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MODULATION OF SIGNAL TRANSDUCTION ASSOCIATED WITH TYROSINE KINASE RECEPTORS BY THE FRAGMENT C-TERMINAL OF TETANUS TOXIN IN NERVOUS TISSUE.Summary: The neurotoxins clostridiales (CNTs) cause serious diseases such as tetanus and botulism. Both pathologies death comes at a high percentage and usually by suffocation and respiratory collapse. This ability to cause death in higher organisms is the responsibility of the activity metaloproteásica dependent zinc that have these toxins in the catalytic domain. However, in addition to the activity metaloproteásica have also discovered other pharmacological effects of the neurotoxins. The neurotoxins are complex protein structures that have acquired the ability to act in different systems across different mechanisms of action, such as blocking the uptake of certain neurotransmitters, or some of its precursors. Also, the tetanus toxin (TeTx) synthesized by Cl.tetani and producing a spastic paralysis, has other effects on various enzymes, not explainable by this action proteásica. In this thesis describes the activation of signaling pathways in the nervous tissue by tetanus toxin (TeTx) and its C-terminal domain of the 50 kDa heavy chain (Hc). These signaling pathways include the phosphorylation of the receptor TrkA and the phospholipase Cgamma-1 (PLCgamma-1), the translocation of classic and new isoforms of the protein kinase C (PKC) and the phosphorylation of cinasas regulated by extracellular signals (ERK -1 / 2) in sinaptosomas of rat brain (Work 1). Similar experiments in primary cultures of cortical neurons show the activation of Akt pathways and ERK1 / 2 (working 2). It also presents works that point to a neuroprotection exercised by the fragment NON TOXIC Hc front of the apoptotic death of granule neurons in the cerebellum (CGN) in low concentrations of potassium. Neuroprotection We believe that this may be due to the interaction with Hc portion of the receiver TrkB, growth factor receptor BDNF, leading to activation of at least three means of signaling: fostatidilinositol-3-quinasa (PI-3K) / protein kinase B , Ras / ERK and PLCgamma / PKC, as does the BDNF. He also characterized the action of blocking caspase-3 in the cellular mechanisms of protection (Work 3). Finally, in the same model above, CGN, also demonstrated the neuroprotective effect of fragment Hc-TeTX front of the apoptotic death induced by MPP +, decreasing cell death and chromatin condensation. In the process apoptótico induced by MPP + is the translocation of Bax from the cytosolic fraction to the mitochondrial fraction, the release of cytochrome c in the cytoplasm as well as the activation of the pro-caspasa-3. This process is inhibited by the apoptótico fragment Hc-TeTx (Work 4). Taken together, these works suggests that the fragment Hc-TeTx could be used as a neutrofina (NGB, BDNF, NT / 3, etc.) and produce actions anti-apoptóticas therapeutically targeted.
GENERACIÓ I ÚS OF MICROXIPS OF DNA PER AL'ESTUDI OF THE TRANSCRIPTIONAL RESPONSE TO PH ALCAÍ IN SARCCHAROMYCES CEREVISIAE.Author: VILADEVALL MASBERNAT LAIA. Year: 2004. University: AUTÓNOMA DE BARCELONA [ www.uab.es]. Place of defense: FACULTAD DE VETERINARIA. Place of preparation: ESCUELA DE POSTGRADO. CHARACTERISTICS OF ACTION OF GLP-1 ON LIPID METABOLISM IN THE ADIPOCYTE OF NORMAL AND DIABETIC RATS.Author: TRIGO GALVÁN M. VICTORIA. Year: 2004. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS. Place of preparation: FACULTAD C. BIOLOGICAS (UCM). Summary: The original contributions of the study can be summarized as follows: 1.Que in adipocyte of normal rats, the GLP-1, like insulin stimulates the activity of certain kinases, of which the MAPKS and any isoform of the PKC could be identified in its action lipolíticas and that unlike with insulin, an increase in the activation of PI3K, MAPKS but not p70s6k, would be essential in its effect lipogénico. 