abrogated the lithium-induced increase of the expression of the Wnt target gene VI Axin2. This suggests that miR-214 may indeed be involved in regulation of skin development and regeneration at least in part, by controlling the expression of β-catenin and the activity of the Wnt signalling pathway. To address Aim 3, the role of miRNAs in mediating the effects of the bone morphogenetic protein (BMP) signalling in the skin was explored. MiRNAs were isolated from the primary mouse keratinocytes treated with BMP4 and processed for analysis of global miRNA expression using the microarray approach. Microarray and real-time PCR analysis revealed BMP4-dependent changes in the expression of distinct miRNAs, including miR-21, which expression was strongly decreased in the keratinocytes after BMP4 treatment. In contrast, miR-21 expression was substantially higher in the skin of transgenic mice over-expressing BMP antagonist Noggin. Transfection of the keratinocytes with miR-21 mimic revealed existence of two groups of the BMP target genes, which are differentially regulated by miR-21. Thus, this suggests a novel mechanism controlling the effects of BMP signalling in the keratinocytes. Thus, miRNAs play important roles in regulating gene expression programs in the skin during hair cycle. By targeting a number of growth regulatory molecules, transcription factors and cytoskeletal proteins, miRNAs are involved in establishing an optimal balance of gene expression in the keratinocytes required for the HF and skin homeostasis.

Determining the postmortem interval (PMI) remains one of the most important but challenging factors to establish in a suspicious death investigation. Unfortunately, as time passes current methods lose accuracy and only allow investigators to approximate how long ago death occurred. Bodies interred in clandestine graves prove particularly challenging due to an abundance of variables that need to be taken into consideration. Due to the problems associated with determining the PMI of buried remains this study will utilise macroscopic, microscopic, molecular, chemical and microbiological analyses to systematically document the decompositional changes to human hair and porcine cartilage and bone in a burial environment. The aim was to correlate decompositional changes with time and develop new methods for estimating the PMI of remains found in this context. Whole trotters (from which the cartilage was harvested) exhibited decompositional changes including darkening of the dermis, skin slippage, liquefaction of soft tissues and complete skeletonisation. The decompositional changes to cartilage included a loss of cartilage covering articular facets, changes in colour and texture, formation of orthorhombic crystals, a change in surface pH and colonisation by bacteria. The bacteria found on the cartilage surface were in close proximity to the crystals and when cultured on a B-41 medium were found to precipitate crystals of the same morphology and chemical composition to those found on the cartilage surface. Three species of bacteria (Acinetobacter calcoaceticus, Acinetobacter iwoffii and Grimontia hollisae) were identified based on gas chromatography–mass spectrometry (GC-MS) of their fatty acids and one species (Comamonas sp.) was identified by DNA analysis. Formation of crystals on goat and cow cartilage proved that this was not a porcine specific phenomenon. Human hair exhibited a gradual degradation over time but this was dependent on the characteristics of the burial environment. Decompositional changes included colonisation by fungi, erosions to the cortical surface and formation of tunnels and breaks to the hair shaft. Two fungal species (Aspergillus fumigatus and Penicillium sp.) were identified based on DNA analysis of fungal ribosomal (rDNA) internally transcribed spacer (ITS) regions. The Penicillium sp. was linked with fungal tunnelling of hair. Bone exhibited little modification over time but changes were observed. These included a change in colour of the cortical surface, a change in colour and gradual loss of bone marrow and erosions, cracking and flaking of the cortical bone. Fungi were found to colonise both the bone marrow and bone surface. Whole piglets were buried to document the time period taken to reach skeletonisation. This data was used as a correction factor and combined with the bone results to give an overall time period for the decomposition changes observed. The results of this study suggest that the decompositional changes to cartilage could be used to determine the postmortem interval of buried remains. However, the degradation of hair and bone was too variable to be of use in this context.

The eATP pathway begins a cascade of events which includes the involvement of nitric oxide synthase (NOS) and nitrate reductase (NR) in the production of nitric oxide (NO). Research has shown that SNAP (S-nitroso-N-acetylpenicillamine) and NONOates (diazeniumdiolates) promote the availability of NO and, with the addition of guanylate cyclase, form cyclic guanine monophosphate (cGMP), and root hair growth is promoted. Phosphodiesterases (PDE) break down the cGMP and agents such as IBMX and Viagra inhibit the PDEs thereby inhibiting root hair growth. Several questions remain to be answered. How much cGMP is necessary for the promotion of root hair growth? Is there an optimal concentration of cGMP which stimulates root hair growth, above which is inhibitory, or below which is ineffective? Is there a “non-hydrolyzable analog” of cGMP which is more effective at promoting root hair growth? Is it possible to see inhibition of root hair growth with exposure to a known inhibitor, such as ATPγS, and then reverse the inhibition with a “non-hydrolyzable analog” of cGMP? Answering these vi questions is the substance of this research and the answers will provide direction and understanding to the growth-promoting and regulatory role eATP plays in signal transduction pathways in plants. With the hypothesis asking whether the effects of NO on root hair growth is cGMP-dependent or cGMP-independent we found that there is no consistent concentration of non-hydrolyzable cGMP analog which promotes root hair growth. Additionally we found that the 8-Br-cGMP analog promotes root hair growth more consistently in Arabidopsis thaliana than its counterpart, dibutyryl cGMP. We substantiated previously published results showing an inhibition of root hair growth when root hairs were exposed to high concentrations of ATPγS. Based on these results we believe the promotion of root hair growth in Arabidopsis thaliana to be mediated independently of cGMP. / text

Cognitive impairment in coronary artery disease (CAD) patients can predict poorer quality of life, dementia, and increased mortality. This study aimed to determine the association between long-term cortisol elevations and cognitive function in CAD patients. Participants were recruited at the beginning of a 1 year cardiac rehabilitation program and followed forward. Composite Z-scores were computed from tests measuring memory and executive function at baseline and 1 year. Cortisol deposition (3 months) was measured from a 20 mg, 3 cm hair sample. Analyses of covariance showed less improvement in memory function (F1,50=4.721, p=0.035) but not executive function (F1,49=0.318, p=0.575) in patients dichotomized into a high cortisol group based on a previously established reference range. Prolonged cortisol elevation may be associated with cognitive changes in subjects with CAD.

