Segundo dados da Organização Mundial de Saúde, até o ano de 2030 a diabetes será a sétima enfermidade causadora de morte no mundo. A diabetes se caracteriza pela variação do nível de glicose no sangue dada ingestão de alimentos ou realização de certas tarefas. Além disso, já é sabido pela comunidade científica atual que células cancerígenas possuem metabolismo diferente quando comparadas a células normais, consumindo uma maior quantidade de açúcar devido a essa anormalidade. No presente trabalho serão apresentados, basicamente, dois tipos de biossensores que possuem grande potencial para tornarem-se monitores contínuos de glicose. Ambos os biossensores utilizam a enzima glicose oxidase como catalisador específico da reação de oxidação do carboidrato. O primeiro apresenta estrutura em escala micrométrica, tem por objetivo a quantificação de glicose em solução em ambiente extracelular e se baseia no sistema EGFET (Extended Gate Field Effect Transistor) com substrato de Fluorine Tin Oxide (FTO). Além do mais, foram utilizados dois protocolos de imobilização da glicose oxidase: quitosana (com uma janela de detecção de 1 a 5mM de glicose) e glutaraldeído (com janela de detecção de 0 a 15 mM de glicose). O segundo apresenta estrutura em escala nanométrica, tem por objetivo a quantificação de glicose em ambiente intracelular e baseia-se no sistema de nanopipetas de quartzo. Com esse dispositivo foi possível estipular a concentração de glicose livre dentro de três linhas de células distintas: Fibroblastos humanos entre 0 e 2.8mM; MCF-7 maior que 4.7 mM; MDA-MB-231entre 3.6 e 4.5 mM. / According to the World Health Organization, until 2030 diabetes will be the 7th cause of death worldwide. This disease is characterized by variation on blood glucose levels due to ingestion of specific food and tasks performing. Moreover, it is already known that cancer cells have a different metabolism when compared to normal cells and these abnormal cells have a higher sugar intake due to this abnormality. This work will present, basically, two types of biosensors with great potential to become continuous glucose monitors. Both biosensors use the enzyme glucose oxidase as carbohydrate oxidation catalyzer. The first one presents a micro-metric structure and its goal is to quantify glucose concentration in an extracellular solution. This device is based in EGFET (Extended Gate Field Effect Transistor) system and uses FTO as substrate. Furthermore, two immobilization protocols were used to fix the enzyme to the FTO: chitosan (with final range of 1~5mM of glucose) and glutaraldehyde (with final range of 0~15mM of glucose). The second is a nano-structured biosensor based on nanopipette system and its goal is to quantify intracellular glucose concentration. With this device was possible to stipulate free glucose molecules inside different cell lines: between 0 and 2.8mM for human Fibroblasts; greater than 4.7 mM for MCF-7; and between 3.6 and 4.5 mM for MDA-MB-231.

Ao longo dos anos a medicina vem se desenvolvendo rapidamente e junto com ela desenvolvem-se os métodos e processos de diagnósticos. Estes métodos ficam mais rápidos, precisos e cada vez menos invasivos graças ao desenvolvimento de dispositivos diagnósticos a cada dia menores e que produzam respostas confiáveis. Os biossensores são, sem dúvida, os grandes responsáveis pela miniaturização, barateamento e rapidez de diversos métodos diagnósticos e procedimentos clínicos utilizados diariamente. Dentre os diferentes tipos de biossensores existentes, destacamos os biossensores embasados em transistores de efeito de campo (FETs), mais precisamente os biossensores a base de transistor de efeito de campo de porta estendida (EGFET). Analisamos nesse trabalho os procedimentos de medida utilizando filmes finos de óxido de estanho dopados com flúor (FTO) como membrana sensível a íons H+ acoplados à porta de um EGFET, que podem servir de base para a construção de um biossensor no futuro. Já existem artigos na literatura atual que fazem uso de FTO como membrana sensível a íons H+ e OH-. Entretanto, nenhum dos artigos disponíveis faz um bom controle de alguns parâmetros, em alguns casos relativamente simples, ou se fazem não deixam claro de que maneira estão controlando esses parâmetros. Tais parâmetros são de fundamental importância na resposta final dos sensores uma vez que eles interferem significativamente no sinal dos mesmos. Mostramos no presente trabalho que parâmetros como a luz, a sequência em que os pHs são medidos pela amostra, o procedimento de limpeza das amostras e até as características morfológicas das amostras são importantes no processo de adsorção e retirada de íons da superfície da membrana. Mostramos também que cada amostra