Made available in DSpace on 2014-10-09T12:26:12Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:09:47Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

Made available in DSpace on 2014-10-09T12:26:12Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:09:47Z (GMT). No. of bitstreams: 0 / Os estudos sobre as análises de cabelos humanos têm sido assunto de contínuo interesse por se tratar de uma importante ferramenta para a avaliação de níveis de elementos traço no corpo humano. O interesse por este tecido é para o uso na monitoração de exposição ambiental ou ocupacional, para identificação da intoxicação e/ou envenenamento por metais tóxicos, na avaliação do estado nutricional, na diagnose e prevenção de doenças e nas ciências forenses. Há inúmeras vantagens na análise de cabelos quando comparados com as de outros tecidos ou fluidos biológicos, tais como sangue, urina, saliva e órgãos. Entretanto há controvérsias sobre o uso das análises de cabelos em razão da dificuldade em estabelecer os valores confiáveis de referência para as suas concentrações de elementos traço. O objetivo deste estudo foi avaliar os fatores que afetam nas concentrações de elementos em cabelos humanos e determinar os elementos em cabelos de uma população de indivíduos considerados saudáveis e residentes na área metropolitana de São Paulo, utilizando o método de análise por ativação com nêutrons (NAA). As amostras de cabelo coletadas da região occipital da cabeça foram cortadas em pequenos fragmentos, lavadas e secas para análise. As alíquotas de amostras de cabelo, juntamente com padrões sintéticos de elementos foram irradiados por 16 h sob fluxo de nêutrons térmicos de cerca de 5 x 1012 n cm-2 s-1 do reator nuclear IEA-R1 para a determinação de As, Br, Ca, Co. Cr, Cs, Cu, Fe, K, La, Na, Sb, Sc, Se e Zn. As radiações gama das amostras e dos padrões irradiados foram medidas em um espectrômetro de raios gama acoplado a um detector de Ge hiperpuro. Para avaliar a qualidade dos resultados com relação à exatidão e precisão foram analisados os materiais de referência certificados IAEA- 85 Human Hair e INCT-TL-1 Tea Leaves cujos resultados obtidos apresentaram, para a maioria dos elementos, boa concordância com os valores dos certificados (porcentagens de erros relativos inferiores a 10%) e boa precisão (coeficientes de variação inferiores a 13,6% ). As análises de uma amostra de cabelo em réplicas indicaram uma boa reprodutibilidade dos resultados, indicando a homogeneidade da amostra preparada. Os resultados das análises de cabelo com e sem tintura indicaram que a tintura afeta nos teores de elementos no cabelo em virtude da adsorção ou dessorção do elemento. As análises de cabelos de diferentes regiões da cabeça indicaram diferenças significativas para os elementos Fe, Sc, Se e Cr. Análises de cabelos de indivíduos residentes na área metropolitana de São Paulo indicaram que as concentrações de elementos nos cabelos dependem da idade, sexo e cor natural dos cabelos. Os resultados das análises de cabelos desta população mostraram que as médias das concentrações de elementos obtidas estão dentro da faixa de valores da literatura. / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP

The objective of this study was to evaluate the effect of pregnancy, breed, and hair coat on body temperature and sweating rate (SR) of hair sheep. St. Croix White (STX; = 9) and Dorper × STX (DRPX; = 9) ewes (3.6 yr of age) were evaluated over 4 d at 126 d of gestation (PREG) and over 4 d at 46 d postpartum (OPEN) in the shade and sun and in the morning (AM; 0900 to 1200 h) and afternoon (PM; 1300 to 1600 h) after a 20 min acclimation to each condition on each day. Data loggers recorded vaginal temperature (VT) at 10-min intervals for 96 h. Rectal temperature (RT) was measured using a digital veterinary thermometer, and respiration rate (RR) was measured as breaths per minute (bpm). Sweating rate was calculated from measured air properties passing over a shaved (300 cm) and unshaved area of the ewes' body using a portable calorimeter. Data were analyzed using GLM procedures of SAS (SAS Inst. Inc., Cary, NC) with breed, pregnancy status, sun exposure, and time of day as main effects. Mean temperature, relative humidity, temperature-humidity index, wind speed, and solar radiation on the days of data collection were 28.2°C, 82.8%, 80.3, 4.2 km/h, and 237.5 W/m, respectively. There was no difference ( > 0.10) in RT, RR, and SR between DRPX and STX ewes. The PREG ewes had lower RT ( < 0.007) and SR ( < 0.0001) and higher RR ( < 0.007) than OPEN ewes (38.5 ± 0.2 vs. 39.1 ± 0.2°C, 70.2 ± 3.1 vs. 88.3 ± 3.1 g⋅m⋅h, and 79.5 ± 2.2 vs. 72.1 ± 2.2 bpm, respectively). During the PM, RR, RT ( < 0.05), and SR ( < 0.006) were higher than in the AM. In the sun, RR ( < 0.001) and SR ( < 0.0001) were higher than in the shade, but there was no difference ( > 0.10) in RT. There was no difference in SR ( > 0.10) between the shaved and unshaved area of the ewe. The DRPX ewes had higher ( < 0.0001) VT than STX ewes. The PREG ewes had higher ( < 0.001) VT than OPEN ewes during the night time and lower VT than the OPEN ewes during the day time ( < 0.0001). The OPEN ewes had a greater ( < 0.009) daily range of VT than PREG ewes did (2.5 ± 0.4 vs. 1.1 ± 0.4°C, respectively), but there was no breed difference ( > 0.10). Hair coat did not have an influence on the SR of the ewes, and PREG ewes appeared to use increased respiration as opposed to sweating to help control RT. The narrower range of body temperature, measured as VT, of PREG compared to OPEN ewes may be a protective mechanism for the developing fetus.

C'est la pluralité des modèles d'études associés à l'utilisation de techniques variées qui permet aujourd'hui de mieux appréhender le caractère multifactoriel du vieillissement et d'en mieux caractériser les mécanismes-clés : dérégulation de la sensibilité aux nutriments, dysfonctionnement des mitochondries, instabilité génomique, raccourcissement des télomères, altérations épigénétiques, modifications post-traductionnelles non-enzymatiques des protéines, altération des cellules souches, sénescence cellulaire et altération de la communication intercellulaire. Dans un premier temps, nos travaux de recherche in vivo sur le vieillissement du cheveu, chez l'homme et chez la femme, ont permis de caractériser de nouveaux marqueurs cliniques précoces de l'alopécie androgénétique, tels que les signes péripilaires et la diversité des diamètres, et d'établir un lien avec des paramètres biologiques, infiltrats inflammatoires et miniaturisation des follicules pileux, respectivement. De plus, chez la femme non ménopausée, chez qui l'alopécie peut être difficile à diagnostiquer de par son caractère multifactoriel, nous avons pu établir un lien entre le statut en fer et la chute des cheveux. Dans un second temps, nos travaux in vivo sur le vieillissement de la peau chez la femme ménopausée ont permis d'attribuer une signature biologique aux effets cliniques de la DHEA (déhydroépiandrostérone) en application topique, aussi bien au niveau du derme que de l'épiderme. Nous avons aussi caractérisé l'effet d'un C-Xyloside, précurseur de glycosaminoglycane, sur les 3 compartiments de la peau. / Today, the numerous study models associated with the use of various techniques allow a better understanding of the multifactorial nature of aging and a better characterization of the key mechanisms, including deregulated nutrient sensitivity, mitochondrial dysfunction, genomic instability, telomere shortening, epigenetic alterations, non-enzymatic post translational modification of proteins, alterations of stem cells, cellular senescence and impaired intercellular communication. Initially, our in vivo research studies on the aging hair in man and women have revealed new early clinical markers of androgenic alopecia such as peripilar signs and hair diameter diversity, and established a link with biological parameters, as inflammatory infiltrates and miniaturization of hair follicles, respectively. Furthermore, in pre-menopausal women in whom alopecia can be difficult to diagnose due to its multifactorial nature, we could establish a link between iron status and hair loss. Second, our in vivo studies on the aging skin in menopausal woman in whom the effects of age are particularly accentuated allowed to assign a biological signature to the clinical response to topical application of DHEA (dehydroepiandrosterone), both at the dermal and epidermal level of the skin. We also characterized the effect of a glycosaminoglycan C-Xyloside precursor on the 3 compartments of the skin.