Cognitive impairment in coronary artery disease (CAD) patients can predict poorer quality of life, dementia, and increased mortality. This study aimed to determine the association between long-term cortisol elevations and cognitive function in CAD patients. Participants were recruited at the beginning of a 1 year cardiac rehabilitation program and followed forward. Composite Z-scores were computed from tests measuring memory and executive function at baseline and 1 year. Cortisol deposition (3 months) was measured from a 20 mg, 3 cm hair sample. Analyses of covariance showed less improvement in memory function (F1,50=4.721, p=0.035) but not executive function (F1,49=0.318, p=0.575) in patients dichotomized into a high cortisol group based on a previously established reference range. Prolonged cortisol elevation may be associated with cognitive changes in subjects with CAD.

<p>Robust regulation of spindle orientation is essential for driving asymmetric cell divisions (ACDs), which generate cellular diversity within a tissue. During the development of the multilayered mammalian epidermis, mitotic spindle orientation in the proliferative basal cells is crucial not only for dictating daughter cell fate but also for initiating stratification of the entire tissue. A conserved protein complex, including LGN, Nuclear mitotic apparatus (NuMA) and dynein/dynactin, plays a key role in establishing proper spindle orientation during ACDs. Two of these proteins, NuMA and dynein, interact directly with astral microtubules (MTs) that emanate from the mitotic spindle. While the contribution of these MT-binding interactions to spindle orientation remains unclear, these implicate apical NuMA and dynein as strong candidates for the machinery required to transduce pulling forces onto the spindle to drive perpendicular spindle orientation. </p><p> In my work, I first investigated the requirements for the cortical recruitment of NuMA and dynein, which had never been thoroughly addressed. I revealed that NuMA is required to recruit the dynein/dynactin complex to the cell cortex of cultured epidermal cells. In addition, I found that interaction with LGN is necessary but not sufficient for cortical NuMA recruitment. This led me to examine the role of additional NuMA-interacting proteins in spindle orientation. Notably, I identified a role for the 4.1 protein family in stabilizing NuMA's association with the cell cortex using a FRAP (fluorescence recovery after photobleaching)-based approach. I also showed that NuMA's spindle orientation activity is perturbed in the absence of 4.1 interactions. This effect was demonstrated in culture using both a cortical NuMA/spindle alignment assay as well as a cell stretch assay. Interestingly, I also noted a significant increase in cortical NuMA localization as cells enter anaphase. I found that inhibition of Cdk1 or mutation of a single residue on NuMA mimics this effect. I also revealed that this anaphase localization is independent of LGN and 4.1 interactions, thus revealing two independent mechanisms responsible for NuMA cortical recruitment at different stages of mitosis. </p><p> After gaining a deeper understanding of how NuMA is recruited and stabilized at the cell cortex, I then sought to investigate how cortical NuMA functions during spindle orientation. NuMA contains binding domains in its N- and C-termini that facilitate its interactions with the molecular motor dynein and MTs, respectively. In addition to its known role in recruiting dynein, I was interested in determining whether NuMA's ability to interact directly with MTs was critical for its function in spindle orientation. Surprisingly, I revealed that direct interactions between NuMA and MTs are required for spindle orientation in cultured keratinocytes. I also discovered that NuMA can specifically interact with MT ends and remain attached to depolymerizing MTs. To test the role of NuMA/MT interactions in vivo, I generated mice with an epidermal-specific in-frame deletion of the NuMA MT-binding domain. I determined that this deletion causes randomization of spindle orientation in vivo, resulting in defective epidermal differentiation and barrier formation, as well as neonatal lethality. In addition, conditional deletion of the NuMA MT-binding domain in adult mice results in severe hair growth defects. I found that NuMA is required for proper spindle positioning in hair follicle matrix cells and that differentiation of matrix-derived progeny is disrupted when NuMA is mutated, thus revealing an essential role for spindle orientation in hair morphogenesis. Finally, I discovered hyperproliferative regions in the interfollicular epidermis of these adult mutant mice, which is consistent with a loss of ACDs and perturbed differentiation. Based on these data, I propose a novel mechanism for force generation during spindle positioning whereby cortically-tethered NuMA plays a critical dynein-independent role in coupling MT depolymerization energy with cortical tethering to promote robust spindle orientation accuracy. </p><p> Taken together, my work highlights the complexity of NuMA localization and demonstrates the importance of NuMA cortical stability for productive force generation during spindle orientation. In addition, my findings validate the direct role of NuMA in spindle positioning and reveal that spindle orientation is used reiteratively in multiple distinct cell populations during epidermal morphogenesis and homeostasis.</p> / Dissertation

The author raises the question of what black women do to resist acts taken by the government to control their bodies such as the welfare queen trope. Many authors demonstrate that the welfare queen is used to control black women as a labor force as well as their reproduction. An infrapolitical reading of black hair tutorials is done to analyze the ways that black hair care is a form of political resistance. Robin Kelley's use of infrapolitics to understand actions taken by working class black people is used as a model.