LIFE SCIENCES, 8

Author: LUCAS GAY MARIA JESUS.
Year: 2005.
University: CANTABRIA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The relaxasa is the protein responsible for the initiation reactions in the processing conjugativo DNA. The relaxasa recognizes and cuts a link fosfodiéster specific located at the origin of transfer by the attack nucleofílico a tyrosine. This paper has studied the recnocimiento DNA and biochemistry of the reaction catalyzed by DNA cutting the relaxasa of plasmid R388, TrwC. The fragment TrwC-N293, containing the first 293 amino acids of the protein, binds oligonucleotides in the region cutting, nic, which include repetition inverted IR2 with an affinity nanomolar. This union involves a protein molecule and DNA. The three-dimensional structure of this complex is built on two layers alpha / beta and has a crack where the center is active. The structures available show that the union of TrwC-N293 the DNA is associated with a folding of the protein. The affinity of the union of TrwC-N293 by nic region is determined by its interactions with the first 22 nucleotides in the direction of 5 'to the site nic. Contacts with the double chain of inverted repeat are showing a greater contribution to the affinity of the union. The union of the stream near the nic in the form of simple chain shows lower affinity, but its recognition is essential for the proper positioning of DNA in the center assets, so that it could carry out the attack nucleofílico on phosphate court. This different affinity that TrwC will suggest contacting the first sequence IR2 and this union will facilitate the recognition of the adjacent sequence (bases between IR2 and nic site and two bases 3 'nic). These two regions of DNA are specifically recognized by TrwC, so that both interactions will help the relaxasa discern among other sequences, and its target, the site nic of oriT of R388. A study of the mutants waste deTrwC Arg81, Ser89 and Lys92 has shown that its function is related to their interaction with DNA. The results suggest that R81 facilitates desapareamiento of double chain around nic, S89 interacts with the extreme 3 'DNA and K92 aid cut to the proper positioning of DNA in the active center. It also has studied the role of metal ions in the activity TrwC. On the one hand, the metal ions have a role in catalysing the reaction of court, and that from the position of the metal ion in the active center of the structures resolved TrwC reveal that the metal ions pocionan and polarize the phosphate court. Moreover, it has been shown that they also have a structural role, as the union of metal ions Mn and Ni makes the folding of the protein is more compact. Finally, it has been analyzed residues TrwC addition to the tirosinas Tyr18 and Tyr26 involved in the mechanism of the reaction cut DNA. A study by mutagenesis to alanine has revealed that the waste Asp85, His 150, His 161 and His 163 contribute to attack nucleofílico by Tyr18 and Tyr26. The triad of histidinas coordinate the metal ion, which is essential for the reaction, and it has been proposed that Asp85 activates the hydroxyl group of Tyr18 by abstraction of a proton.

Author: QUINTANA BUSTAMANTE OSCAR.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: The presence of hepatocytes derived from the bone marrow (HDMO) in the liver has been described in different models. The mechanism involved in its origin is not entirely clear. It has been suggested as possible mechanisms of direct differentiation hematopoietic stem cells (CMHs) and / or cell fusion between cells derived from CMHs and endogenous hepatocytes. The frequency of HDMO is related to the model studied, and varies according to the source from the 30% of hepatocytes to be a phenomenon very low. To study the process of generating HDMO, has developed a mouse model, in which female mice letalmente irradiated cells were transplanted with MO male transgenic mice, expressing green fluorescent protein (EGFP) controlled by the ubiquitous promoter the b-actina. After the establishment of hematopoiesis chimerical, animals were injected with saline or carbon tetrachloride (CCl4) to induce liver damage similar to a cirrósis chronic. In animals treated with CCl4 there was a big difference in the plasma parameters and structure completely altered liver. The HDMO were identified by immunofluorescence as EGFP + cells with morphology liver, liver specific proteins expressing and not expressing hematopoietic markers; frequency HDMO in livers damaged was 1 per 250,000 hepatocytes totals. Subsequently, was mobilized for three weeks with the colony stimulating factor (G-CSF) or granulocyte with G-CSF/Trombopoyétina (TPO) to half the animals in each group. A week later, the animals were sacrificed and examined the presence of HDMO. The mobilization with G-CSF significantly increased the percentage of HDMO (over 17 times) in the livers of animals treated with CCl4. An equal frequency was reached with the mobilization with G-CSF/TPO. Numbers similar HDMO were detected when the mice were transplanted with a purified population of CMHs (phenotype Lin-/Sac-1 + / c-Kit + / EGFP), which needed a bone marrow graft prior. The analysis of the mechanisms involved in generating HDMO, was conducted by colocalización markers from the donor female MO (EGFP) and the recipient mice male (Y chromosome). It found that the majority of hepatocytes expressing EGFP also had the Y chromosome, indicating that its origin was the result of a merger between hepatocytes in vivo and endogenous blood cells of the female. This process was increased using ammonium chloride (NH4Cl), an inhibitor of phagocytosis, suggesting that the processes endocíticos characteristic of monocítos-macrófagos, were implicated in the formation of HDMO. Finally, to determine the manner in which the nucleus hematopoietic is reprogramaba were analyzed qualitatively and quantitatively morphology and the expression of nuclear antigen-specific lineage. We identified a sequential process, through which the nucleus hematopoietic changed its morphology, lost nuclear hematopoietic factors and finally acquired nuclear factors liver, equalizing the nuclei of the hepatocytes. In summary, we have shown that: i) the presence of HDMO in the liver occurs when there is a liver damage. Ii) The presence of these cells can be increased significantly with the use of hematopoietic growth factors. Iii) The origin of HDMO is haemopoietic and is produced by fusion in vivo between hematopoietic cells and hepatocytes. Iv) The core hematopoietic of HDMO unchanged at its morphology, gene silencing hematopoietic markers and presents nuclear liver.

Author: BENITO GARZÓN MARTA.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE CIENCIAS, DEPARTAMENTO DE BIOLOGÍA.
Place of preparation: UNIVERSIDAD AUTÓNOMA DE MADRID, DEPARTAMENTO DE BIOLOGÍA.

