Rapid technological advances for the frequent monitoring of health parameters have raised the intriguing possibility that an individual's genotype could be predicted from phenotypic data alone. Here we used a machine learning approach to analyze the phenotypic effects of polymorphic mutations in a mouse model of Huntington's disease that determine disease presentation and age of onset. The resulting model correlated variation across 3,086 behavioral traits with seven different CAG-repeat lengths in the huntingtin gene (Htt). We selected behavioral signatures for age and CAG-repeat length that most robustly distinguished between mouse lines and validated the model by correctly predicting the repeat length of a blinded mouse line. Sufficient discriminatory power to accurately predict genotype required combined analysis of >200 phenotypic features. Our results suggest that autosomal dominant disease-causing mutations could be predicted through the use of subtle behavioral signatures that emerge in large-scale, combinatorial analyses. Our work provides an open data platform that we now share with the research community to aid efforts focused on understanding the pathways that link behavioral consequences to genetic variation in Huntington's disease.

The collection of samples of saliva is noninvasive and straightforward, which turns saliva into an ideal fluid for monitoring the adaptive response to training. Here, we investigated the response of the salivary proteins alpha-amylase (sAA), chromogranin A (sCgA), and the concentration of total protein (sTP) as well as salivary nitrite (sNO2) in relation to plasma catecholamines and plasma nitrite (pNO2), respectively. The variation in these markers was compared to the intensity and load of training during a 21-week training season in 12 elite swimmers. Overall, the salivary proteins tracked the concentration of plasma adrenaline and were inversely correlated with the training outcomes. No correlations were observed between sNO2 and pNO2. However, sNO2 correlated positively with the intensity and load of training. We argue that the decrease in sympathetic activity is responsible for the decrease in the concentration of proteins throughout the training season. Furthermore, the increase in nitrite is likely to reflect changes in hemodynamics and regulation of vascular tone. The association of the salivary markers with the training outcomes underlines their potential as noninvasive markers of training status in professional athletes.

Cultivated tomato, Solanum lycopersicum, is one of the most common fruits in the global food industry. Together with the wild tomato Solanum pennellii, it is widely used for developing better cultivars. MicroRNAs affect mRNA regulation, inhibiting its translation and/or promoting its degradation. Important proteins involved in these processes are ARGONAUTE and DICER. This study aimed to identify and characterize the genes involved in the miRNA processing pathway, miRNA molecules and target genes in both species. We validated the presence of pathway genes and miRNA in different NGS libraries and 6 miRNA families using quantitative RT-PCR. We identified 71 putative proteins in S. lycopersicum and 108 in S. pennellii likely involved in small RNAs processing. Of these, 29 and 32 participate in miRNA processing pathways, respectively. We identified 343 mature miRNAs, 226 pre-miRNAs in 87 families, including 192 miRNAs, which were not previously identified, belonging to 38 new families in S. lycopersicum. In S. pennellii, we found 388 mature miRNAs and 234 pre-miRNAs contained in 85 families. All miRNAs found in S. pennellii were unpublished, being identified for the first time in our study. Furthermore, we identified 2471 and 3462 different miRNA target in S. lycopersicum and S. pennellii, respectively.

Halophilic archaea thrive in hypersaline conditions associated with desiccation, ultraviolet (UV) irradiation and redox active compounds, and thus are naturally tolerant to a variety of stresses. Here, we identified mutations that promote enhanced tolerance of halophilic archaea to redox-active compounds using Haloferax volcanii as a model organism. The strains were isolated from a library of random transposon mutants for growth on high doses of sodium hypochlorite (NaOCl), an agent that forms hypochlorous acid (HOCl) and other redox acid compounds common to aqueous environments of high concentrations of chloride. The transposon insertion site in each of twenty isolated clones was mapped using the following: (i) inverse nested two-step PCR (INT-PCR) and (ii) semi-random two-step PCR (ST-PCR). Genes that were found to be disrupted in hypertolerant strains were associated with lysine deacetylation, proteasomes, transporters, polyamine biosynthesis, electron transfer, and other cellular processes. Further analysis revealed a ΔpsmA1 (α1) markerless deletion strain that produces only the α2 and β proteins of 20S proteasomes was hypertolerant to hypochlorite stress compared with wild type, which produces α1, α2, and β proteins. The results of this study provide new insights into archaeal tolerance of redox active compounds such as hypochlorite.

As sugestões da Comissão Examinadora e as Normas PGGB para o formato da Tese foram contempladas.