2. Peptides That counterparts LPG-1, E -4 and Ex9, both miméticos are the same in terms of their action lipogénica, which requires an increase in the activity not only of the same kinases, but also the p70s6k. And which of the two exendinas, only the former -4 is lipolítica, but unlike GLP-1, its action is not involved in the p70s6k. 3. Que in adipocyte of an experimental model of type 2 diabetes in rats, not just the basal activity of PI3K is higher than in the normal animal, but also the level incducido by GLP-1.Además, unlike with the rat normal, the GLP-1 stimulates the activity PKB, but not amending the p70s6k or, like insulin, the MAPKs. And that the effect lipolítico LPG-1 and the former -4 is maintained but , in contrast with insulin, the cells are insensitive to both regarding the lipogénesis STUDY OF THE MOLECULAR MECHANISMS THAT ALTER INSULIN RESPONSE IN RATS UNDERNOURISHED.Summary: Undernutrition maintains a high prevalence in the world. It is therefore a very significant health problem. Undernutrition established during stages of immaturity has a negative impact on many physiological and metabolic processes involving various body systems: inrnunitario, nervous, cardiovascular, etc.. As a result, undernourishment can encourage, or even cause directly, the development of a wide variety of diseases, such as diabetes type 2. In this paper, we have implemented a model of undernourishment which is of particular interest for the study of undernourishment to the currently undergoing millions of people in developed countries and not marginalized in many societies, as it is a model that fits most of the characteristics of these individuals: a complete restriction, ie protein, which starts at the most sensitive stage of development, pregnancy and extends along its entire life. The undernourished rats are normotolerantes to glucose, despite presenting hipoinsulinemia therefore, we find a table hypersensitivity to insulin. We conducted a study in cardiac and skeletal muscle of adult rats to discuss possible changes molecular explain this increase in its response to insulin and also we wanted to investigate whether the hypersensitivity presenting rats undernourished when they are adults, is now established during its infancy, specifically the 10 ddV, in the skeletal muscle and liver. Thus we find that: - The undernutrition increases the stimulation of insulin on the translocation of glucose transporters in the muscle of the adult rat: in skeletal muscle increases the translocation of GLUT-4, and this seems associated with an increase in its content and insulin receptors in the heart muscle, increasing the translocation of GLUT-I probably as a result of an increased activity of IP 3-kinasa and the Akt. - The rats that were undernourished infants from the last third of gestation are normotolerantes to glucose despite its poor response insulino-secretora. This is due, at least in part, to an increase in their responsiveness to insulin on the translocation of GLUT-4, which is linked to an increase in the number of receptors of the hormone as well as various stages of their way subsequent signal to the receiver. Undernutrition-established since the last third of pregnancy leads to increased GLUT-2 and GLUT-I in the liver of rats infant, as well as some signs of the way insulin. It is possible that this has resulted in a hypersensitivity tackle some of the hormonal responses liver.
CHLOROQUINE OF REGULATION BY TRANSCRIPTION OF GENES IN THE CASCADE ANTIOXIDANT IN FALCIPARUM MALARIASummary: Plasmadium falciparun is the causative agent of the most severe form of malaria in humanos.A spite of the amount of information that we move on and the vector of the parasite that causes this disease causes each year between 300 and 600 million new patients and between 1 and 3 million muertes.Por this reason are increasingly necessary studies led or understand the molecular bases that support the complex biology of the parasite. In this paper has developed a technique for real-time quantitative PCE implemented using probes tallo-bucle (molecular beacons) for the detection and quantification of the expression of mRNA in P.Falciporum.Por means of this methodology have been identified profiles transcription of genes in the cascade anti-oxidante the parasite to assess its role in the cycle intraeritrocítoc.Así it has studied the effect of the transcription of these genes in order to know the differences in the regulation of genica the cascade antioxidant between a lineage P. Falciporum resistant to the drug and a sensible.Los results indicate that the strains regulate their environment reducer differently, suggesting that the transcriptional control of the cascading antioxidant may explain the different susceptibilities of P.falciparum to chloroquine. CHARACTERIZATION OF THE ROLE OF GTPASAS RHO AND RAC IN THE ACTIVATION AND SIGNALING THE INTEGRINA LFA-1 IN LYMPHOCYTES TAuthor: SÁNCHEZ MARTÍN LORENA. Year: 2004. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS. Place of preparation: INSTITUTO DE FARMACOLOGÍA Y TOXICOLOGÍA. Summary: The integrina LFA-1 (alfaLbeta2, CD11a/CD18) is a key molecule in the lymphocyte migration and antigen presentation. These processes are associated with a further polarization of the morphology of lymphocyte-induced signals mediated LFA-1. In this context, the reorganization of the cellular cytoskeleton plays a role in regulating both the activity of LFA-1 in the morphological changes that average. Thus GTPasas Rho and Rac, because of the control exercised on the organization citoesquelética are good candidates regulators of the activity of LFA-1 and signals mediated by this integrina. The results presented in this thesis show that inhibition of GTPasa Rho, its effect ROCK or the GTPasa Rac induces despolimierización part of actin filaments, allowing the activation of LFA-1 aggregation induced in the membrane without increases his affinity for the ligand. Furthermore, the inhibition of Rho and ROCK induces an increase in the membership of ICAM-1 and changes in the morphology mediated LFA-1. The inhibition of Rho, Rac ROCK or induces activation of the tyrosine kinase PYK2 mediated by the interaction of LFA-1 active with his ICAM-1 and not in a direct way. These studies provide further information on the marking of LFA-1 to the cytoskeleton. So LFA-1 induces transient activation of the GTPasa Rac necessary for the induction of morphological changes. This signaling toward Rac, LFA-1 modulates the activity of Rac through two different pathways, one induces the activation of Rac through the phosphorylation and activation of GEF Vav, while the activation later shaft PI3K/Akt induced also by LFA-1, inactive Rac. ICLONACIÓN, EXPRESSION AND CHARACTERIZATION OF PENICILLIN ACILASAS OF STREPTOMYCES LAVENDULAE AND ACTINOPLANES UTAHENSISAuthor: TORRES BACETE JESÚS. Year: 2004. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS. Place of preparation: FACULTAD DE CIENCIAS BIOLÓGICAS - UCM. Summary: This research work describes the process of cloning and characterization of genes and pva aac encoding enzymes penicillin V acilasa of S.lavendulae (S / PVA) and aculeacina A acilasa of A.utahensis (AuAAC) respectively. Likewise, it describes the expression of both genes in Streptomyces lividans and functional characterization, as biocatalysts in the reactions of hydrolysis of natural penicillins, enzymes S / PVA and AuAAC. Finally proposes a method of purification for both enzymes and is a study of structural characterization of both the S / PVA recombinant as the AuAAC recombinant. REGULATION OF MITOCHONDRIAL BIOGENESIS IN NEONATAL RAT BRAIN BY THYROID HORMONEAuthor: MARTINEZ ALFARO BIENVENIDA. Year: 2004. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE FARMACIA. Place of preparation: FACULTAD DE MEDICINA.
Summary: Thyroid hormone plays a crucial role in brain development, however, the involvement of the mitochondria in the action of this hormone in the brain has been very controversial and has long been regarded it as negative. Our lab has previously shown that the brain of animals hiccups draft ideo s expression of the mitochondrial genome is diminished during development. Our goal in this work has been to conduct a detailed study of the effect of thyroid hormone on mitochondrial activity in different brain areas. Our results clearly show that the draft idea hormone regulates the activity of mitochondria free only in two areas of the brain: cerebral cortex and striped. So, we only observed in neonates hypothyroid a decrease in the ability of oxidative phosphorylation activity of the complex 1 and expression of the mitochondrial genome in these two areas, it has not observed any change in the hippocampus, cerebellum, thalamus, brain stem and mesencéfalo. In contrast to these results have not been observed in mitochondria synaptic changes of the cerebral cortex. The study of the incorporation of 13C from la- glucose various metabolites in the brain by nuclear magnetic resonance (NMR), suggest a lower oxygen consumption by the neuron s of the cerebral cortex. These results demonstrate a differential of T3 on mitochondria sinápticos terminals and the bodies of nerve. Finally all our results are consistent with the idea that T3 regulates mitochondrial activity, at least in part, through the regulation of the expression of the mitochondrial genome. REABSORCIÓ KIDNEY D'AMINOÀCIDS: ANÁLISI OF MUTACIONS OF SLC7A9, GENE CISTINÚRIA OF TIPUS B, I GENERACIÓ D'UN MODEL MURÍ KNOCKOUT OF SLC7A8Author: FONT LLITJÓN MARIONA. Year: 2004. