Caenorhabditis elegans optionally enter into a dauer diapause phase that results in a prolonged life in a semi-dormant state. Entry into and recovery from dauer diapause includes many physical changes in body structure, physiology, and gene expression. Entry into dauer diapause is regulated by several signaling pathways including transforming growth factor (TGF-β). Autophagy plays an important role in dauer formation and recover. During dauer transformation autophagy is up-regulated and may play a role in remodeling the molecular structure for long term survival during dauer diapause. This research helps determine the role of autophagy in dauer development and recovery mediated through the TGF-β signaling pathway. This research also determines in which tissue autophagy is necessary for dauer formation and recovery through TGF-β signaling. This research is shedding light on the function of autophagy in the TGF-β signaling pathway, both processes of which have been linked to tumorigenesis, heart disease and cancer. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

The inevitable aging process can be partially attributed to the accumulation of oxidative damage that results from the action of free radicals. Methionine sulfoxide reductases (Msr) are a class of enzymes that repair oxidized methionine residues. The two known forms of Msr are MsrA and MsrB which reduce the R- and S- enantiomers of methionine sulfoxide, respectively. Our lab has created the first genetic animal model that is fully deficient for any Msr activity. Previously our lab showed that these animals exhibit a 20 hour delay in development of the third instar larvae (unpublished data). My studies have further shown that the prolonged third-instar stage is due to a reduced growth rate associated with slower food intake and a markedly slower motility. These Msr-deficient animals also exhibit decreased egg-laying that can be attributed to a lack of female receptivity to mating. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2016. / FAU Electronic Theses and Dissertations Collection

Decline in cardiac pump function is a hallmark of aging where mitochondrial decay is an important underlying cause. Although certainly multifactorial in nature, both dysfunction of the machinery involved in the chemiosmotic process of energy transduction and lower capacity to maintain fatty acid-driven respiration are identified as intrinsic factors of mitochondrial decay in the aged myocardium. Age-associated destabilization of electron transport supercomplexes as a potential factor of mitochondrial decay in the rat heart. Defective operation of the electron transport chain (ETC) constitutes a key mechanism involved in the age-associated loss of mitochondrial energy metabolism. Nevertheless, the molecular events underlying inefficient electron flux that ultimately leads to higher superoxide appearance and impaired respiration are not fully known. As recent biophysical evidence shows that the ETC may form large macromolecular assemblies (i.e. supercomplexes) that disintegrate in certain pathologies (e.g. heart failure or Barth syndrome) reminiscent of aging, we investigated the hypothesis that alterations in supercomplexes are partly responsible for the age-related loss of cardiac ETC function. In this dissertation, age-associated changes in supercomplex organization and stability were investigated in subsarcolemmal (SSM) and interfibrillary (IFM) mitochondria isolated from cardiac tissue from young (3-5 months) and old (24-28 months) male Fischer 344 rats. Blue native-PAGE (BN-PAGE) analysis of digitonin-solubilized mitochondrial membranes coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to investigate supercomplex organization. Results show that both SSM and IFM display supercomplexes comprised of various stoichiometries of complexes I, III and IV (never complex II), which typically organize as high mass (1500-2300 kDa) assemblies containing up to four copies of complex IV (i.e. I���III���IV[subscript N]-type supercomplexes). Interestingly, analysis of IFM proteins showed that, in general, supercomplex levels declined by up to 15 % (p < 0.05) with age; however, different degrees of supercomplex deterioration were observed, depending on the particular supercomplex investigated. Supercomplexes of the highest molecular weights (i.e. 1900-2300 kDa), which were also composed of the most complex stoichiometries (i.e. I1III2IVN, N ��� 2), were primarily lost with age. In particular, I���III���IV���, I���III���IV��� and I���III���IV��� supercomplexes were found to decline by 13% (p < 0.05), 30% (p < 0.05) and 45% (p < 0.05), respectively, on an age basis. Therefore, the age-associated loss of supercomplexes in IFM stems from destabilization of the assemblies that comprise several copies of complex IV, which could partially limit proper electron transfer to O��� for its reduction, affecting mitochondrial respiratory capacity. In contrast to IFM, the aging defects of SSM supercomplexes appeared to be confined to the assembly comprised of only one copy of complex IV (I���III���IV���, 1700 kDa) (37% loss; p = 0.06), while the higher molecular weight supercomplex sub-types that were most affected in IFM (i.e. I���III���IV[subscript N], N ��� 2) were not significantly altered with age. Thus, the results from this dissertation indicate that mitochondria from different subcellular locations in the myocyte show different degrees of supercomplex destabilization in the aging rat heart. The more robust supercomplex deficits noted for IFM fit well with previous observations that electron transport characteristics of this subpopulation are more adversely affected with age than SSM. Although the underlying factor(s) of supercomplex deterioration are not fully known, the hypothesis that age-related alterations of certain constituents of the IMM (e.g. cardiolipin) may be important factors of supercomplex destabilization in cardiac mitochondria was investigated in this dissertation. To this end, LC-MS/MS characterization of supercomplex proteins and HPLC analysis of cardiolipin were used as approaches to elucidate potential factor(s) of supercomplex destabilization in the aging rat heart. Age-related alterations of cardiolipin levels and its acyl-chain content showed a strong parallel to the age-associated destabilization of supercomplexes. Specifically, cardiolipin levels declined by 10% (p < 0.05) in IFM, the mitochondrial subpopulation displaying the highest degree of supercomplex deterioration. In addition, the content of (18:2)���-cardiolipin, the predominant species in the heart, was found to decline by 50% (p < 0.05) on average in both populations of cardiac mitochondria. Therefore, the data presented in this dissertation indicate that changes in cardiolipin may be at least one of the factors involved in supercomplex destabilization in the aging heart. Age-related decline in carnitine palmitoyltransferase I (CPT1) activity as a mitochondrial lesion that limits fatty acid catabolism in the rat heart. Loss of fatty acid utilization, another intrinsic factor of mitochondrial decay in the aged myocardium, has been associated with age-related alterations in the activity of carnitine palmitoyltransferase 1 (CPT1), the rate-controlling enzyme for overall fatty acid ��-oxidation. Nevertheless, the exact molecular mechanism involved in the age-related loss of fatty acid-driven bioenergetics is not fully understood. In this dissertation, it was also investigated whether the aging lesion for fatty oxidation lies in a particular mitochondrial subpopulation or more generally results from cardiac decrements in L-carnitine levels. In order to clarify the role of each one of these factors, the effect of long-term dietary supplementation with the L-carnitine analogue, acetyl-L-carnitine (ALCAR), was also investigated. Results show that aging selectively decreases CPT1 activity in IFM by reducing enzyme catalytic efficiency for palmitoyl-CoA. IFM displayed a 28% (p < 0.05) loss of CPT1 activity, which correlated with a decline (41%, p < 0.05) in palmitoyl-CoA-driven state 3 respiration. Interestingly, SSM had preserved enzyme function and efficiently utilized palmitate. Analysis of IFM CPT1 kinetics showed both diminished V[subscript max] and K[subscript m] (60% and 49% respectively, p < 0.05) when palmitoyl-CoA was the substrate. However, no age-related changes in enzyme kinetics were evident with respect to L-carnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics. In conclusion, this dissertation presents a characterization of age-associated alterations in the macromolecular organization of the IMM components that could partly explain the loss of mitochondrial oxidative capacity that affects the aging heart. In addition, the characterization of an age-related lesion of the controlling enzyme for ��-oxidation is presented as another important factor that limits mitochondrial function and energy metabolism in cardiac mitochondria. / Graduation date: 2013