The skin of mammals contains sebaceous glands (SGs) which are attached to the hair follicle (HF), and their best known function is to release sebum onto the skin surface via the HF canal. It has long been known that these two entities of the pilosebaceous unit are interconnected, but the extent to which the two ‘control’ one another was less clear. The current project set out to investigate the impact of the HF cycle on the SG. It was found that in a depilation- induced HF cycle, SG morphology altered drastically, with an increase in SG area (P<0.001), number of sebocytes (P<0.001), and individual sebocyte area (P<0.001) occurring after HF depilation. In SGs attached to a spontaneously cycling HF, none of the above was observed, indicating that spontaneous HF cycling does not affect SG morphology, whereas anagen induction by depilation is associated with altered SG morphology, likely as a result of HF trauma. Diacylglycerol acyltransferase 1 (DGAT1) is an enzyme known for its role in the production of various lipids. It was previously shown that DGAT1 knockout in mice caused SG atrophy, which was thought to be caused by an increased level of retinoic acid within the skin, which in turn caused atrophy of the gland. The current project aimed to further investigate the role of the DGAT1 enzyme in murine skin. Based on the results of the previous experiments, HF and SG morphology of spontaneously-cycling DGAT1 knockout mice were assessed. It was found that DGAT1 knockout caused delayed HF morphogenesis, altered HF cycling, increased HF length (P<0.001), more acute HF growth angle (P<0.001), increased SG apoptosis(P<0.001), decreased SG lipid content (P<0.001) and dysfunctional lipid droplet formation. The impact of DGAT1 knockout on HF morphology and cycling suggests that DGAT1 knockout causes alterations in the WNT/ beta-catenin signalling pathway, as these processes are highly controlled by this signalling pathway. In order to investigate the role of the DGAT1 enzyme in human HFs, and to investigate the hypothesis that DGAT1 may directly interact with the WNT/ beta-catenin signalling pathway, HFs were organ-cultured in the presence of a pharmacological DGAT1 inhibitor (AZD7687). It was found, at the transcriptional level, that one of the major canonical pathways affected by DGAT1 inhibition in human HFs was the WNT/ beta-catenin signalling pathway. DGAT1 inhibition was found to cause suppression of the WNT/beta-catenin signalling pathway via a down-regulation of a number of WNT/beta-catenin related genes. Overall, these results show that SG morphology is largely dependent upon HF homeostasis, and suggest that the DGAT1 enzyme may possess a previously unknown role, directly impacting the WNT/ beta-catenin signalling pathway.

Hår är en av de första märkbara aspekterna av vårt utseende och förmedlar indirekt många första intryck. Att ta hand om, klippa och dekorera hår är något som har varit med människor sedan historia började dokumenteras. Det är ett unikt drag hos människan och kan symbolisera religion, yrke, social status, identitet eller till och med hälsotillstånd. Hårfärger är uppfattade med en viss personlighet och över hela världen finns det flera olika genetiska egenskaper för hårets egenskaper och struktur. När man arbetar med berättande är håret en väldigt viktig del av designen och om den är välgjord kan den få liv och en egen identitet. I datorgrafikens värld finns det många sätt för en konstnär att skapa de delar som behövs för ett realistiskt hår. Det som ser trovärdigt ut kan dock vara väldigt individuellt för betraktaren, varje attribut uppfattas lite annorlunda från person till person. I slutändan är det upp till konstnären att bemästra en egen metod för att skapa en frisyr som går ihop med den konstnärliga visionen. / Hair is one of the first noticeable aspects of our appearances and will convey many indirect first impressions. Grooming and decorating hair is something that have been with humans since documented history. It is a unique human trait that can symbolize religion, occupation, social status, identity or even health itself. Hair colors are conceived with a certain personality to them and throughout the world there exists several different genetic attributes to hairs structure and texture. When working with storytelling, the hair is thus a very important part of the design, and if done well can live beyond the character in the story. In the world of computer graphics there are many ways in which an artist can create the parts necessary for an approach to realistic looking hair. What looks realistic can be very individual to the viewer, each visual trait looking somewhat different to each pair of eyes, and each method will also probably produce a different result. In the end, it is up to the artist to learn how to control the methods available and to create a hairstyle in line with the artistic vision.