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAT DE BIOLOGÍA. Place of preparation: CGMM-INSTITUT DE RECESCA ONCOLÓGICA. THE ANEXINASAuthor: GUZMÁN ARÁNGUEZ ANA. Year: 2004. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD CC. QUÍMICAS. Place of preparation: FAC. CC QUÍMICAS DPTO. BIOQUIMICA Y BIOLOGÍA MOLECULAR I. Summary: The anexinas are a famiba protein characterized by its ability to join biological membranes in the presence of calcium cored protein conserved N-terminal region and a highly variable in length and sequence. Although in vitro have been assigned a variety of functions, is still unknown what the physiological role of individual anexina. One of the most abundant members of this family is the anexina A5. In order to deepen the understanding of this protein has been carried out by the expression and characterization estructuralde the anexina A5 human, anexina A5 chicken, a mutant that it lacks 8 residues in the N-terminal region, as well as a chimerical protein consisting of the N-terminal end of the anexina A5 chicken and the core protein of the anexinaA5 human. Significantly change conformacional que.se induces after binding to calcium and pH slightly acidic in the domain III of the anexinas recombinants and that translates into greater exposure of Trp 187. This change also comes after the union to fosfatidilserina of vesicles in the presence of calcium, bearing in mind that this binding capacity to vesicles is the main characteristic of anexinas, has determined the value of Kcty the average number of phospholipids affected by the interaction and has analyzed the influence of the concentration of calcium in the process. AdicionahnenÚ; has been studied iacapacidad of these proteins to induce aggregation devesículas, noting that unlike the anexina A.5humana, laanexina A5 chicken is able to add vesicles via a mechanism mediated by interactions proteína-proteína, where the extreme N-terminal play a key role. Moreover, the study has addressed one of the lesser-known functional aspects of anexinas, their relationship to processes of proliferation, differentiation and malignant transformation. This has been used as a model system I several cell lines colon adenocarcinoma, induciéndose its differentiation through various channels, which has permitidoestableceruna relaciónentrela diferenciacióncelulary the incrementode the expresiónlas anexinas analyzed (Al, A2, A5 and A13). Along with the changes in the expression of these proteins has been analyzed their subcellular localization, which was amended following exposure to butyrate acquiring the anexinas stained cytoplasmic granules and structures associated with membranes, further increasing the secretion of these proteins. REQUIREMENTS FOR PEPTIDE FUSION PROTEIN FUNCTIONALITY F RESPIRATORY SYNCYTIAL VIRUS HUMAN VRSHAuthor: MARTÍN LORENZO DIANA. Year: 2004. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: FACULTAD DE BIOLOGÍA , UCM..
Summary: The human respiratory syncytial virus (VRSH) is the major causative agent of severe infections of the lower respiratory tract in infants, the elderly and immunocompromised adults, producing and neumonías bronchiolitis. The VRSHpertenece the Paramyxoviridae family and gender Pneumovirus. The genome VRSHestá consisting of a single molecule RNAde polarity negative, not segmented that encodes 11 proteins vírales. The protelna F of human respiratory syncytial virus fusion half of the viral and cell membranes. Type I is a glycoprotein which is synthesized as a precursor inactive (FO), which then undergoes a double cut proteolitico resulting in two strings (F1 and F2) held together by disulfide bridges. Prepared protein F FTM- (devoid of the transmembrane region) overlooking the electron microscope, two possible conformations: cones and rods with globular head. In the case of protein FTM-, cones forms are not aggregated and the straw-headed globular are added in the form of rosettes. The treatment of this protein with tripslna ago that only appear rosettes formed by rods with globular head. This structural change is due to double processing of the precursor is not the case eficentemente inside the cell. The