Summary: Different distributions of 19 tree species in the Iberian peninsula in relacción climate. It creates a framework for modeling environment open source oara predicting habitat of the species. This framework encompasses three learning techniques automatic data: classification and regression trees, neural networks and the algorithm of random forest. It predicted distributions of these species to different climate scenarios: the last glacial maximum (LGM, 21000BP), the Climate Optimum (6000BP), this, 2020, 2050 and 2080. Climate scenarios were adapted for the Iberian peninsula from General Circulation Models Atmospheric (JAG). The results for the last show as the areas of distribution of species in the LGM plotted shelters flora highlighted through palinología and filogeografía. The results also show an increase in range species that suffered during the Climate Optimum. In the future, the general trend in the distributions of species for any of the climate scenarios and storylines of the IPCC (A1, A2, B1 and B2) is a severe decline in the areas of occupation as a response to climate change. The group of species that is most dramatically affected in terms of reduction of area is composed of species submediterráneas, which would avocadas in some cases almost to extinction. The coniferous forest mountain patent also suffer a decline in their distribution areas. This would not be so strong in the case of forests planocaducifolios. The Mediterranean forests show a mayuor ability to move as a response to climate change than other types of forests. The species that live in the areas most continental suffer a very sharp decline due to rising temperatures that will occur in most continental areas.

Author: Barrio Burgos Jorge.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Centro Nacional Biotecnología.
Place of preparation: Centro Nacional de Biotecnología.

Summary: The DREAM protein (Downstream regulatory element antagonist modulator) protein regulates gene expresion by direct binding to DNA in a Ca2+-dependent manner. To investigate the function of DREAM in vivo, we have prepared and characterized several lines of transgenic mice which overespress a calcium insensitive EF-hand mutant DREAM (EFmDREAM). Both in vitro and vivo, EFmDREAM functions a dominant active mutant (daDREAM) blocking calcium-mediated de-repression of target genes. Overexpression of daDREAM in the CNS resulted in an increase of the nociceptive response in several pain models. This findig correlates with the the important reduction in the opioid tone in daDREAM mice with a significant decrease in the expression of all three opioid receptors as well as dynorphines. Comparative gene profiling analisys of daDREAM revealed important differences in genetic response compared with wild type mice. The pattern of gene expression in daDREAM is similar to the chronic pain model gene expression pattern.

Author: JOHNSTONE ESPAÑA CAROLINA.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: The respiratory syncytial virus (RSV) man is one of the major causes of respiratory infections in infants and the elderly. The fusion glycoprotein (R) VRS is a target antigen in the development of vaccines and that triggers an immune response mediated by antibodies and cytotoxic CD8 & T lymphocytes (CTL). The protein F of the strain A2 VRS have described two of CTL epítopos murine restricted by H-2Kd, epítopos F85-93 and F92-106. In order to study the immune response compared with the RSV F protein mediated by CTL, in the mouse model of BALB / c, were generated in vitro lines CTL polyclonal specific protein F through procedures that kept monoespecíficas or multi. In the second case has been used in a novel stimulation with cells BCH4 persistently infected with the strain Long VRS. CTL lines were used in functional testing of antigen presentation by citotóxicidad or intracellular cytokine staining (ICS). In addition, to evaluate the response in vivo CD8 + T cells were carried out tests ICS splenocytes with ex-vivo. The most relevant results are as follows:-protein F of the Long strain of RSV, is retained epítopo F85-93 submitted by Kd and described on the strain A2. However, there is no evidence of the presence of epítopo F92-106 in strain Long. - The sequence F249-258 of protein F of the strain Long VRS is a new epítopo submitted by Kd to CTL as nonámero (TYMLTNSEL) or decámero (TYMLTNSELL). The infection in vivo mouse BALB / c with RSV or with a recombinant vaccinia virus that encodes a protein F VRS (vvF) induces CTL meet this epítopo. In the immune response in vivo mediated by CD8 + T cells in mice BALB / c infected with vvF, is establishing a inmunodominancia of F85-93 on F249-258, with the line polyclonal multi CTL F/BCH4 representative of this pattern inmunodominancia . - Epítopos of the F protein VRS F85-93 and F249-258 submitted by Kd are processed by different ways depending on the epítopo, in the form of protein F, and background virus. Both epítopos may be submitted by different pathways independent of TAP. The results presented in this thesis contribute to the study in murine models of the role of CTL in the immune response to protein F VRS, and emphasize the diversity of processing routes available for tabling epítopos by MHC class I CTL.

Author: Medina Vico Pedro Pablo.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Cen. Nac. de Inv. Oncol.(U.A.M).
Place of preparation: Cen. Nac. de Inv. Oncol.(U.A.M).

Summary: Lung cancer now is a serious health problem in Spain is the first cancer in terms of mortality and the second in terms of incidence. This thesis from different angles contributes to the advancement of molecular biology of lung cancer, a tool that can assist in the decline in these statistics: On the one hand has studied the relationship between polymorphisms in genes of repairing damage to the DNA (linked the carcinógenes of snuff), and genetic and pathological features of primary lung tumors. Finally, it has conducted a search of oncogenes activated by gene amplification in lung cancer, which may be a potential target for therapeutic treatment.

Author: ALONSO LOBO JUAN MANUEL.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: DEPARTAMENTO DE BIOLOGÍA MOLECULAR.
Place of preparation: INSTITUTO DE SALUD CARLOS III (MADRID).