Orientadores: Lucia Helena Innocentini Mei, Joceli Maria Giacomini Angelini / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Quimica / Made available in DSpace on 2018-08-15T13:39:32Z (GMT). No. of bitstreams: 1 Noronha_Fabio_M.pdf: 6615415 bytes, checksum: f72688fb0000126501c64a7267950cb0 (MD5) Previous issue date: 2010 / Resumo: Atualmente, os materiais utilizados como isoladores elétricos vêm sendo substituídos por materiais poliméricos por apresentarem vantagens em relação aos isoladores cerâmicos. Dentre estas vantagens, podem-se citar maior desempenho, melhor resistência ao vandalismo e menor peso. O objetivo desta dissertação foi o estabelecimento de desenvolver requisitos de desempenho para os Isoladores Poliméricos (EPDM- Monômero Dieno/Etileno/Propileno e Silicone) usados na rede elétrica, através de resultados obtidos em ensaios de envelhecimento natural e artificial, tendo como enfoque as linhas de transmissão de 69 kV e 138 kV. Foi realizado um estudo do estado da arte em Isoladores Poliméricos e do estado atual de aplicação e desempenho dos mesmos em campo. Estudos experimentais foram desenvolvidos em produtos retirados de campo e produtos novos, envelhecidos artificialmente em laboratório, segundo metodologias aplicáveis a polímeros. Em paralelo foram estudadas mantas elastoméricas de Silicone e EPDM para elaboração de critérios comparativos. Através dos resultados obtidos, foram sugeridos alguns requisitos de desempenho que poderão ser utilizados em especificações dos mesmos. Nesta dissertação, são apresentados, principalmente, estes resultados obtidos por meio das técnicas de ensaio de Tensões Elétricas, Rugosidade, Densidade, Dureza, FTIR-Infravermelho com Transformada de Fourier, DSC-Calorimetria Exploratória, DMTA-Análise Térmica Dinâmico Mecânica e Resistência à Tração. Os resultados obtidos mostraram a importância de controle da rugosidade bem como da necessidade de aditivação do polímero com sistema de termo e foto estabilização / Abstract: Currently, the materials used as electrical insulators are being replaced by polymeric materials have advantages as compared to ceramic insulators. Among these advantages, we can cite higher performance, better resistance to vandalism and lower weight. The objective of this thesis was the establishment of developing performance requirements for Polymeric Insulators (EPDM monomer diene / ethylene / propylene and Silicone) used in power systems, through results from trials of natural and artificial aging, focusing on the lines transmission of 69 kV and 138 kV. We conducted a study of the state of the art in Polymeric Insulators and current state of implementation and performance of the same field. Experimental studies have been developed into products removed from the field and new, artificially aged in the laboratory, according to the methods applied to polymers. Were studied in parallel webs of silicone elastomer and EPDM for developing benchmarks. Through the results, suggested some performance requirements that could be used in the same specifications. In this thesis, are presented, mainly, these results obtained by the techniques of test voltages, roughness, density, hardness, FTIR-Fourier Transform Infrared, Scanning Calorimetry-DSC, DMTA Dynamic-Mechanical Thermal Analysis and Tensile Strength . The results showed the importance of controlling the roughness and the need for additives with the polymer system and picture stabilization term / Mestrado / Ciencia e Tecnologia de Materiais / Mestre em Engenharia Química