aggregation of the protein FTM-probablemente occurs by ínteracciones among péptídos of fusíón molecules FTM-que are exposed after proteolítico complete processing. Because exposure of peptide fusion is a key event in the process of membrane fusion, the changes associated with the processing FTM-serian a good reflection of what happen in the F protein after their activation for the fusion of membranes . In order to study in detail the requirements of peptide fusion for ios changes associated with the processing of the protein Fm- and membrane fusion, introduced a series of mutations in this part of the molecule. When mutations were introduced Gross deletions or amino acid substitutions that alter the character of specific chemical residue peptide fusion is inhibited aggregation of the protein FTM-tras processing proteolítico without changing significantly the hydrophobicity of peptide fusion. In addition, these mutations prevented change conformacional in protein after full processing, permeneciendo in the form of non-aggregated individual cones. These results indicated that a peptide fusion asset for the existence change conformacional in protein FTM- after activation pordoble processing proteolitico. When the same mutations were introduced into the F protein was tested by experiments training síncitlos, only mutations that impidíeron change conformacional after twice cutting FTM- inhíbieron training síncitios. These results indícan that, in addition to the hldrofoblcidad, there are requirements in the sequence peptide fusion for actívación of protein F VRSH.Esto consistent with the high sequence conservation of peptide fusion of different pneumovirus compared with other regions hydrophobic the protein F GENE THERAPY FOR MODULATION OF THE VASCULARIZATION AND HEALING PROCESSES IN NEOPLASIA.Summary: The process of angiogenesis is a generation of new capillaries sanguíneos.En adults, the level of proliferation of céluclas endothelial is very low compared to that of other cell types present in the organismo.Una exception fisiologíca to this rule, esla wound healing . angiogenesis is a critical event in the process of repairing skin, and that the deterioration of the responsiveness angiogénica is a determining factor for the failure of healing in his conjunto.Por other hand, growth and tumor formation metastases are pathological processes, as well as healing, depend heavily on the success with the establishment of angiogenesis for evolución.Así, the existence of an extensive network of capillaries that provide oxygen and nutrients to the tumor, it is essential for growth . In the present work, has explored the possibility of modular through, strategies for gene transfer, the process of angiogenesis, estimulándo in the context of healing or reprimiéndolo during tumor development. ASSEMBLAGE FLSZ OF PROTEIN ESSENTIAL COLI BACTERIA IN THE DIVISION: THE EFFECT OF CROWDING MACROMOLECULARAuthor: GONZÁLEZ IZQUIERDO JOSÉ MANUEL. Year: 2004. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE CIENCIAS QUÍMICAS. Place of preparation: CENTRO DE INVESTIGACIONES BIOLÓGICAS CSIC MADRID.. Summary: In this Report Doctoral thesis has been used to simulate the experimental conditions osmolarity and agglomerate atmosphere of bacterial cytoplasm to study the assembly of protein essential for cell division in E. coli FtsZ. FtsZ (40 Kda), in the presence of GDP, is a weak tendency to oligomerizar in diluted solutions containing concentrations appropriate osmolitos fisiológicos.Sin embargo in the presence of GTP, FtsZ join in a cooperative manner to form dynamic thin filaments relatively small (1 - 2 10-6Da). The agglomeration favors macromolecular assembly GTP-dependiente of FtsZ in two-dimensional polymer dynamic desensamblan after exhausted GTP.Las images of atomic force microscopy revealed that these polymers adopt the structure of tapes of a subunit high. Compared withthe FtsZ filaments observed in vitro in the absence of aglomeraciónn macromolecular, the tapes show a delay and decreased activity GTP handle and a decline in the exchange of GTP within the polymer. We propose that in the cytoplasm agglomerate bacterial and conditions that promote the assembly, the FtsZ filaments tend to align spontaneously formed tapes dinámicas.Estas structures could form part of the Z-ring that is formed in the septum bacteria at the time of division bacterial cell, without the need for additional specific interactions. We call that in resting cells (no-división), there should be regulatory mechanisms that prevent the assembly of the FtsZ tapes (and the ring Z), which would prevent the formation of the septum untimely cycle division. CARRIERS HETEROMÉRICOS AMINO ACID ANALYSIS MUTACIONAL OF RBAT IN CISTINURIA AND STUDIES REGARDING ESTRUCTURA-FUNCIÓNAuthor: JIMÉNEZ VIDAL MAITE. Year: 2004. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAD DE BIOLOGÍA. Place of preparation: CGMM - INSTITUT RECERCA ONCOLÓGICA DEPTO. BIOQUIM Y BIOL. MOLECULAR - UNIVERSIDAD DE BARCELONA. Summary: The conveyors heteroméricos amino acid (HAT) are formed by a slight subunit (LSHAT) and a heavy subunit (HSHAT) interconnected by a disulfide bridge. We have described two HSHAT; rBAT and 4F2hc. They membrane glycoproteins type II, with an N-terminal intracellular end, a single domain trans-membrana and an extreme C-terminal extracellular counterpart to alfa-amilasas. So far we have identified 9 LSHATS: 6 join 4F2hc to give rise to functional transporter (LAT-1, LAT-2 and LAT-1 and + and + LAT-2, asc-1, xCT) joins to rBAT (bo & TA) and two members "orphans" (asc-2, AGT-1), which did not interact with the HSHATs described and perhaps join HSHATs yet to be identified. Different LSHAT the following structural and functional characteristics in common: 1-They are highly hydrophobic proteins glicosiladas not. 2-They have a prediction of structure 12 segments trans-membrana with N and C-terminal ends intracellular. This topology has been demonstrated to the subunit slight xCT, which also presents a reentrant-loop between segments trans-membrana 2 and 3, with functional evidence of its proximity to the path of translocation of the substrate. 3 - The conserved cysteine residues involved in the formation of disulfide bridge is located in the putative extracellular domain II. 4-They need the coexpresión of HSHAT to reach the plasma membrane in a heterologous expression system. 5-confer specificity of the transport complex heteromérico, representing a wide variety of substrates and coupling ions: large neutral amino acids (LAT-1, LAT-2), small (asc-1, LAT-2), loaded negatively (xCT) and basic and neutral amino acids (y + LAT-1, and + LAT-2 and bo, AT +). 6-They behave as mandatory exchangers with a estequiometría 1:1 and with an apparent affinity for the intracellular substrate much lower than the extracellular except for the case asc-1/4F2hc, and perhaps asc-2, it behaves like a exchanger not mandatory. 7 - The LSHAT is able to mediate transport in the absence of the heavy subunit is achieved when expressing surfaces, as occurs in a reconstituted system. RBAT (encoded by the gene SLC3A1) and bo, AT + (encoded by the gene SLC7A9) form system bo, +, which carries basic and neutral amino acids. Defects in this system of transport caused cistinuria. The cistinuria (OMIN 220100) and a hereditary disease, autosomal recessive, caused by the defect in the intestinal absorption and reabasorción renal basic amino acids (lysine, arginine, ornithine), and cystine. Because of their low solubility, cystine precipitates forming calculations along the urinary system. Calculations cause obstruction, infection and, ultimately, kidney failure. Mutations in SLC3A1 cause cistinuria Type I (recessive complete: heterozigotos no hiperexcreción amino acid), and mutations in SLC7A9 cause cistinuria non - I (recessive incomplete: heterozigotos hiperexcretan four amino acids to a lesser extent than the homozigotos cistinúricos and rarely come to develop calculations). This thesis has done an analysis mutacional of rBAT (SLC3A1) in families cistinúricas, and studies regarding estructura-función with LSHATS bo, + AT and xCT. Due to overlapping phenotypes found in carriers with mutations in SLC3A1 or SLC7A9, has created a new classification of cistinuria based on genetic data. Studies relationship estructura-función have led to the identification of a waste in xCT (C327) near the place of union and / or translocation of the substrate, and the determination of the functional unit minimum xCT and bo, AT +, 8 formed 293 for a single subunit lightly. With these results and with the knowledge we have of this family of transporters, we propose that a light subunit coexist asymmetrical translocation of two tracks, one for the influx, and one for the flow. MOLECULAR ADAPTATIONS INDUCED BY EXERCISE RESISTANCE IN CORAZÓN.PREVENCIÓN OF ISCHEMIC DAMAGE.Author: MORÁN BERMEJO MARÍA. Year: 2004. University: COMPLUTENSE DE MADRID [ www.ucm.es]. Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS. Place of preparation: FACULTAD DE BIOLOGÍA UCM.. Summary: SUMMARY: The achievement of physical exercise on a regular basis induces a series of adaptations of the heart that lead to individuals who are physically active have a lower incidence of cardiovascular disease and a lower mortality from such diseases. The molecular basis of the cardioprotección by the exercise are not known clearly. Modificacioners of various cellular systems have been implicated in such cardioprotección increases the antioxidant capacity of the myocardium, increases in the levels of expression of heat shock proteins (HSP), and adjustments to the regulatory systems of calcium. On the other hand, some authors have proposed that conducting exhaustive exercise can cause cardiac damage. With the completion of the exercise in endurance events, a phenomenon that has been widespread among recreational athletes in recent years, can have a negative impact on the hearts of popular athletes. In this thesis has dealt with the study of molecular adaptations that expeñmenta myocardium of rats trained in rolling tapestry, and its role in the phenomenon of cardioprotección front of the process isquemialreperfusión. Also addressing the analysis of possible damage cardiac empeñmentado by corridors of Marathon popular Madñd in the years 1997 and 1998. The results showed some adjustments to regulatory elements calcium and antioxidant defense system in the myocardium of rats trained for 24 weeks. Also, there was a better metabolic recovery in the hearts of rats trained subjected to ischemia / reperfusion. The results obtained in studies of injury cadiaco in humans showed that the realization of comprehensive exercise by deportitas young and old healthy, does not cause any heart damage. CLONING, SEQUENCING AND CHARACTERIZATION OF THE GENES ENCODING SYSTEM ASSIMILATIVE REDUCTION OF NITRATE IN RHODOBACTER CAPSULES E1F1.Author: PINO OSUNA CARMEN MARIA. Year: 2004. University: CÓRDOBA [ www.uco.es]. Place of defense: FACULTAD DE CIENCIAS. Place of preparation: FACULTAD DE CIENCIAS. Summary: The bacteria fototrófia Rhodobacter capsulatus E1F1 has a system for reducing the rate assimilative nitrate, which is induced in the presence of nitrate / nitrico and negatively regulated by amonio.Mediante using assimilative type, which is induced in the presence of nitrate / nitrite and regulates negatively by ammonium. Using degenerate oligonucleotides has been amplified by PCR from 0.4 Kb a fragment of the gene nasA R. Capsulatus, which has been used as a probe for screening of a genomic library, which has allowed the identification of two cósmidos containing the region cf. The sequencing and analysis of approximately 17kb for the exogenous DNA of one of these cosmic has revealed the presence of 14 genes, most related to the assimilation of nitrate and nitrite. The region includes dg sequenced genes regulators nasT, nasS and nsrR. Three genes would be involved in the transport of nitrate / nitrite: nasF codify the componenete genes periplásmico, nasE the integral membrane and nasD subunit citoplásmatica with ATPase activity. Following these genes are located genes structural nasA, nasB and nirD encoding enzymes nitrate and nitrite. The gene cysG involved in the synthesis of sirohemo and gene moaD involved in the synthesis of cofactor of molibdopterina and guanine also located in this regién. The gene chrA codify a protein homologous to a chromate and transporter gene nnrS a protein menbrana that problamemente involved in the taxi toward nitrate. Lastly, in this region also located the gene hcp coding for a possible hybrid protein center. Physiological function of this protein has been an enigma until recently it has been shown that the protein of E. coli HCP has hydroxylamine reductase activity. By RT-PCR and hybridization Northerm has shown that the structural genes of nitrate reductase enzymes and nitrite reductase genes of nitrate transport system and the gene cysG is contranscriben under certain metabolic conditions, along with the regulatory genes nsrRnasTS. By contrast, genes hcp, chrA and nnrS are monocistrónicos. INTERACTION BETWEEN PEPTIDES DERIVED FROM PROTEIN GP41 AND PRPC SYSTEMS MODELS BIOMENBRANAS.Author: PASCUAL