Summary: THE GOAL OF THIS WORK IN A PRICIPIO WAS THE REGULATORY REVIEW OF PROMOTER OF CXCL12 IN CELLS PRODUCTION CONSTITUENT: LC5, MS5 AND U373, AND DETERMINE WHETHER FOR STIMULATING THE INDUCCIÓN, REGULATIONS AS THE REGIONS IMPLIED IN SUCH REGULATIONS OF THE PROMOTER. IN ONE PART, THE GOAL WAS ANALYZING THE EFFECT OF TAX OF PROTEÍNA HTLV-1 ON THE EXPRESSION OF CXCL12 IN LINFOCITOS, AS WELL AS IN T CELLS OF LEUCEMIAS / LINFOMAS ASSOCIATED WITH AN INFECTION HTLV-1. SE OBSERVÓ TO AN EXPRESSION OF THE TRANSITIONAL PROTEÍNA TAX IN CELLS JURKATT PRODUJO AN IMPORTANT TRANSACTIVACIÓN OF PROMOTER OF CXCL12. AGREE TO THESE RESULTS, SE OBSERVÓ THE PRESENCE OF WHETHER AS mRNA PROTEÍNA IN CELLS MT2 (LINE CELLULAR INFECTADA FORM BY THE CHRONIC HTLV-1); THAT ALL SEEN BY RT-PCR, CITOMETRÍA FLOW AND MARCAJE BY INMUNOFLUORESCENCIA. CXCL12 WAS DETECTADO ALSO IN THE SOBRENADANTE CELL MT2 BY ELISA TECHNIQUES AND CHEQUEADA ITS ACTIVITY FOR FUNCTIONAL TESTING OF QUIMIOTAXIS. BIOPSIAS OF PATIENTS INFECTADOS WITH HTLV-1 MOSTRARON LINFOCITOS CD3 + POSITIVE FOR EXPRESSION OF CXCL12, WHILE NOT APARECÍA THIS GANGLIA LINFÁTICOS OF EXPRESSION IN PATIENTS NOT INFECTADOS THE HTLV-1. BASED ON THESE RESULTS THAT MAY BE CONCLUIR PROTEÍNA OF TAX HTLV-1 INDUCE THE EXPRESSION OF QUIMIOCINA CXCL12 LEVEL TRANSCRIPCIONAL, SHOW UP WELL AN EXPRESSION ABERRANTE OF PROTEÍNA CXCL12 BOTH LINES IN CELLULAR INFECTADAS WITH HTLV-1 AS IN LINFOCITOS OF BIOPSIAS FROM LINFOMAS ASSOCIATED WITH THIS VIRUS. THE INCREASE IN THE EXPRESSION OF CXCL12 BY INFECTION HTLV-1 CAN CONTRIBUTE TO THE RECRUITMENT OF LINFOCITOS HEALTHY UP GANGLIA INFECTADOS THE HTLV-1, INDUCIENDO WELL THE SPREAD OF INFECTION.

Author: Muñoz Risueño Ruth.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Fa. de Cien. Secc. Biol.Biol. Molec..
Place of preparation: Facultad de Ciencias.

Summary: The activation of the receptor for antigen (TCR) T cells can produce different answers depending on the nature of the antigenic peptide framed in the major histocompatibility complex (MHCp). This implies the potential combination of the ligand specificity of the TCR and the activation of different intracellular signaling cascades. The molecular mechanism that allows the discrimination is known in part. The monoclonal antibody APA1 / 1 recognizes a epítopo in cytosolic stem from CD3e set out when the TCR is fully activated. Exposure of epítopo of APA1 / 1 occurs promptly and independently of the activity tirosín-quinasa-in fact, this exhibition is produced when cells are stimulated to 0Â ° C. Only the stimulation of the TCR with the agonist ligand induces strong exposure epítopo of APA1 / 1. In most of the resting T cells in lymph nodes, epítopo of APA1 / 1 is not exposed, but after injection of antigen in vivo, epítopo outlined in the majority of T cells specific for the antigen. These results show that the TCR undergoes a change conformacional after the union of MHCp in vitro and in vivo, and a stable molecular correlation with the production of TCR activation. A unique feature of TCR is its ability to explore the ligands MHCp structurally similar and transmit biochemical signals differentially depending on the strength of the ligand recognition. In developing thymocytes, the weak ligands induce positive selection and ligands induce strong negative selection. A minority of non-transgenic mouse thymocytes exposed the epítopo recognized by APA1 / 1. The cells APA1 / 1 positive are DP are in the crust and unions cortico-medulares and are in contact with the epithelial cells and dendritic. The population APA1 / 1 positive increases in terms of negative selection in both the TCR transgenic mice restricted to MHC class I or class II. The majority of thymocytes APA1 / 1 positive are TUNEL positive, indicating the existence of a direct correlation between exposure epítopo of APA1 / 1 and the induction of apoptosis mediated by ligands MHCp that induce negative selection. Although there is evidence experimental change conformacional in CD3e after stimulation of TCR, it is not known how transmission of antigenic recognition from subunits reconocedoras of ligand TCRab the signaling subunit of CD3. The TCR stimulation induces protection against digestion with proteases in the stalks CD3e and CD3z. Using a thermodynamic approach, describes the properties of the active and non-active conformation of dimers of CD3. Finally, we propose a model in which the stimulation of TCR triggering rigidificación the structure and compaction of the stems of CD3.

Author: VANDERMEEREN Andrée Marie.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Departamento de Biología Molecular.
Place of preparation: Centro Nacional de Biotecnología (CSIC).

Summary: The hepatitis C virus (HCV) is the causative agent of non-A and non-B hepatitis WHO estimates that 3% of the world's population is clinically affected by this virus. More than half the cases progress to chronic infections that often develop cirrhosis of the liver that can evolve to hepatocellular carcinoma. However, the mechanism of pathogenesis is still little known because of the absence of a cell culture system and a model suitable for viral infection and replication of the virus. The vaccinia virus (VV) has been a widely used vector for the expression of heterologous proteins, we have developed a new expression system based on a recombinant virus vaccinia virus, and we call VT7-HCV7.9. This recombinant virus expressing inducible form of structural proteins (Core, E1 and E2) and non-structural (NS2, NS3, NS4A, NS4B, NS5A and part of NS5B) ORF subtype 1b of HCV. Analysis by confocal microscopy and Western blot showed that the viral polyprotein is efficiently processed in different cell lines (Hela, BSC40 and HepG2) infected with recombinant virus VT7-HCV7.9, speaking different protein structural and non-structural HCV. Moreover, we have seen that HCV proteins expressed from VT7-HCV7.9 are located exclusively in the cytoplasm with a distribution puntuada, colocalizan with the endoplasmic reticulum (ER) and mitochondria and produces break Golgi apparatus. In studies miscroscopía electronic human cells infected with recombinant viruses, it was noted that HCV proteins induce changes in the architecture of the infected cells characterized by the loss of the organization IR, swelling of mitochondria, training network membranes and electron dense structures in the network membrane, scattered in several areas. The changes are similar to those seen in liver cells from chimpanzees infected with HCV. Moreover, the induced expression of HCV from VV, causes inhibition of total protein synthesis in human carcinoma cells, Hela, and liver, HepG2, phosphorylation factor initiation eIF2alfa. This expression also affects the vaccinia virus replication. We have shown that the protein quinaza induced IFN, PKR, is the main kinase responsible for the phosphorylation of eIF2alfa and inhibition of translation in cells infected with VT7-HCV7.9. We also note that the expression of proteins in HCV infected cells with VT7-HCV7.9 induce apoptosis dependent on caspase (caspase-3, -8 and -9) and mediated by the mitochondria. In addition, the apoptosis is mediated by the system 2-5A synthase / RNasa L independently PKR. Finally, we note that cell death by apoptosis may be associated with the expression of proteins E1-E2 and NS5A virus HCV. These results indicate that expression system HCV genome by recombinant VV can facilitate knowledge about viral morphogenesis and their relationship with the huésed.