Over the past decade the concept that the hair follicle plays an important role in cutaneous wound repair has been established. Several elegant lineage tracing studies have demonstrated that hair follicle derived cells contribute to the long term maintenance of the epidermis following repair, while an absence of hair follicles is known to delay repair. The exact mechanisms surrounding hair follicle derived repair are unknown. Moreover, while multiple stem cell niches are present within the hair follicle, their relative importance during wound repair is still unclear. The hair follicle is also a regenerative mini-organ, undergoing regular cycles of growth and regression throughout life, yet surprisingly this has not been previously investigated with respect to wound repair. Data presented in this thesis reveals an unappreciated, yet fundamental link between the independent processes of hair cycle and wound repair, with a substantial acceleration in the rate of repair (~50%) observed in anagen phase. Importantly, the hair follicle appears to play a global role in repair, with differences in the contribution of multiple cell types to wound repair. In addition, this thesis addresses the early kinetics of hair follicle wound response for the first time. Anagen hair follicles are found predisposed to a more rapid and extensive response to injury, suggesting a higher overall percentage of repair derived from the hair follicle in anagen phase. Surprisingly, the bulge stem cell region, while critical for hair cycle appears to play little role in the events immediately following injury, and is not required for initiation of re-epithelialisation. Gene expression profiling reveals numerous genes associated with anagen accelerated repair, and identifies altered modulation of the immune system as a key mechanism. Further, anagen wounds are associated with an upregulation of developmental transcription factors, which may imply a more regenerative healing phenotype. These data reveal numerous targets with the potential to accelerate repair, which now require validation for their therapeutic potential. These targets could be of importance in promoting the repair of chronic wounds, an area of unmet clinical need. More generally, this thesis has established hair cycle as an important experimental variable, which must be controlled for in all future in vivo murine wounding studies.

Prenatal stress has been correlated with adverse developmental outcomes affecting infant cognition and behavior. Previous studies have shown that prenatal stress can lead to increased susceptibility to adult disease but few studies have looked at the physiological stress response system by measuring the activity of the hypothalamicpituitary-adrenal (HPA) axis. Cortisol, the output of the HPA axis can be secreted in many different matrices (saliva, blood, urine, feces and hair). Most studies that do, only look at one measure of hormone production instead of examining multiple matrices. Additionally these studies do not look at the relationship between matrices. Hair provides a long-term assessment of cortisol hormone production as related to infant behavior. Four measures of cortisol representative of prenatal and postpartum periods were collected in a sample population of rhesus macaques at the NIH facility. No stress was applied to these animals and cortisol concentrations were assessed in maternal hair, infant hair, amniotic fluid, and mothers’ milk. These cortisol measures were then analyzed first to determine vii the relationships between the four measures and second to relate these cortisol values to infant behavior in the primate neonatal neurobehavioral assessment. Subjects of this study were 30 mothers and infants from the 2015 and 2016 breeding cohort. 25 of which, were unique dyads. Using four statistical analyses and 3 groupings of behavior, we found that maternal hair cortisol concentrations were correlated with different temperaments of infants, while milk cortisol concentrations were correlated with infant’s visual exploration of the environment. Additionally, an inverse relationship was found between hair cortisol concentrations and both hair cortisol concentrations with amniotic fluid cortisol. Together, the four statistical analyses show that Maternal HPA axis activation during and after pregnancy affects infant behavioral development 1 month postpartum.