MARTINEZ ROBERTO. Year: 2004. University: MIGUEL HERNÁNDEZ DE ELCHE [ www.umh.es]. Place of defense: INSTITUTO DE BIOLOGÍA MOLECULAR Y CELULAR. Place of preparation: INSTITUTO DE BIOLOGÍA MOLECULAR Y CELULAR. Summary: The fundamental objective of this work is to understand the molecular interactions that take place between different components of the biomembranas and more specifically, between different proteins and paptidos consistemas model membrane. The paptidos selected for the study were three pieces paptidicos of glycoprotein Gp41, a fusion protein that is found in the shell of the human immunodeficiency virus (HIV) and a fragment of the protein prions PrPc. The thesis is divided into two clearly separate chapters, some of them focused on the role of the different fragments of Gp41 during the process of fusion of the virus and the other in the study of the fragment peptidico the PrPc and suposible involvement in the mechanism of toxicity . For the study of the two systems has been used a similar methodology. In each case has been marked degree of peptide interaction with the lipid membrane and the disruption of the same using different biophysical techniques, such as infrared spectroscopy, fluorescence spectroscopy and differential calorimetry neighborhood. The use of all these metoldologías has allowed the distinguishing characteristics of the molecular effect of different peptides on the organization and stability of the bilayer lipída and how its correlation with the potential structural changes in the protein. The results show that the fragments peptídicos of Gp41 interact preferentially with anionic lipids and that this interaction induces a change conformmacional in peptides and destabilizes the membrane. These results support the hypothesis that these regions of the protein parcipan an active role in the mechanism of fusion of the viral and cell membranes. Regarding the fracmento peptídico of PrPc results indicate that paptido has a high affinity for all types of membranes localizándose preferably near the surface and changing its shape. SERUM TUMOR MARKERS IN SQUAMOUS CELL CARCINOMA OF HEAD AND NECK CLINICAL VALUE OF THE ACTIVITY OF THE ENZYME LL-FUCO-SIDASA AND ACID SIALICO TOTAL AND ABOUT PROTEINAuthor: GONZÁLEZ GACIO GLORIA. Year: 2004. University: VIGO [ www.uvigo.es]. Place of defense: FACULTAD DE BIOLOGIA. Place of preparation: FACULTAD DE BIOLOGÍA. UBIQUINONE BIOSYNTHESIS GENES IN CAENORHABDITIS ELEGANS DEVELOPMENTAuthor: ASENCIO SALCEDO CLAUDIO. Year: 2004. University: PABLO DE OLAVIDE [ www.upo.es]. Place of defense: FACULTAD DE CIENCIAS EXPERIMENTALES. Place of preparation: FACULTAD DE CIENCIAS EXPERIMENTALES. Summary: The coenzyme Q is a lipid isoprenoide involved in the electron transport to the mitochondrial respiratory chain. This lipid serving in the defense against oxidative stress as well as in controlling the proliferation celular.La synthesis ubiquinona has been studied in organisms procariotras such as Escherichia coli and in unicellular eukaryotes, such as Saccharomyces cerevisiae. The work has studied the regulation of synthesis of coenzyme Q in an animal model, namely the nematode Caenorhabditis elegans. Over the study have identified the genes involved in the synthesis of coenzyme Q in the nematode, as well as their influence on the oxidative stress and envejecimiento.Se has studied the role of these genes by functional complementation of mutant in the synthesis the coenzyme Q in the yeast S. Cerevisiae. Furthermore, we have studied the regulation of the expression of genes synthesis of coenzyme Q using mergers of genes synthesis Q with GFP (green fluorescent protein). This tool has made it possible to know the pattern of expression of these genes along the development and aging of C. Elegans and deduct their possible mode regulación.Igualmente, has been characterized mutant coq-8 (ok840) of C. Elegans, which is deficient in the synthesis of ubiquinona.Como result of these studies provides a model for regulation of the synthesis of ubiquinona in development and aging of C. Elegans. ANÀLISI BIOINFORMÀTICA OF THEM MUTACIONS PUNTUALS PATOLÒGIQUESAuthor: FERRER COSTA CARLES. Year: 2004. University: BARCELONA [ www.ub.es]. Place of defense: FACULTAT DE BIOLOGIA DE LA UNIVERSITAT DE BARCELONA. Place of preparation: DEPARTAMENT DE BIOQUÍMICA I BIOLOGÍA MOLECULAR.
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