Author: CAÑADAS CARBÓ ANA MARÍA.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: The overall aim of the thesis was to contribute to the conservation of whales in the Alboran Sea, through the study of their ecology and the proposed management and conservation measures. The study area includes the northern section of the Alboran Sea and the Gulf of Vera. The observation deck was the research vessel Toftevaag. Data were collected transect linear behavior, size of the group and for each other sightings of whales, as well as environmental data and human activities. The first phase of this study, which focused on studying the distribution of seven species of cetaceans in southern Almeria, indicated that the local topography can play a significant role in its distribution. We identified two groups of species according to their distribution with respect to depth. Dolphins listings, pilot whales gray, black pilot whales, whales picudas and sperm whales, show preference for deep water. The common dolphin and hinnies were found more often in shallower water. The feature common to all species in the group of deepwater most obvious is their feeding habits (predominantly teutofágicas). However, common dolphins and hinnies (group shallower water), have shown a preference for fish in many studies of diet. In a second phase would elaborate on the analysis of the habitat preferences of the different species of cetaceans utulizando tool of spatial analysis. The results of these new analyzes basically match for the first phase, but providing them with greater robustness. The common and bottlenose dolphins continue to show the greatest presence in the waters of the continental shelf and the collapse of the platform throughout the region (and especially around the Dry Olives for delfin hinnies). The other five species are distributed primarily by the deep sea, avoiding the continental shelf. Thanks to this work have been able to identify the general pattern of distribution of these species throughout the area, from which there was no prior information. A more specific and advanced study was conducted on the common and bottlenose dolphins, also estimated their abundance. For the dolphin hinnies, abundance estimates for the period 2000 to 2003 in the area of Alboran is 584 dolphins (95% CI = 278-744), mainly concentrated in southern Almeria, the coastal areas of Grenada and south Punta CDAlaburras in Malaga. In the area of Almwería, abundance estimated between 1992 and 1997 fuew of 111 dolphins (95% CI = 54-234). Between 1998 and 200, after the arrival of animals "immigrants", the estimated abundance increased by a factor of four. In 2001-2003, the estimated abundance decreased by half. The central area of higher density was the same in all three periods: about "Dry Olives." The total abundance of dolphin common throughout the study area from Gibraltar to the Gulf of Vera between 2000 and 2004 was estimated at 19428 animals (95% CI = 15277 - 22804): There is a seasonal variation in desidad in southern Almeria with an average density higher in summer than in winter. There are also geographical differences when considering the entire study area during the summer, with a density much higher in the west than in the east, and intermediate density south of Almeria in the downtown area. The population was stable from 1992 to 2004 in the Alboran Sea, while it found a significant decrease in the Gulf of Vera since 1996. Moreover, the groups with crís tend to prefer coastal waters and groups without offspring deeper waters. The groups monoespecíficos followed the general pattern of higher current densities around the fall of the platform, while the highest densities of animals in mixed groups (mixed with dolphin listing) occur in the deep sea. The highest densities of animals feeding occur in coastal waters. The densid 8 Ad what 4f9 s animals on the move follows the general pattern described above. There is a very strong pattern bimodal socializing in groups, with more smaller groups in deep water, and fewer but larger groups in shallower water. The work performed in this study have contributed significantly to the conservation of whales in the Alboran Sea. We have proposed several MSPs: four SCI and SPAMI. We have laid the groundwork for the development of the Plan of Conservation Bottlenose dolphin in Andalusia and Murcia, and has actively collaborated in the elaboration of the Plan of Conservation common dolphin in the Mediterranean sea of ACCOBAMS.

Author: Letizia Annalisa.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Centro de Biología Molecular S. Ochoa.
Place of preparation: Centro de Biología Molecular S. Ochoa.

Summary: The Iroquois Complex (C-Iro) from Drosophila melanogaster is composed of three genes, araucan (plows), caupolican (caup) and mirror (mirr), which codifícan around with homeodomain proteins. These genes are expressed in different domains discs imaginales of Drosophila, epithelial structures of the larva of which originate most of the structures cuticulares the adult fly. The expression of these genes in different domains and characteristic over development is very important as they contribute to the specification of the territories which are expressed and the formation of the patterns that characterize these structures. The genes of C-Iro expressed in domains are very similar, so it was suggested that this feature was due to the presence of some cis-regulatory sequences (or enhancers), which would act simultaneously on the three genes regulándone the transcripición and resulting in Final spatial and temporal patterns of expression identical (in the case of plows and caup) or similar (in the case of mirr regarding plows and caup). In this work we have identified five regulatory sequences, located in the C-Iro between units transcription caup and mirr. None of the 5 fragments isolated mediates the expression of a marker gene (lacZ) as the complete pattern of genes C-Iro in the wing imaginal disc (the system model used in this study), which confirm the original hypothesis the pattern is the result of the joint effort of different enhancers specific territories that represent the full pattern subdomains. One of the regulatory elements analyzed in this work (e-Iro1) directs the expression of lacZ gene in a domain of the disc corresponding to future mesotórax dorsal (notum) of the adult fly, in a manner very similar to the original pattern of genes C-Iro in this territory. Different studies have shown that the expression of genetic genes C-Iro essentially depends on the activity of two signaling pathways: the path of Dpp (Decapentaplegic) and the path of EGFR (Epidermal Growth Factor Receptor). The path of EGFR is activated from the wing disc thank ligand Vn (Vein): This triggers a cascade of events that leads to the activation of cellular transcription factors, which in turn triggered a series of gene targets. It has been seen that these genes are those of C-Iro. On the other hand towards Dpp represses the transcription of genes C-Iro confining its pattern of expression in the region of notum side. The enhancer e-Iro1 containing different DNA binding sites for transcription factors specific effectors of the two tracks mentioned, in particular factor Pointed STD (Pnt) activated by means of EGFR protein and GATA Pannier (Pnr) activated by the route Dpp. Some of these sites are evolutionarily conserved. The functionality of these sites were analyzed in vivo by generating transgenic flies carrying forms mutadas or truncated element e-Iro1 original. Our results indicate that Pnt conducted by the activation of genes C-Iro dependent on the path of EGFR, at least in part, through the element e-Iro1, while the Suppression of these genes in the notum medial, depending on the route of Dpp is due to the activity of repressive dímero Pnr-Ush also through a regulator e-Iro1. In short, thanks to a molecular analysis of the genomic region of C-Iro, we have identified a cis-regulatory sequence responsible for carrying out the regulation of transcription of genes C-Iro, which depends in turn two signaling pathways: the Dpp and the EGFR.