necessita uma rotina diferente quanto à sequência de medidas e até mesmo procedimentos de limpeza para que seu rendimento seja máximo, e como diferentes amostras evoluem ao longo do tempo. Como solução aos problemas citados, descrevemos o uso correto de duas amostras que apresentaram reprodutibilidade em seus dados e invariância entre os resultados coletados por diferentes sequências de medidas. Por fim, deixamos uma proposta sobre a dinâmica que ocorre durante os processos de adsorção e retirada de íons H+ e OH- na superfície dos filmes. Com base em nossa proposta fizemos cálculos teóricos estimados da quantidade de cargas que são adsorvidas na superfície do filme para as diferentes situações encontradas durante os experimentos. / Over the years the medicine has been developing rapidly and along with it develop methods and diagnostic procedures. These methods become faster, more accurate and less invasive thanks to the development of diagnostic devices each day minors and producing reliable answers. The biosensors are undoubtedly the major responsible for miniaturization, cheaper and rapidity of various diagnostic methods and clinical procedures used every day. Among the different types of existing biosensors, we highlight the biosensors grounded in field effect transistors (FETs), more precisely the biosensor based in extended gate field effect transistor (EGFET). We analyzed on this work measurement procedures using tin oxide thin films doped with fluorine (or fluorine tin oxide FTO) as sensitive the membrane to H+ ions bounded to the gate of an EGFET, which can serve as a basis for building a biosensor in the future. Articles has already been written reporting the use of the FTO as sensitive membrane to ion H+ and OH-. However, none article available makes a good control of some parameters, in some cases relatively simple, or if they do not make it clear the way they are controlling these parameters. These parameters are of crucial importance in the final response of the sensors since they interfere significantly in signal of the sensors. So, we shown in this work, which parameters as light, the sequence in which the pHs are measured by the sample, the cleaning procedure of samples and even the morphological characteristics of the samples are important in the process of adsorption and ion withdrawal of membrane surface. We shown also that each sample requires a different routine on the following measures and even cleaning procedures for your maximum income is, and how different samples evolve over time. As a solution to the problems cited, we describe the correct use of two samples that showed reproducibility in your data and invariance between the results collected by different sequences of measures. Finally, we leave a proposal on the dynamics that occurs during adsorption processes and withdrawal ion H+ and OH- on the surface of the films. Based on our proposal did theoretical calculations estimated quantity of loads that are adsorb on the surface of the film for the different situations encountered during experiments.

Sensores são dispositivos capazes de captar um determinado sinal físico -químico do meio e converte-lo num sinal elétrico mensurável por meio de um transdutor. Biossensor é um sensor que tem como parte funcional um receptor biológico específico a determinado analito alvo. Os sinais físico-químicos experimentados por estes dispositivos são convertidos em sinais elétricos de magnitude proporcional à concentração de um ou mais compostos químicos. Neste trabalho, foi construído um sensor de pH utilizando filmes finos comerciais de óxido de estanho dopado com flúor (FTO) como receptor a íons. O sensor foi feito ligando-se amostras de FTO ao terminal de porta de um transistor de efeito de campo do tipo MOS (Metal Oxide Semiconductor). Quando colocado em solução, os íons presentes interagem com a amostra sendo adsorvidos na superfície do filme de FTO. O potencial gerado pelos íons adsorvidos modulam a tensão na porta do transistor e, desta maneira, pode -se determinar a concentração dos íons presentes na solução de acordo com a magnitude da resposta do transistor. A este tipo de dispositivo dá -se o nome de EGFET (Extended Gate Field Effect Transistor). O EGFET construído apresentou responsividade de 55 mV/pH e resposta linear em soluções de pH 2 ao 12. Através de técnicas de imobilização enzimática foi possível ligar covalentemente proteínas urease sobre a superfície dos filmes de FTO, convertendo o sensor de pH em biossensor de ureia. Soluções tampão com diferentes pHs e concentrações foram testadas e determinou -se que as condições ideais para o uso deste biossensor de ureia são soluções tampão com pH = 6 e concentração de 10mM. Nessas condições, o