Anthology web series about a black hair salon.

<p>Obesity is a medical condition whose rates have seen a rise in both the United States and worldwide in recent decades. Numerous studies have been done to understand obesity, and through the use of GWAS researchers have been able to find multiple genetic factors that can contribute to obesity in mammals. One proposed cause of obesity are genetic impacts on cilia formation in the CNS, which causes downstream effects on food intake and energy expenditure, causing obesity via overeating and decreased activity.</p> <p>In the first half of this thesis, I describe a study, in collaboration with the Berbari Lab at IUPUI, that explored the human chromosome 16:53801550-53808600 (GRCh37/hg19), an intron of the FTO alpha-ketoglutarate Dependent Dioxygenase (<i>FTO</i>) gene for transcriptional regulators that impact BMI and obesity. First, using control DNA, PCR, and gel-electrophoresis, we created an assay for 44 primer sets (forward and reverse) covering the genomic region. After optimizing the assay, we then selected 111 human DNA samples across three weight groups (underweight, normal weight, and obese) to sequence using the assay. The samples were selected from subjects enrolled in the Walsh Lab FDP study. Sequencing was completed using the Illumina MiSeq System, and sequenced results were viewed using the Integrative Genomics Viewer (IGV) program. Variants that showed in the results were analyzed across and within the weight groups, and their locations were researched for previously known BMI or enhancer activity using online genome browsers Ensembl and UCSC Genome Browser.</p> <p>The results of this study revealed two SNPs, rs8055197 and rs11642015, that provided the best correlation with the weight categories among the samples. These results were consistent with literature that previously linked these single-nucleotide polymorphisms (SNPs) to obesity, particularly in relation to genes that are regulated by <i>FTO</i> (<i>CUX1</i>, <i>POMC</i>, and <i>IRX3/5</i>). Both SNPs lie within areas that show high enhancer activity in neural crest cells, important cells for cilia formation. Although there were SNPs in high LD within both regions, these two SNPs were chosen due to their homologous variant locations within the mouse genome (rs8055197 - GRCm38/mm10 8:91376305; rs11642015 - GRCm38/mm10 8:91375651), which provides a means of testing this obesity correlation, with a proposed enhancer relationship through <i>FTO</i>, in mouse models. </p> <p>In the second half of this thesis, I explored new methods for quantitatively defining natural hair color categories, and attempted to find novel SNPs impacting hair color in a GWAS using the quantitative values as phenotypes. In previous publications, the development and validation of the HIrisPlex-S Prediction Tool for hair prediction was made using categorical hair colors, which were defined and classified by individual researchers or lab personnel. Using spectrophotometer measurements and HSV color values, we used a machine-learning tool to objectively classify sample hair photos into natural hair color classes. We then used this quantitative data as the input phenotype for a GWAS, using both linear regression and linear mixed model regression, to search for new genetic associations with these objectively defined hair color classes. Lastly, we also measured correlations between these hair color phenotypes and a SNP array consisting of all currently known pigment SNPs cited in recent literature.</p> <p>The results of this study showed that quantitative values can be used as a means of classifying human hair colors. Both models used in the GWAS highlighted previously known SNPs that contributed to quantitative hair color. By utilizing the linear mixed model approach which has the ability to generate more power due to the normalization of hidden population structure, there was one near genome-wide significant SNP found that is currently not linked with hair color, rs2037697 (<i>IQUB</i>), which showed strong associations with light brown hair (p-value = 1.83192E-07), however this would need to be confirmed with increased numbers to validate its association. </p> <p>The results of the correlation analysis showed that SNPs cited as having impacts on pigmentation (eye, skin, and hair) also show strong associations with these objectively defined quantitative hair color classes and these rankings may prove very useful as the field moves towards quantitative hair color prediction.</p>