Author: García Marcos Alberto.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Centro de Biología Molecular Severo Ochoa.
Place of preparation: Centro de Biología Molecular Severo Ochoa.

Summary: The stem ribosomal Protuberans side is a very flexible structure in the largest subunit of the ribosome. In prokaryotes, consists of a core protein called L10, and four other proteins that bind called acid in the form of dimers L7/L12. It S. Cerevisiae complexity is higher, since in addition to the core protein called in this case P0, there are 4 proteins ácias different: P1a, P1b, P2a and P2b. Although the majority of experimental data suggest that these proteins bind acid in the form of monomers to the ribosomes, and therefore these follow a homogeneous distribution in the cell, with stems composed of a protein acidic each type. However, certain data intersecting chemical, compared with prokaryotes, and the ability to P2b in solution to form homodímeros, also suggest that there might be a model of heterogeneous composition of ribosomes with different combinations homodímeros of acidic protein. All this is of great importance not only structural but also functional, since according to the acidic protein coupled to ribosome, it has been shown that varies the pattern of proteins that the cell expresses. With the overall aim of clarifying the presence or absence of homodímeros protein acidic in the ribosome, and discriminate between the existence of the model of homogeneous or heterogeneous composition of stem ribosomal, raised a series of specific objectives and techniques. First, they replaced some residue protein acidic protein by cisteínas and conducted experiments intersecting chemical. The results are consistent with a model of homogeneous composition of ribosomal stem, and also show a direct interaction between P2a and P1b. There is also the emergence of homodímeros of P2a (with a mutated to cysteine residue) in strains that have been eliminated P2a endogenous is merely artifact without biological significance, as the reaction of intersecting occurs in the cytoplasm before union of the ribosome, and this pair, only one of the two protein binds directly to the ribosome, while the other does so through its partnership with the priemra, but not an integral part of the stem. The second goal was the analysis of estructra stem in vivo, using a modern technique biophysics, two-photon microscopy associated with fluorescence correlation spectroscopy. It won a series of mutant strains of yeast, which delecionaron well each of the acidic protein individually, or all possible combinations of two acidic protein. It was subsequently merged the green fluorescent protein (GFP) at the carboxyl end of all protein acidic and entered either singly or in pairs, in the appropriate strains of yeast. We actions on cells in vivo, being able to discriminate the presence of one or two acidic protein coupled concurrently with the ribosome. This could set the binding capacity of the various pairs of the ribosome proteins, and found that in the cell, a large majority of ribosomes are modeled homogeneous, with an acidic protein of each type united, but also evident the presence of small subpopulations of ribosomes who follow the heterogeneous model with various combinations of homodímeros. In addition, there was a great dynamism in ribosome binding to the protein acidic and the binding sites for each acidic protein in the ribosome are not absolutely specific and certain conditions a protein can occupy a site that is not your site union specific. The data, together with other results of laboratory and data in the literature, allowed to propose a model for the stem where ribosomal protein type P2 and P0 are with their extreme carboxyl nearby and extended into the cytoplasm, probably charge to stabilize the union transient factors soluble translation, while the protein-type Q1 will see their extreme carboxyl nearby and replegad 8 os on 4ee the body of the ribosome may be responsible for activating the hydrolysis of GTP on factors GTP-dependent translation. Finally, a comparison between the results in vivo and in vitro results obtained after purification ribosomes, show that purification can alter the composition of stem ribosomal and subpopulations that are modeled heterogeneous to be very minority, undetectable. So all in vitro techniques, which involve purification ribosomes, would be entering an important artifact in studies of the composition of stem ribosomal.

Author: Jimenez Mateos Eva María.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Facultad de Biología.
Place of preparation: Centro de Biología Celular "Severo Ochoa".

Summary: Several lines of evidenes have indicates that changes in te structure of neuronal cytoskeleton could be the source of the dramatic morphological changes that occur during neuronal diferentiation. It has been proposed that microtubule-associated proteins can contribute to the development of this phenomenon by controlling the dynamic properties of microtubules. MAP1B is a neuron-specific microtubule associated protein implicated in the control of the dynamic stability of microtubules and in the cross-talk between microtubules and actin filaments. Different MAPs can cotnribute to this maturation. MAP1B and MAP2 are implicated in the first steps of maturation, and MAP1B and Tau are implicated in the neuronal maturation. The signalling cascades governing neuronal migration are believed to link extracellular signals to cytoskeletal components. We have observed that MAP1B could participate in the signalling of molecules, such as Netrin and Reelin, both implicated in the migration of neurons. For neuronal migration to occur, the cell must undergo morphlogical changes that require modifications to the cytoskeleton. Several different microtubule-associated proteins (MAPs) or actin-binding proteins (ABPs) are thought to be involved in the migration of neurons. Therefore, we have specifically analyzed the interacion of two of the MAP family members, MAP1B and LIS1, and its implication in neuronal migration. This interaction regulates the cellular motor dynein function. On the other hand, we have studied, why different strains of map1b-/- (NMR1 and C57/BL6) deficient mice develop different phenotypes .The resposible of these different phenotypes could be the existance of different genetic backgrounds. Thus, we have tested in two of these strains the concentrations of proteins that could complement the microtubule associated proein MAP1B function. In this study we have found a difference in the amount of microtubule associated EB1 proteín between towo of these strains.

Author: Valle Velasco Laura.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Centro Nacional de Investigaciones Oncológicas.
Place of preparation: CENTRO NACIONAL DE INVESTIGACIONES ONCOLÓGICAS.