biossensor apresentou uma responsividade de 114,5 mV/p(ureia) e linearidade no intervalo de concentrações de ureia entre 3,2.10 -4 e 3,2.10 -2 mol/L. / Sensors are devices capable of capturing a certain physical-chemical signal from environment and convert it into a measurable electrical signal by a transducer. Biosensor is a sensor which has a biological sensing element as receptor specific to a particular target analyte. The physical-chemical signals experienced by these devices are converted into electrical signals with magnitude proportional to the concentration of one or more chemical compounds. In this work, we built a pH-sensor using commercial thin films of tin oxide doped with fluorine (FTO) as ions receptor. The sensor was made by linking FTO samples to the gate of a field effect transistor MOS type. In solution, the ions interact with the sample being adsorbed on the surface of FTO film. The potential generated by the ions adsorbed on film\'s surface modulate the gate voltage of the transistor and, in this way, we can determine the concentration of ions present in solution correlated with the magnitude of the transistor response. This kind of device is given the name of EGFET (Extended Gate Field Effect Transistor). The EGFET built exhibits sensitivity of 55 mV/pH and linear response in the range of pH 2 to 12. Through enzyme immobilization techniques we could covalently bind urease proteins on the surface of FTO film, changing the pH-sensor in urea biosensor. Buffer solutions with differents pHs and concentrations were tested and was determined that optimal environment conditions for this urea biosensor is buffer solutions with pH = 6 and 10mM of concentration. Under these conditions, the biosensor showed sensitivity of 114.5 mV/p(urea) and linear response in the range of 3,2.10 -4 to 3,2.10 -2 mol/L

While obesity is a world leading health problem, the most efficient treatment option for severely obese patients is Roux-Y gastric bypass (RYGB) surgery. However, there are large inter-individual differences in weight loss after RYGB surgery. The reasons for this are not yet elucidated and the role of genetics in weight loss-regulation is still not fully understood. The main aim for this thesis was to investigate the effects of common obesity-associated genetic variants and their effect on weight loss and food intake. We examined if the weight loss two years following RYGB surgery depends on the  FTO genotype, as well as pre-surgery vitamin D status. For FTO AA-carriers, the surgery resulted in a 3% per-allele increased excess BMI loss (EBMIL; P=0.02). When split by vitamin D baseline status, the EBMIL of vitamin D deficient patients carrying AA exceeded that of vitamin D deficient patients carrying TT by 14% (P=0.03). No such genotypic differences were found in patients without pre-surgery vitamin D deficiency. As the influence of individual single nucleotide polymorphisms may be small, we identified a novel method to combine SNPs into a genetic risk score (GRS). Using the random forest model, SNPs with high impact on weight loss after RYGB surgery were filtered out. An up to 11% lower EBMIL with higher risk score was estimated for the GRS model (p=0.026) composed of seven BMI-associated SNPs (closest genes: MC4R, TMEM160, PTBP2, NUDT3, TFAP2B, ZNF608 and MAP2K5). Pre-surgical hunger feelings were found to be associated with EBMIL and the SNP rs4846567. Before surgery, patients filled out the Three Factor Eating Questionnaire and were genotyped for known BMI and waist-hip ratio (WHR) associated SNPs. Patients with the lowest hunger scores had up to 32% greater EBMIL compared to the highest scoring patients (P=0.002). TT-allele carriers of rs4846567 showed a 58% lower hunger feelings. TT- carriers also showed a 51% decrease in disinhibition, but no significant impact on cognitive restraint was observed. Due to the association of eating behaviour and weight loss, acute effects on DNA methylation in response to a food intake intervention of a standardized meal were also investigated. After food intake, 1832 CpG sites were differentially methylated compared to the baseline after multiple testing correction. When adjusted for white blood cell fractions, 541 CpG sites remained. This may be interpreted as that the immune system is playing an active role in the response to food intake and highlights the dynamic nature of DNA-methylation. These findings will contribute to a better care for morbidly obese patients. Post-surgical treatment may be optimized so that patients with a less favourable genetic profile may receive additional support for weight loss and weight management. This may be considered as a step in the transition towards personalized medicine.