Summary: The Cancer Colorrectal Hereditary Non Polipósico (CCHNP) is the syndrome susceptibility to colorectal cancer dominant inheritance more common and is characterized by the development of colorectal cancer, endometrial and other tumors at an early age. This syndrome is caused by germline mutations in a gene repair errors in DNA matching, and more than 90% of cases with CCHNP genetically defined is caused by mutations in the genes MLH1 and MSH2. The malfunctioning system repairer produces a phenotype mutador and accumulation of errors in microsatellites, called microsatellite instability (IMS). Due to the large size of the gene and the absence of hot spots of mutation, the study of molecular gene repair is costly both economically and time. For this reason and for the high occurrence of family aggregation of colorectal cancer, it is essential precise selection of candidates for the families molecular study. Currently, this selection are used: clinical criteria, Amsterdam, Bethesda, and any amendments thereto; the presence of IMS in the tumor tissue, and the immunohistochemical expression of the proteins encoded by genes repair. Results from studies that assess the selection criteria are contradictory, varying work to others, and are inconclusive. This fact makes it necessary to search for new approaches or markers, combined with previous ones, improve the selection process. In this paper have been evaluated and discussed the results of genetic studies conducted in 399 families with suspicion CCHNP and advised on the Consultation Cancer Family Council and the National Center for Genetic Research Oncológicas. The 28% of cases filed in the IMS tumor, considering only microsatellite BAT26, undetected greater sensitivity when using the "panel Bethesda." After the comprehensive study of the genes MLH1 and MSH2 in the IMS case, the 48% was carrying a disturbance at germ in one of these genes. It confirms that the hypermethylation monoalélica promoter MLH1 germ line is a mechanism for susceptibility to colorectal cancer and noted that mutations in the gene MSH6 appear to be rare in the Spanish population. Using immunohistochemical technique in tissue microarrays have been studied 271 tumors belonging to different families with suspicion CCHNP. The tumors are grouped according to the presence or absence of IMS; mutation in the gene repair, and as the presence of abnormal MLH1 or MSH2. We compared the characteristics relatives, clinics and inmunofenotípicas between groups defined tumors. In comparing the tumors with and without IMS it has been observed that the first group has a median age of onset earlier, a larger number of relatives with colorectal cancer and other cáncers associated with Lynch syndrome; more often proximal location of the tumor; better prognosis; loss of expression of proteins repair; overexpression of proteins related to the cell cycle: Ciclina A, D1, E and p16 and Skp2; highest rate of proliferation ki-67; overexpression of SMAD4, and lack expression of CK-20. Moreover, tumors without IMS presents more frequently overexpression of RAD50 and p53, and nuclear beta-catenin expression. Within the IMS group of tumors, in patients with germ-line mutation in one of the repair genes differ from those of the patients in whom no mutation was identified, which have a lower average age of onset; meet the most stringent criteria of CCHNP and show more frequent loss of expression of proteins repair and RAD50, and the presence of expression of Cdk2. The differences observed between tumors with germinal mutation in MLH1 and mutation in MSH2 are based principalmen 8 you in the 516 differential expression of proteins repair; in a higher rate of proliferation Ki-67 in tumors with mutation in MLH1; the increased frequency of tumors underwent changes in MLH1 with aberrant expression of beta-catenin, indicating that the path of Wnt is active in a high proportion of these tumors. In addition, we have identified three groups of tumors without IMS, or familiar with early onset, based on the expression profiles of immunohistochemical markers. Based on the results obtained in this paper we propose an action procedure for the selection of candidates families to studying gene repair.

Author: Sanchez Pulido Luis Fracisco.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Facultad de Ciencias Biologicas.
Place of preparation: Centro Nacional de Biotecnologia.

Summary: The work carried out in this thesis deals with the discipline of analysis of protein sequences, with the intention of showing homology relationships between them and the following definition of domains or regions conserved in multiple alignments of protein. Allowing this way in the establishment of functional similarity assumption among those proteins similar in sequence. Applying the analysis of sequences, the second tenet of the Method of Descartes: "Divide each of the challenges to consider, in this case protein sequences, in so many parts (domains) as possible and necessary to help solve" [Descartes, 1637 ]. We apply a common methodological approach to the analysis of different sequences of proteins in order to identify domains at dee sequence, assessing their conservation and distribution between different families of protein. With the main purpose of streamlining and interpret the similarity in terms of functional sequences common, such as interactions with other proteins or molecules, reaction mechanisms and / or overlapping regulation, and so on. We identified several domains in proteins linked to several human diseases, offering his way new insights for further characterization pilot.

Author: Esteras Chopo Alexandra.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Facultad de Ciencias.
Place of preparation: EUROPEAN MOLECULAR BIOLOGY LABORATORY.

Summary: Under certain circumstances normally soluble proteins lose their three-dimensional structure and deposited in the form of material known as insoluble fiber amiloides.Este process is associated with a number of human diseases such as Alzheimer's or Parkinson's, known as amiloidosis.Nuestra hypothesis is that they are working sequences short aminoaciados that determine the amilogeneicidad a proteina.Para prove this hypothesis we have carried out the conversion of a protein not amiloidogenica in a molecule capable of forming amyloid fibers through the insertion of hexapeptidos.Como protein model we chose the domain SH3 of espectrina, which does not form amyloid fibers under any of the conditions tested in our laboratorio.Como fragments amyloid we have selected one of the sequences designed de novo in the group, STVIIE highly amiloidogenica in vitro and a series of mutants puntuales.Las versions amiloidogenicas domain SH3 are as stable as the original protein fibers but are in a position in which the original domain remains soluble. Therefore the amiloigenicidad of these proteins is not due to a further destabilization due to insertions, but the properties amiloidogenicas of the inserted sequence. A potential strategy for the treatment of amyloidosis is the reversal of the process of formation of fibers amiloides.Puesto we have shown that short sequences are responsible for the beginning of the process of formation of fibers, our proposal is that molecules able to join the stream short amiloidogenica a protein should be effective to prevent the formation of intermediate or disassemble amyloid fibers maduras.Nuestra approximation for the development of these molecules is the use of D-peptidos.Como first target inhibition we have selected one of the sequences amiloidogenicas better characterized in the group STVIIE, 1.LA better secuncia for a D-inhibidor-1 has been determined using a peptidoteca positional type D. The effect of each D-aminoacido in each position of a D-hexapeptido linear in the inhibition of 1 was evaluated through Dicroismo CIrcular and Microscopy Electronica.BAsados in this deconvolucion, were synthesized and tested 32 D-peptidos sequence set against 1 . In this study we selected a set of molecules whose ability against inhibitory version amiloidogenica domain SH3 bearing the sequence 1,1-SH was probada.Mas of 60% of the molecules demostaron their effectiveness against this protein which confirms our hypothesis of trabajo.Del detailed study of 32 sequences also obtuivmos a set of empirical rules for the design of inhibitors peptidicos type D. These rules have been experimentally validated with the design of potentese inhibitors against secuenias amiloidogenicas short of peptide ABeta amyloid and the protein TAU.Estos D-peptidos designed according to the empirical rules are also specific to the amyloid short sequence for which they have been designed.

Author: DRAPER Y DÍAZ DE ATAURI ISABEL.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: It has conducted a survey biogeographic on briófitos epifitos of the four main systems montñosos of Morocco. Floristic The results obtained have been summarized in the catalog of brióftos epifitos, comprising a total of 93 taxa belonging to 22 families. In this catalog has been included data on the affinity of different taxa studied by the habitat, its ecology and its distribution in Morocco. The taxa more abundant and more frequently found in fruiting are epifitos usual, which constitute 32% of the total. The taxa indifferent and cortico-saxícolas, which are respectively 9% and 19% of the total are sometimes also are abundant and widely distributed by all mountain ranges, but generally are less frecentes. The taxa preferably not corticícolas, representing 39% of the total, tend to be rare in the stratum epifitos and be restricted to the basal layers of trees. This study has contributed to the knowledge of the brioflora territory studied first 13 appointments for North Africa and 6 first appointments to Morocco, in addition to providing numerous developments regional (7 for the Rif, 7 for the Middle Atlas, 13 for the High Atlas and 3 for Antiatlas). In addition, some of the localities prospectadas are locations represent the type or extension to Morocco area dstribución taxon recently proposed for Science, as is the case with Orthotrichum speciosum var. Brevisetum, O. Tortidontium and Zygodon catarinoi. The analysis of the distribution of briófitos epifitos in Morocco has highlighted significant differences between the mountain systems studied, both in terms of the rate of colonization habitat epifítico and in relation to the species richness and the number of taxa exclusive. The different representation of the various taxa in the territory has identified five types corológicos for briófitos epifitos of Morocco: "taxa widely distributed," "taxa from the Rif," "taxa from the Rif and the Middle Atlas," "taxa Atlas "and" taxa local presence. " As a result of a joint analysis of the organization and classification of localities have been able to describe five main types of communities brioepifíticas in Morocco: "communities Frullania dilatata of alcornocales of Ouezzane", "communities Fabronia pusilla of encinares Al Haddada , "" communities Orthtorichum lyellii of the Rif mountains and the Middle Atlas, "" communities Orthotrichum diaphanum of mountains domain Atlásico "and" communities Orthtorichum philibertii of encinares of Oulmés. " Three of these communities are in locations unique ecological conditions, which gives them a unique floristic composition in the territory of study. The other two are on the contrary widely distributed by Morocco and replaced gradually depending on the humidity. Finally, it has made a proposal of the areas of particular interest to the preservation of briófitos epifitos. This proposal is based on the criteria of species richness, the number of rare species, unique flora and representativeness of the regional flora. It proposes 17 areas of special concern, 8 in the Rif, 6 in the Middle Atlas, 2 in the High Atlas and one in the Antiatlas. These areas cover the most important aspects of the territory and it is believed that their protection would ensure a minimum retention of briófitos epifitos Moroccans.

Author: DÍAZ MUÑOZ LAURA.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: HOSPITAL GREGORIO MARAÑÓN.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: The vertical transmission of human immunodeficiency virus type 1 (HIV-1) is a serious problem worldwide. It has been estimated that approximately 1,600 children were infected each day. The transmission of the virus "in utero" occurs mainly through the placenta still unknown although the mechanism by which the placental cells are infected by HIV-1, in addition to its location and origin. On the other hand, cytokines and other maternal factors, such as progesterone, would be involved in the development and / or regulation of the placenta and the fetus as in regulating the replication of HIV-1. This report has sought to address some of these factors. First, it has been found that both the placental trophoblast cells as trophoblast cell lines are capable of being infected by different isolates of HIV-1, but with low efficiency. In these cell types express chemokines surface receptors, CXCR4 and CCR5, but not CD4 and HIV-1 appears that does not occur through these molecules. It should be noted that antibodies against B2-integrinas and LFA-1 are able to significantly block infection of T lymphocyte cells of the placenta. The surface expression of ICAM-1, molecule involved in the accession of lymphocytes to the barrier trophoblast, is increased in placentas infected with HIV-1 and these cells will transfer the infection to T lymphocytes For this to happen it is necessary to contact transmission cell is inhibited by antibodies anti -- LFA-1. The results suggest that the placental trophoblast cells can be infected by HIV-1 through a mechanism with the participation of the contact between the placenta T lymphocytes. Moreover, the infection in cells of the placenta produces increased the expression of ICAM-1 and leukocyte adhesion, an event that is required to transfer the infection of HIV-1. This could somehow explain how vertical transmission occurs through the placental barrier. Progesterone is increased at the interface fetoplacentaria during pregnancy. So far, no known the possible role of this hormone in the vertical transmission of HIV-1. In vitro experiments resulted in an inhibition of the replication of HIV-1 in trophoblast cells and purified trophoblast cell lines, the concentration that is found in the placental interface. In addition, progesterone that inhibit replication in a way post-entrada. Surprisingly, progesterone does not produce or basal-induced inhibition of transcription LTR or nuclear factor kappa-B (NF-kB) in these cells. To this must be added that the synthesis of TNF in placental cells is induced by infection with HIV-1, which will result in the activation of viral replication, neutralized by anti-TNF antibody. The progesterone inhibits the induction of transcription TNF due to the virus or gp120. Therefore, the results suggest that progesterone inhibits the replication of HIV-1 in placental cells by reducing the levels of TNF, which are required for a good viral replication. The mechanism by which the progesterone inhibits transcription of TNF should be studied in more depth and seem to have no place via inhibition of transcription factors NF-kB, NF-AT or AP-1.

Author: Viera Vicario Alberto.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Facultad de Ciencias.
Place of preparation: Facultad de Cencias, Dpto. Biología UAM.