Reversible adenosine methylation (N6-methylation; m6A) at the RNA level was described in connection to the regulation of RNA fate. The N6-methyladenosine pathway is important for cognitive function and mechanisms related to memory, including the regulation of adult neurogenesis and synaptic plasticity. The objective of this study was to test the hypothesis that a decreased activity of the RNA-demethylase FTO is associated with improved cognitive function in rats. The RNA-demethylase FTO is a key regulator of the m6A pathway. In this study, we administered MO-I-500, a pharmacological inhibitor of FTO in TgF344-AD transgenic rats, which resulted in an improvement of spatial cognition. We further investigated the cognitive enhancement induced by a caloric restriction as a possible compensatory mechanism of cognitive disorders and its effect on the proteins regulating the N6-methyladenosine pathway. Long-term caloric restriction ameliorated cognitive functions and led to changes in the expression of the major proteins controlling the m6A pathway (FTO, METTL3) which are consistent with the aforementioned hypothesis. Although we do not know the exact mechanism of action, these findings support the hypothesis that m6A pathway regulators, such as the FTO demethylase, may be a promising molecular target for...

Obesity is a complex and a highly individualized disease and the molecular mechanisms behind this disorder need to be better elucidated. Identification of genes and genetic variants that are involved provide opportunities to establish a genetic understanding of the disease. These findings may also provide more rational approaches to therapy, either by identifying underlying causes or point out the need for different treatments. In addition, the timing and severity of obesity may provide insights into the aetiology of obesity and also identify age-specific determinants of weight gain. Recently, genome-wide association studies have led to a rapid progress in our understanding of the genetic basis of various diseases and candidate genes for obesity have been identified. The overall aim of this thesis was to investigate the genetic impact on severity of childhood obesity and the associations between obesity and genetic variants in the fat mass and obesity associated gene, FTO, and MGAT1, the gene encoding mannosyl (α-1,3-)-glycoprotein β-1,2-N-acetyl-glucosaminyltransferase. We show that the impact of parental body mass index (BMI) on the severity of obesity in children is strengthened as the child grows older, whereas the age at obesity onset is of limited importance. By association studies, we show that single nucleotide polymorphisms downstream MGAT1 influence susceptibility to obesity. Moreover, these variants affect the levels of unsaturated fatty acids and desaturase indices, variables previously shown to correlate with obesity. Furthermore, one variant in the first intronic region of FTO is associated with obesity among children but not with BMI or other measures of adiposity at older ages. However, this variant shows a weight-dependent association with cognitive function among elderly men. By direct sequencing, we identified novel variants in FTO, affecting glucose homeostasis in a BMI-independent manner. Furthermore, we found gender specific effects for FTO, both regarding obesity susceptibility and related phenotypes.

Studies indicate that overweight and obesity protect against HIV-disease progression in antiretroviral therapy (ART)-naïve patients. We examined retrospectively the relationship of overweight/obesity with HIV-disease progression in ART-naïve HIV+ adults in Botswana in a case-control study with 18-month follow-up, which included 217 participants, 139 with BMI 18.0-24.9 kg/m2 and 78 with BMI ≥25 kg/m2. Archived plasma samples were used to determine inflammatory markers: leptin and bacterial endotoxin lipopolysaccharide (LPS), and genotype single nucleotide polymorphisms (SNPs) of the Fat Mass and Obesity Associated Gene (FTO). At baseline, BMI was inversely associated with risk for AIDS-defining conditions (HR=0.218; 95%CI=0.068, 0.701, P=0.011), and higher fat mass was associated with reduced risk of the combined outcome of CD4+cell count ≤250/µL and AIDS-defining conditions, whichever occurred earlier (HR=0.918; 95%CI=0.847, 0.994, P=0.036) over 18 months, adjusting for age, gender, marriage, children, and baseline CD4+cell count and HIV-viral load. FTO-SNP rs17817449 was associated with BMI (OR=1.082; 95%CI=1.001, 1.169; P=0.047). Fat mass was associated with the risk alleles of rs1121980 (OR=1.065; 95%CI=1.009, 1.125, P=0.021), rs8050136 (OR=1.078; 95%CI=1.021, 1.140; P=0.007), and rs17817449 (OR=1.086; 95%CI=1.031, 1.145; P=0.002), controlling for age, gender, tribe, total energy intake, and activity. There were no associations of SNPs with markers of disease progression. Leptin levels were positively associated with BMI (β=1.764; 95%CI=0.788, 2.739; P=0.022) and fat mass (β=0.112; 95%CI=0.090, 0.135; P<0.001), but inversely with viral load (β=-0.305; 95%CI=-0.579, -.031; P=0.030). LPS levels were inversely associated with BMI (OR=0.790, 95%CI=0.630, 0.990; P=0.041), and fat mass (OR=0.852, 95%CI=0.757, 0.958; P=0.007) and directly with viral load (OR=2.608, 95%CI=1.111, 6.124; P=0.028), adjusting for age, gender, smoking and %fat mass. In this cohort, overweight/obesity predicted slower HIV-disease progression. Obesity may confer an advantage in maintaining fat stores to support the overactive immune system. FTO-SNPs may contribute to the variation in fat mass; however, they were not associated with HIV-disease progression. Our findings suggest that the obesity paradox may be explained by the association of increased LPS with lower BMI and higher viral load; while viral load decreased with increasing leptin levels. Studies in African populations are needed to clarify whether genetic variation and inflammation mediate the obesity paradox in HIV-disease progression.