Summary: From a cytological "telómero" is used to identify the physical end of the chromosomes of linear eukaryotic organisms. In this domain is contained chromosomal DNA telomérico in mammals consists of a variable number of tandem repeats in the sequence TTAGGG, as well as various specific proteins associated forming the so-called "complex teloméricos." In this thesis has tried to help not only the knowledge of the structure, composition and location of the complex teloméricos during meiosis, but also provide new data regarding changes morfofuncionales they experienced during the two meiotic divisions. The experimental model used has been laboratory mice (Mus musculus) by submitting all chromosomes telocéntricos, ie at the end of all chromosomes centromérico complexes teloméricos proximal are in the regions of heterocromatina centromérica. This peculiarity has been that this is a kind of choice for that particular conformation during the first meiotic division to be introduced regions centroméricas such chromosomes. Thus, in metaphase I, cinetocoros brothers should be directed to a single pole cell, so that the presence of the complex teloméricos in these areas would be a hindrance estérico for correct interaction of spindle microtubules with cinetocoros. It has sought to identify and analyze possible differences in the length of the repetitions teloméricas in condensed chromosomes during the two meiotic divisions of male mouse using fluorescent in situ hybridization (FISH) with a probe telomeric (C3TA2) 3 péptidonucleica (PNA). The reultados show heterogeneity in the number of repetitions of DNA telomérico between different complement of chromosomes, chromosome counterparts among and even within a single chromosome. Likewise, there are many proteins whose functions described are essential to the proper functioning and the structure of telomeres in the chromosomes mitóticos. Therefore, it has been analyzed by immunofluorescence its appearance, location and dynamics in the complex teloméricos during meiotic divisions mouse spermatocytes. Additionally, their relationship has been studied with various proteins centrómero / Kinetochore, and the protein component side of the complex sinaptonémico SYCP3. The results show that the complex teloméricos, contrary to what occurs during prophase I, are not located in the extreme físco of chromatids of chromosomes condensed. Consequently, the structure of chromosome meiótico must change from paquitene until metaphase I, suggesting that the complex teloméricos range until their relocation in condensed chromosomes. Moreover, it has obsevado that the complex proximal telomérico fall below the cinetocoros from metaphase I until anafase II. It has also analyzed the presence of the protein RAD51D, a recombinasa which has recently been identified in the complex teloméricos of somatic line. Our results show that RAD51D appears associated with the complex teloméricos along the two meiotic divisions, and propose a model for their association with them. It has been studied for the first time in vertebrate the presence and location of the subunits of complex condensina I during meiosis. The results showed that this protein complex appears in the nuclei of spermatocytes in the prophase I localizándose in the nucleoli. Likewise, for the first time shows the relative distribution of complexes condensina I and cohesina in stickers 8 omas of b5a mouse along meiosis. Additionally, there has been silver impregnation of chromosomes meióticos condensate, with the aim of displaying their axes cromatídicos. The results obtained show that these shafts are diponen in the central region of the chromatids at metaphase I, showing a pattern of dsitribución very similar to the complex condensina I. As a culmination of this study has analyzed the distribution of complex teloméricos in a genetically altered mouse model, which presents severe alterations of spermatogenesis, in order to compare it with that of the control mice. Have been selected for this knockout mice for kinase-dependent ciclina CDK2, as this protein, with important implications for the regulation of the cell cycle, has been identified in the complex teloméricos mouse during prophase I. While to date is not known the role of CDK2 in the complex teloméricos, meiosis in his absence means that the complex teloméricos not join the nuclear envelope during prophase I. It has also detected the existence of phenomena synapses not homologous and mergers between different ends of chromosomes. All these disorders culminate with the entry into apotosis of spermatocytes, which do not exceed the strict control point of paquitene are eliminated, so that these individuals are azoospermia. Finally, we discuss the possible origin of the variability in the length of DNA telomérico in the germ line, the functional significance of the relocation of the complex teloméricos in chromosomes meióticos condensates and the possible implications of RAD51D in maintaining the structure of the complex teloméricos. It proposes a model conciliator of the organization and layout of the complex teloméricos in the domain of telómero in cytological chromosomes meióticos condensates, which collects the data obtained during the execution of this thesis. It also presents a model on how to operate the structural changes experienced by mammalian chromosomes along meiosis placing special emphasis on the distribution of the axes cromatídicos and complex teloméricos each stadium meiótico.

Author: Carrasco Rando Marta.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Centro de Biología Molecular Severo Ochoa.
Place of preparation: Centro de Biología Molecular Severo Ochoa.

Summary: The muscles of Drosophila and vertebrate syncytical fibers are formed by fusion of myoblasts. The merger process is asymmetric and is preceded by the subdivision of mesodermo in subtypes of myoblasts: founders and competent merger. The founders contain the information necessary for the development of different specific muscles and are the only ones able to complete miogénesis in the absence of merger. The relevant merger are attracted by the founders being recruited to their specific patterns of gene expression through the merger process. Thus, in addition to the gene expression programs specific type of muscle, the founders share a number of characteristics properties population, as the attraction of the merger or myoblasts competent in the formation of apodemas (tendons). In order to study these properties as specified, we initiated the functional characterization of gene expression restricted to the various subpopulations. This is the case of gene CG17492, which we named musculus morbidus (mumo). Mumo encodes for a protein E3 ubiquitín ligasa whose function is essential for miogénesis of Drosophila melanogaster. Thus, in mutant embryos for mumo takes place the initial formation of a muscle correct pattern, indicating that neither the segregation nor the specification of the founders myoblasts is altered in these embryos. However, present defects of differentiation which are reflected in early failures in the process of merging somatic musculature and morphological problems in the visceral muscles. In addition, the contractile activity that occurs at the end of embryonic development has resulted in the destabilization of the bands of miofibrillas Z and the consequent removal of the fibers of the tendon leading to mioesferas. Therefore, the data collected in this study show that Mumo is necessary for the proper maintenance of the integrity of the band Z in larval muscles, as well as to stabilize its anchorage to the epidermis. In addition, we found that the lack of function mumo produces the same phenotype in the adult muscle fibers, which accumulates in the banza Z. Again in these fibers, Mumo is necessary to maintain the integrity of sarcomere. We have also shown that Mumo is E3 ubiquitín ligasa responsible for the synthesis of Artrina, a stable of Actina mono-ubiquitinada which is part of the fine filament of indirect flight muscles. However, our data support the idea that the lack of production Artrina is not the only factor responsible for the observed phenotype, suggesting that either Mumo is acting on other substrates, or Mumo has additionally a structural role in the sarcomere.