<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>

Submitted by Maria Medeiros (maria.dilva1@ufcg.edu.br) on 2018-10-19T13:45:26Z No. of bitstreams: 1 JACYELLI CARDOSO MARINHO DOS SANTOS - DISSERTAÇÃO (PPGEQ) 2017.pdf: 1181213 bytes, checksum: 831251b803f8b040ed40be41dac19267 (MD5) / Made available in DSpace on 2018-10-19T13:45:26Z (GMT). No. of bitstreams: 1 JACYELLI CARDOSO MARINHO DOS SANTOS - DISSERTAÇÃO (PPGEQ) 2017.pdf: 1181213 bytes, checksum: 831251b803f8b040ed40be41dac19267 (MD5) Previous issue date: 2017-03-17 / Atualmente existem três gerações de células solares, sendo a mais recente a Dye-Sensitized Solar Cells-DSSC, também denominadas como células de Grätzel. Uma das partes essenciais desse tipo de célula solar são os eletrodos transparentes formados a partir de óxido metálicos, sendo o mais comum o de estanho (SnO2). Esse óxido vem sendo largamente utilizado como película condutora em vidro, uma vez que combina características como condutividade elétrica com transparência na região do visível do espectro eletromagnético, podendo assim ser aplicado a- uma grande quantidade de dispositivos eletrônicos. Porém, devido o dióxido de estanho se tratar de um material de alto valor agregado, alternativas para sua obtenção estão sendo estudadas, um desses estudos é a utilização de cloreto de estanho para formação do filme condutor em vidro. Dessa forma, esse trabalho tem como objetivo obtenção de uma solução promotor de estanho a partir de liga de solda comercial. Duas técnicas foram avaliadas, o tratamento ácido e o hidrometalúrgico. Amostras de liga de solda (Sn/Pb) foram submetidas a um tratamento ácido e térmico, com a realização da separação chumbo do estanho e formação da solução de cloreto de estanho. Foram realizados ensaios de dopagem com a utilização da solução de cloreto de estanho juntamente com fluoreto de amônia, utilizadas na formação dos filmes em superfícies de placas de vidro. O parâmetro de verificação da formação do filme condutor foi a resistência elétrica, obtida a partir da condutividade elétrica. A solução de cloreto de estanho gerada pelo processo hidrometalúrgico da liga de solda possibilitou a deposição de uma camada condutora em vidro, sendo resistência obtida com filme condutor com essa metodologia foi de 0,4 a 3 KΩ.Apesar da resistência estar acima da dos valores comerciais, a obtenção da solução de cloreto de estanho da partir da solda comercial, ou de lixo eletrônico, minimiza significativamente o custo de produção dos filmes finos condutores, tornando ainda o processo reciclável, se aproveitada a liga de solda de lixos eletrônicos. / There are currently three generations of solar cells, the most recent being the Dye-Sensitized Solar Cells-DSSC, also referred to as Grätzel cells. One of the essential parts of this type of solar cell is transparent electrodes formed from metal oxide, the most common being tin(SnO2). T-his oxide has been widely used as a conductive glass film, since it combines characteristics such as electrical conductivity with transparency in the visible region of the electromagnetic spectrum, and can be applied to a large number of electronic devices. However, because tin dioxide is a high value-added material, alternatives for its production are being studied, one of these studies is the use of tin chloride to form the conductive glass film. Thus, this work has as objective to obtain a solution promoter of tin from commercial welding alloy. Two techniques were evaluated: acid and hydrometallurgical treatment. Samples of solder alloy (Sn/Pb) were subjected to an acid and thermal treatment, with the lead separation of the tin and formation of the tin chloride solution. Doping tests were carried out using the tin chloride solution together with ammonium fluoride used in the formation of films on glass plate surfaces. The verification parameter of the conductive film formation was the electrical resistance, obtained from the electrical conductivity. The solution of tin chloride generated by the hydrometallurgical process of the weld alloy allowed the deposition of a conductive layer in glass, and resistance obtained with conductive film with this methodology was of 0.4 to 3 KΩ. Although the resistance is above commercial values, obtaining the tin chloride solution from the commercial solder or electronic waste minimizes significantly the cost of production of the conductive thin films, making the process even more recyclable, if the alloy is used Soldering of electronic waste.

Die hier vorliegende Arbeit zeigt die molekulare Evolution des Melatoninrezeptor 1 B-Gens (MTNR1B) und des Fat Mass and Obesity Associated-Gens (FTO). Für beide Gene wurden in genomweiten Assoziationsstudien (GWAS) Varianten entdeckt, welche zu der Entwicklung einer Adipositas bzw. deren Folgeerkrankungen beitragen können. So wurde für Einzelbasenaustausche (SNPs) im MTNR1B (rs10830963, rs4753426) eine Verschlechterung der Nüchternglukose sowie der Insulinausschüttung gezeigt. Zudem wurde für die Allelfrequenz des rs4753426 C-Allels ein Zusammenhang mit der täglichen Sonnenscheindauer beschrieben. Im FTO wurde eine (tagging) Variante im ersten Intron identifiziert (rs9939609), welche einen erhöhten Körpermasseindex (BMI) zu vermitteln scheint und robust repliziert werden konnte. Zusätzlich konnte in den Sorben, einer in der Lausitz ansässigen Volksgruppe, eine Variante im dritten Intron (rs17818902) beschrieben werden, die ein zusätzliches, stärkeres Assoziationssignal mit einem erhöhten BMI zeigte. Dies führte zu der Fragestellung, ob MTNR1B und FTO einer Konservierung unterlegen sind. Zudem interessierten populationsspezifische Unterschiede, um die Untersuchungen in den Kontext der Hypothese des sparsamen Genotyps stellen zu können. Demnach haben Individuen mit einer genetischen Veranlagung, die ihnen eine effizientere Energiespeicherung ermöglicht, zu Zeiten von Nahrungsmangel einen Fitness-Vorteil gegenüber Nicht-Trägern. Die Konservierung zwischen den Spezies wurde mit Phylogenetic Analysis by Maximum Likelihood (PAML) betrachtet, eine Analyse die auf dem Verhältnis von nichtsynonymen zu synonymen Basenaustauschen innerhalb einer kodierenden Sequenz beruht. Die Selektion innerhalb bzw. zwischen menschlichen Populationen wurde anhand verschiedener populationsgenetischer Variablen näher beleuchtet. Sowohl für MTNR1B als auch für FTO konnte gezeigt werden, dass sie über die betrachteten Spezies im Durchschnitt stark oder sehr stark konserviert sind, was die physiologische Relevanz dieser Gene untermauert. Für MTNR1B zeigte sich zudem, dass es auf dem Ast zum Menschen nicht konserviert, sondern positiv selektioniert ist. Dies kann als Anzeichen für durch die Umwelt bedingte Einflüsse gedeutet werden. Essentielle Residuen des Rezeptors sind jedoch auch hier hochgradig konserviert. Die populationsgenetischen Variablen implizieren bei beiden Genen eine nicht-neutrale Selektion. Während sich beim MTNR1B insbesondere populationsspezifische Unterschiede anhand des Fixierungsindex Fst zeigten, konnten für FTO marginal signifikante Korrelationen zwischen der Konservierung der Haplotypen und der Stärke der Assoziation mit BMI in den Sorben gezeigt werden. Für beide Gene kann die Hypothese des sparsamen Genotyps nicht prinzipiell ausgeschlossen werden, allerdings sind weitere Untersuchungen diesbezüglich von Nöten.